\r\n\t• Role of technological innovation and corporate risk management \r\n\t• Challenges for corporate governance while launching corporate environmental management among emerging economies \r\n\t• Demonstrating the relationship between environmental risk management and sustainable management \r\n\t• Contemplating strategic corporate environmental responsibility under the influence of cultural barriers \r\n\t• Risk management in different countries – the international management dimension \r\n\t• Global Standardization vs local adaptation of corporate environmental risk management in multinational corporations. \r\n\t• Is there a transnational approach to environmental risk management? \r\n\t• Approaches towards Risk management strategies in the short-term and long-term.
",isbn:"978-1-83968-906-2",printIsbn:"978-1-83968-905-5",pdfIsbn:"978-1-83968-907-9",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!1,hash:"9b65afaff43ec930bc6ee52c4aa1f78f",bookSignature:"Dr. Muddassar Sarfraz and Prof. Larisa Ivascu",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/10226.jpg",keywords:"Global Risk Management, Risk Assessment, Climate Risk, Environmental Management, International Business, Business Sustainability, Corporate Governance, Financial Market, Financial Risks, Sustainable Economic Environment, Business Valuation, Organizational Behavior",numberOfDownloads:131,numberOfWosCitations:0,numberOfCrossrefCitations:0,numberOfDimensionsCitations:0,numberOfTotalCitations:0,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"September 24th 2020",dateEndSecondStepPublish:"October 22nd 2020",dateEndThirdStepPublish:"December 21st 2020",dateEndFourthStepPublish:"March 11th 2021",dateEndFifthStepPublish:"May 10th 2021",remainingDaysToSecondStep:"4 months",secondStepPassed:!0,currentStepOfPublishingProcess:4,editedByType:null,kuFlag:!1,biosketch:"Dr. Muddassar Sarfraz focuses on corporate social responsibility, human resource management, strategic management, and business management. He is a member of the British Academy of Management (UK), Chinese Economists Society (USA), World Economic Association (UK), American Economic Association (USA), and an Ambassador of the International MBA program of Chongqing University, PR China, for Pakistan.",coeditorOneBiosketch:"Dr. Larisa Ivascu's area of research includes sustainability, management, and strategic management. She has published over 190 papers in international journals. She is vice-president of the Society for Ergonomics and Work Environment Management, Timisoara, and a member of the World Economics Association (WEA), International Economics Development and Research Center (IEDRC), Engineering, and Management Research Center (CCIM).",coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"260655",title:"Dr.",name:"Muddassar",middleName:null,surname:"Sarfraz",slug:"muddassar-sarfraz",fullName:"Muddassar Sarfraz",profilePictureURL:"https://mts.intechopen.com/storage/users/260655/images/system/260655.jpeg",biography:"Dr Muddassar Sarfraz is working at the Binjiang College, Nanjing University of Information Science and Technology, Wuxi, Jiangsu, China. He has obtained his PhD in Management Sciences and Engineering from the Business School of Hohai University. He holds an International Master of Business Administration (IMBA) from Chongqing University (China) and Master of Business Administration (HR) from The University of Lahore. He has published tens of papers in foreign authoritative journals and academic conferences both at home and abroad.\nHe is the Book Editor of Sustainable Management Practices, Analyzing the Relationship between Corporate Governance, CSR, Sustainability, and Cogitating the Interconnection between Corporate Social Responsibility and Sustainability. He is the Associate and Guest Editor of Frontiers in Psychology, International Journal of Humanities and Social Development Research and the Journal of Science and Innovative Technologies. He is an Editorial Board Member of the International Journal of Human Resource as well as a member of the British Academy of Management (UK), Chinese Economists Society (USA), World Economic Association (UK), American Economic Association (USA), and an Ambassador of the International MBA program of Chongqing University, PR China, for Pakistan. \nHis research focuses on corporate social responsibility, human resource management, strategic management, and business management.",institutionString:"Binjiang College, Nanjing University of Information Science &Technology, Wuxi, Jiangsu",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"1",institution:null}],coeditorOne:{id:"288698",title:"Prof.",name:"Larisa",middleName:null,surname:"Ivascu",slug:"larisa-ivascu",fullName:"Larisa Ivascu",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRfMOQA0/Profile_Picture_1594716735521",biography:"Dr Larisa IVAȘCU is currently an associate professor at the Politehnica University of Timisoara. 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From chapter submission and review, to approval and revision, copyediting and design, until final publication, I work closely with authors and editors to ensure a simple and easy publishing process. I maintain constant and effective communication with authors, editors and reviewers, which allows for a level of personal support that enables contributors to fully commit and concentrate on the chapters they are writing, editing, or reviewing. I assist authors in the preparation of their full chapter submissions and track important deadlines and ensure they are met. I help to coordinate internal processes such as linguistic review, and monitor the technical aspects of the process. As an ASM I am also involved in the acquisition of editors. 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Glycine receptors (GlyRs) belong to the Cys-loop ligand-gated ion channel (LGIC) family, a group of membrane ion channel receptors including γ-aminobutyric acid type A (GABAA), neuronal nicotinic acetylcholine (nACh), 5-HT3, and GlyRs. These receptors are critical for fast synaptic neurotransmission in the central nervous system. GlyRs are known to predominantly mediate fast synaptic inhibitory neurotransmission in the spinal cord and brain stem [1]. To date, four GlyRs subunits have been identified in humans including three α subunits (α1–3) and one β subunit [1]. The α subunits share a high degree of homology in the amino acid sequence (>90%), especially in the large extracellular domain that bears agonist- and antagonist-binding sites. This has posted a challenge to the development of selective ligands for specific GlyR subunits. Two very recent studies have resolved crystal structures of GlyRα1 and α3 subunits with high level of resolution (3.0 A) [2, 3]. These studies have detailed the molecular insights of GlyR-agonist/antagonist interaction and channel-gating dynamics.
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It is well established that GlyR β subunits are expressed at postsynaptic sites where they can assemble with the α subunit to form heteromeric functional channels [4]. A cytoskeleton protein, gephyrin, plays a critical role in targeting heteromeric GlyRs at postsynaptic sites. While the GlyRs represent the primary inhibitory neurotransmission in spinal cord, the role of GlyRs in most supraspinal areas has been less clear [5, 6]. Although the β subunit mRNA is relatively abundant in all brain areas at the adult stage, the β subunit protein expression in many brain regions appears very low for an unknown mechanism [5]. Coincidently, glycinergic synaptic transmission in all brain areas except the spinal cord and brain stem are nearly absent at the adult stage [1]. While the α2 subunit represents the dominant form of GlyRs at early development stage, it gives way to the α1 subunit after postnatal stage [7, 8]. The α1β subunits are found to serve as the dominant functional form of GlyRs in the spinal cord and brain stem at the adult stage [9]. The biological switch between the α1 and α2 subunits occurs at a time point of ~postnatal 16–20 days [6, 10]. This timing is consistent with a shift from GABAergic to glycinergic transmission representing the maturity of brain stem and spinal inhibitory systems [6, 10]. In some brain areas such as forebrain and hippocampus, however, the mRNA levels of the α2 subunit remain to be at the steady state from developmental to adult stage [11–15]. Distinct expression of GlyR subunits is consistent with their physiological and pathological roles. For instance, the α3 subunits are restrictively expressed in the superficial layers of the spinal cord dorsal horn, consistent with the involvement of their role in the regulation of nociceptive process [16]. On the other hand, the dominant expression of GlyRα1 subunits in spinal cord and brain stem motor neurons explains well how the functional deficiency in the α1 subunits can cause human hyperekplexia disease, a neuromotor disorder [17, 18].
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2. Presynaptic and extrasynaptic GlyRs
\n
While postsynaptic GlyRs have been the major interest of many previous and current studies [1], evidence has emerged to suggest that functional GlyRs are also located at presynaptic terminals and extrasynaptic sites in many brain areas [19–25].
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2.1. Presynaptic receptors
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Presynaptic GlyRs are first described in calyceal synapses in the medial nucleus of the trapezoid body (MNTB) in rat brainstem [19]. These receptors are thought to play an important role in the modulation of glutamate release [6, 10, 23, 26]. Presynaptic GlyRs have also been reported from studies of other brain areas such as spinal cord, ventral tegmental area (VTA), hippocampus and periaqueductal gray area (PAG), and brain stem hypoglossal nucleus [22, 24, 25, 27, 28].
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Presynaptic GlyRs are believed to regulate releases of major neurotransmitters including GABA, DA, and glutamate. All three α [1–3] subunits have been identified to contribute to presynaptic glycinergic activity in different brain regions. While the α2 subunits mediate the facilitation of presynaptic GABAergic transmission in VTA at early development stage [20], the α1 subunits emerge and facilitate glutamate release at presynaptic sites of brain stem calyx in the postnatal stage [6, 26]. A very recent study has shown that the α3 subunits are involved in presynaptic glycine release in brain stem hypoglossal motor neurons [25].
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Different from postsynaptic heteromeric GlyRs, presynaptic GlyRs are the likely homomeric α subunits [23, 27, 28]. There are a number of evidence to support this idea. First, the β subunit is always bound with postsynaptic cytoskeleton protein, gephyrin [4, 29]. Second, low concentrations of picrotoxin (PTX) that are found to preferentially inhibit homomeric α GlyRs in vitro selectively alter presynaptic GlyR functionality in the spinal cord and brainstem [23, 27, 30–33]. Finally, this idea is consistent with microscopic observation that the GlyRs at presynaptic terminals of calyceal synapses are composed of homomeric α1 subunits [23]. The presynaptic GlyRs have been the interest of recent research because they disinhibit GABA-mediated synaptic inhibition of VTA dopaminergic neurons [20, 34]. There is evidence suggesting that these receptors are involved in the reward mechanism of drugs of abuse [34].
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Presynaptic GlyRs are a potential therapeutic target for the treatment of hyperekplexia disease [26]. A very recent study has shown that streptozotocin-induced diabetic nerve injury caused a decrease in the paw withdrawal latency to mechanical stimuli and reduced the mean frequency of glycinergic miniature inhibitory post-synaptic current (mIPSC) in spinal dorsal horn neurons [35]. This effect is selectively mediated through a presynaptic mechanism because there is no change in miniature inhibitory post-synaptic current rise, decay kinetics, and mean mIPSC amplitude following streptozotocin injection.
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2.2. Extrasynaptic GlyRs
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Extrasynaptically located GlyRs have been identified in many brain regions, including hippocampus, supraoptic nucleus, and prefrontal cortex (PFC) [13, 36–39]. Functional extrasynaptic GlyRs are likely α homomers because clustering and synaptic targeting of GlyR β subunit requires postsynaptic protein gephyrin [4]. The endogenous agonists of nonsynaptic GlyRs have been postulated to be glycine and taurine [37, 39–41]. While glycine is originated from either synaptic spillover or via release from glia [39, 42], taurine is released from glial cells where the synthesizing enzyme and the transporter for taurine are present [40, 43–45]. Taurine can be released in high levels in response to physiological and pathological conditions. For instance, taurine is released in response to hypotonic stimulus [46]. There is strong evidence to suggest that ethanol can promote the release of taurine in mesolimbic structure [47–49]. The biological role of tonic activation of extrasynaptic GlyRs remains elusive. Accumulating evidence has suggested that these extrasynaptic GlyRs are likely the target for ethanol modulation in vitro and in vivo [48, 50, 51].
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Although our knowledge about presynaptic and extrasynaptic GlyRs is still limited, these receptors could represent emerging targets attractive for future mechanistic and therapeutic studies.
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3. GlyR-related disease
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3.1. GlyRs in chronic pain
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The GlyRs mediate fast synaptic inhibitory neurotransmission and regulate pain formation at spinal level. The α3GlyRs are thought to be the key player involving in spinal antinociceptive process [16, 52].
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3.1.1. α3GlyRs in inflammatory pain
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α3GlyR knockout mice demonstrate a reduction in pain hypersensitivity in several lines of chronic pain models. Prostaglandin E2 (PGE2), which promotes central and peripheral pain sensitization, selectively inhibits α3GlyRs channel activity through the activation of receptor phosphorylation in vitro [16]. Consistent with this, PGE2 inhibits the glycinergic inhibitory postsynaptic currents in spinal cord slices of wild type (WT), but not in α3GlyRs knockout mice [16]. These α3 knockout mice reduce thermal hyperalgesia induced by the intrathecal injection of PGE2 [16, 52]. PGE2 inhibition of the α3GlyRs is attributed to the mechanism of chronic inflammatory pain induced by the intra-plantar injection of complete Freund’s adjuvant (CFA) [16, 52]. The α3GlyRs are not involved in all inflammatory pain animal models. While the α3GlyR knockout mice show reduced pain hypersensitivity to spinal PGE2 injection and CFA- or zymosan-induced peripheral inflammation, these mice do not display altered pain hypersensitivity after the injection of capsaicin, carrageenan, kaolin/carrageenan, or monosodium iodoacetate, which produces rheumatoid and osteoarthritis [53]. A very recent study suggested that glucose at 5 mM can allosterically increase α3GlyR receptor activity, and this interaction between the α3 subunit and sugar may underlie some of the analgesic effects of glucose [54].
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3.1.2. α3GlyRs in neuropathic pain
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Similarly, the α3GlyRs are also found to play a selective role in some forms of neuropathic and visceral pain models. For instance, there is no significant difference in pain behaviors between α3GlyR knockout mice and wild-type littermates following partial sciatic nerve ligation and colorectal distension [53]. On the other hand, evidence is also available suggesting that these receptors are involved in some forms of neuropathic pain models. For instance, there is a substantial reduction in the frequency of GlyR-mediated mIPSC of lamina I neurons in rat diabetic neuropathic pain after treatment with streptozotocin in rats [35]. Intrathecal injection of glycine reverses streptozotocin-induced tactile pain hypersensitivity. Moreover, the intrathecal injection of α3GlyR siRNA can reduce the anti-allodynia effect of platelet-activating factor antagonists in three different nerve injury animal models including partial sciatic nerve ligation injury, streptozotocin-induced diabetic nerve injury, and infraorbital nerve injury [55]. Overall, these data indicate that the α3GlyRs are involved in the mechanism of neuropathic pain pathway.
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The role of the α2GlyR subunit in antinociception is unclear. A previous study has reported that the mice lacking the α2 subunits showed prolonged mechanical hyperalgesia induced by the peripheral injection of zymosan [56]. The α2 subunits are unlikely to play a role in persistent neuropathic pain (partial sciatic nerve ligation) as the mice lacking either α2 subunit demonstrated a normal nociceptive behavior after spinal nerve injury [56]. So far, the α1GlyRs have not been reported to play any role in pain modulation [57].
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Taken together, the α3GlyRs have been the interest of many research interest because of their unique role in nociceptive process and their therapeutic potential in the development of new anti-pain drugs [52, 58–60].
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3.2. Alcohol use disorder
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Several lines of studies have provided consistent evidence to suggest that GlyRs are one primary target that mediates alcohol-induced behaviors in the brain [61–65]. Activation of VTA GlyRs reduces GABAergic transmission and increases the activity of dopaminergic neurons originated from VTA [20, 34]. GlyRs in the nAc are involved in modulating both basal- and ethanol-induced dopamine output in the same brain region as local injection of strychnine can inhibit ethanol-induced DA release in nAc [48, 66]. There is strong evidence that extrasynaptic GlyRs are the candidate that, at least in part, mediates ethanol-induced dopamine elevation and reward system in nAc [49, 51, 67, 68]. These receptors are likely activated by taurine, which is released from glial cells upon exposure to ethanol [49]. Microinjection of glycine into the VTA reduced the intake of ethanol in rats chronically exposed to ethanol under the intermittent-access and continuous-access procedures and decreased lever-press responding for ethanol under an operant self-administration procedure [69]. VTA microinjection of strychnine completely reversed glycine inhibition of alcohol consumption behaviors, suggesting that GlyRs in the VTA may play a critical role in ethanol self-administration in animals [69]. Consistent with this idea, a recent study in α2- and α3GlyR knockout mice has shown that the depletion of the α2GlyRs decreased ethanol intake and preference in the 24-h two-bottle choice test, whereas the depletion of the α3GlyRs increased ethanol intake and preference in the 24-h intermittent access test [70]. It appears that these GlyR subunits are selectively involved in ethanol consumption behavior but not acute ethanol intoxication-induced behaviors such as motor incoordination, loss of righting reflex, and acoustic startle response [70]. By contrast, mice carrying knock-in mutations in the GlyR α1 subunit alter the behaviors induced by acute ethanol intoxication [71, 72]. Thus, the α2- and α3GlyR subunits are involved in the reward mechanism of chronic ethanol consumption, while α1GlyR subunits are attributed to acute alcohol intoxicating-induced behaviors.
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3.3. Rare genetic disease: hyperekplexia
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Human exaggerated startle disease, also known as hyperekplexia, is a rare genetic neurological disorder caused by deficiency in glycinergic neurotransmission [73]. Missense point mutations in the human GlyRs α1 subunit gene disrupt GlyRs function resulting in familial startle disease, an autosomal-dominant disorder [74, 75]. Although rare, this disease is often characterized by an exaggerated startle reaction to sudden, unexpected auditory and tactile stimuli. The most frequently occurring mutation causing human hyperekplexia is the R271Q/L mutation in the α1 subunit [75]. Mice carrying the R271Q mutation exhibit severe neuromotor defects that resemble human hyperekplexia disease [57]. Except for the mutations occurring in the GlyR α1 subunit, point mutations in the GlyR β subunit are also linked to recessive human hyperekplexia disease [76].
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4. Cannabinoid interaction with GlyRs
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4.1. Cannabinoid potentiation of GlyRs
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4.1.1. Allosteric modulation
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A previous study from our laboratory has shown first evidence that both exogenous and endogenous cannabinoids such as ∆9-tetrahydrocannabinol (THC), the principle psychoactive component of marijuana, and endocannabinoid anandamide (AEA) potentiate the amplitude of glycine-activated current (I\nGly) in cells expressing homomeric α1 and heteromeric α1β GlyRs and in acutely isolated VTA neurons [77]. The modulation by cannabinoids is not dependent on CB1 receptors. This initial finding has been tested and supported by a number of studies [58, 78–82]. The EC50 values for the THC-induced potentiation are 73 nM for human α1GlyRs, 109 nM for human α1β GlyRs expressed in Xenopus oocytes, and 320 nM for native GlyRs in rat VTA neurons [83]. THC at low concentrations of 100 and 300 nM can significantly enhance I\nGly in HEK-293 cells expressing the α1 and α3 subunits [58]. This concentration range of THC has been found to induce psychotropic and antinociceptive effects in humans [84]. The concentrations of THC in human blood can peak as high as 800 nM for 15 min after a casual marijuana inhalation and stay at 100 nM for 60 min after the smoke. The potentiation of I\nGly by either exogenous or endogenous cannabinoids depends on the concentration of glycine [58, 78, 81–83]. Maximal potentiation of GlyRs induced by cannabinoids occurs at the lowest concentration of glycine. With increasing glycine concentrations, the cannabinoid potentiation decreases [83].
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4.1.2. Subunit-specific modulation
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Both endogenous and exogenous cannabinoids modulate GlyRs in a subunit-specific manner [58, 78, 81, 82]. AEA has been found to produce various effects on I\nGly in different neurons [82, 83, 85]. Among all three GlyRs α subunits (α1, α2, and α3) expressed in HEK-293 cells, the α1 subunit is most sensitive to AEA-induced potentiation [78, 81, 82]. In addition to AEA, other cannabinoids and cannabinoid-mimic lipids such as N-arachidonyl-glycine (NA-glycine) exhibit complex action (both potentiation and inhibition) of I\nGly in a subunit-specific manner [81]. NA-glycine potentiated the amplitude of I\nGly in HEK-293 cells expressing the α1 subunits and inhibits the amplitude of I\nGly in HEK-293 cells expressing the α2 and α3 subunits [81]. Similarly, THC has been shown to potentiate GlyRs in a subunit-specific manner expressed in HEK-293 cells [58]. The most significant difference among the three subunits appears to be the efficacy of the THC potentiation [58]. For instance, the magnitudes of the THC (1-μM)-induced potentiation of I\nGly are 1156, 1127, and 232% in HEK-293 cells expressing the α1, α3, and α2 subunits, respectively. It should be mentioned that heteromeric α1β1 subunits are less sensitive than their counterpart homomeric α1 receptors to THC-induced potentiation [58, 83]. This is also the case that DH-cannabidiol (CBD), a modified cannabidiol, selectively rescues the function of mutant homomeric α1GlyR subunits [26].
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4.2. Molecular mechanisms
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4.2.1. Direct interaction and the site
\n
The α1, α2, and α3GlyR subunits are differentially sensitive to THC- and AEA-induced potentiation of I\nGly [58]. Molecular analysis has identified single amino acid residue, serine (S), in the TM3, the α1 and α3 subunits critically involved in cannabinoid-GlyR interaction [58, 82]. Substituting the serine (S) at 296 of the α1 subunit and at 307 of the α3 subunit with an alanine (A) converts the α1/α3 subunits from cannabinoid high-sensitive receptors to cannabinoid low-sensitivity receptors. This suggests that S296 is a molecular determinant of cannabinoid potentiation of GlyRs. This idea has gained support from an experiment involving nuclear magnetic resonance (NMR) chemical shift measurement [58]. THC selectively shifts the S296 residue in a concentration-dependent manner in the purified proteins of the full-length four TMs of the human α1 subunit. This hypothesis is further tested by NMR titration and nuclear Overhauser effect spectroscopy (NOESY) analysis of the interaction between cannabidiol and purified α3GlyR protein. The data from these experiments favor a direct interaction of cannabidiol with residue S296 of the GlyR α3 subunit. The analysis of the α3GlyR transmembrane (TM) domains indicates that S296 is located near the intracellular end of the TM3 helix. Direct interaction of CBD with α3GlyR-TM protein is confirmed by the intermolecular NOESY cross-peaks between CBD and the protein. This finding also favors a protein conformational change at S296 in the presence of CBD.
\n
Electrophysiological experiments using mutagenesis analysis indicate a hydrogen-bonding interaction between cannabinoid and S296 residue [58, 86]. Consistent with this idea, chemically the removal of both hydroxyl and oxygen groups from THC abolishes the efficacy of THC in potentiating GlyRs [58]. However, the compound with retaining oxygen group is still potent in potentiating GlyR function but demonstrates significantly reduced binding affinity to CB1 receptors.
\n
\n
\n
4.2.2. A common molecular basis for endogenous and exogenous cannabinoids
\n
It has been proposed that exogenous and endogenous cannabinoids potentiate GlyRs via a common molecular basis. This idea is based on the following evidence. First, the point mutation at the S296 residue in the TM3 is critical for both THC and AEA potentiation of the α1 and α3 subunits [58, 83, 86]. Second, the hydroxyl/oxygen groups are essential for AEA and THC potentiation of GlyRs. Third, the deletion of these groups results in reduction in the efficacy of AEA and THC potentiation. Finally, desoxy-AEA and didesoxy-THC are found to inhibit AEA- and THC-induced potentiation of GlyRs in a similar manner.
\n
\n
\n
\n
\n
5. Therapeutic potential of glycinergic cannabinoids
\n
\n
5.1. Suppression of acute and chronic pain by targeting α3GlyRs
\n
One popular medical benefit from the use of cannabis is its therapeutic relief of chronic pain. There is evidence showing that some of the THC-induced cellular and behavioral effects are independent of CB1 receptors.
\n
\n
5.1.1. α3GlyR dependent
\n
A previous study has shown that the THC-induced analgesic effect in tail-flick reflex (TFR) test remained unchanged in CB1 and CB1-CB2 double-knockout mice, suggesting a different target that may mediate THC analgesia [87]. In view of this observation, we tested whether or not GlyRs are involved in the THC-induced analgesia in the TFR. Both THC and 5-desoxy-THC, a nonpsychoactive cannabinoid, produced a strong analgesic effect in TFR test, and this effect was completely abolished by the administration of strychnine. Cannabinoid-induced analgesic effect was completely absent in the α3GlyR knockout mice. By contrast, the analgesic effect induced by THC remains unchanged in both CB1 and α2GlyR subunit knockout mice [58]. The THC-induced hypothermia did not significantly differ between the α3GlyR knockout and wild-type mice. While 5-desoxy-THC is analgesic, it does not significantly affect locomotor activity and body temperature of mice. Collectively, these data have provided first evidence that α3GlyRs are the target that selectively mediates some of cannabinoid analgesic effects.
\n
The α3GlyRs contribute to the mechanism of chronic inflammatory pain induced by the intra-plantar injection of complete Freund’s adjuvant [16, 53]. Intrathecal injection of cannabidiol, the major nonpsychoactive component of cannabis, and DH-CBD, a chemically modified CBD, suppress pain hypersensitivity following CFA intra-plantar injection [52]. In addition, DH-CBD significantly attenuates both mechanical and heat-induced pain hypersensitivity following spinal sciatic nerve ligation [52]. Both DH-CBD- and CBD-induced analgesic effects in CFA-induced pain hypersensitivity were significantly reduced in mice lacking the α3 subunits. On the other hand, CBD- and DH-CBD-induced analgesic effects remained unchanged in either CB1 or CB2 knockout mice as compared to their WT littermates.
\n
\n
\n
5.1.2. A correlation between cannabinoid potentiation of I\nGly and cannabinoid analgesia
\n
To explore the interrelationship between cannabinoid in vitro and in vivo effects, 11 synthetic cannabinoids structurally similar to CBD were collected and their structural and functional activity was evaluated. Overall, there is a strong correlation between the cannabinoid-induced potentiation of GlyRs and cannabinoid-induced analgesic effect in chronic inflammatory pain in mice. By contrast, there is no such interrelationship between cannabinoid-induced analgesia and cannabinoid-binding affinity for either CB1 or CB2 receptors. Neither cannabinoid-induced potentiation of GlyRs nor cannabinoid-induced analgesia is significantly correlated with cannabinoid-induced psychoactive effects such as hypothermia, hypolocomotion, and incoordination. Collectively, these data suggest that cannabinoids selectively target at α3GlyRs to produce some of the analgesic effects.
\n
\n
\n
\n
5.2. Rescue of hyperekplexia by targeting presynaptic α1GlyRs
\n
Despite overwhelming evidence for functional deficiency of GlyRs in hyperekplexia disease, current therapeutic agents do not target GlyRs [88]. While postsynaptic GlyRs as α/β heteromers attract the most research attention, little is known about the role of presynaptic GlyRs, likely α homomers, in diseases. Therefore, two testable questions emerge. Can DH-CBD treat exaggerated startle response by restoring deficiency in GlyR function? What is the role of presynaptic α1GlyRs in hyperekplexia disease?
\n
\n
5.2.1. Cannabinoid restoration of exaggerated startle response
\n
DH-CBD, in a concentration-dependent manner, rescued the functional deficiency caused by α1R271Q-mutant GlyRs expressed in HEK-293 cells in spinal neurons isolated from α1R271Q-mutant mice [26]. Intraperitoneal injection of DH-CBD at 10–50 mg/kg suppressed both acoustic noise and tactile-induced exaggerated reflex displayed in α1R271Q-mutant mice. Similarly, DH-CBD restored a hind feet-clenching behavior and exaggerated tremor when picked up by the tail demonstrated in these hyperekplexia mice. 9 hyperekplexic-mutant α1GlyRs are classified as cannabinoid-sensitive and -insensitive receptors based on their response to cannabinoid potentiation of I\nGly and rescue of startle behavior. A correlational analysis was conducted between DH-CBD potentiation of mutant GlyR function and DH-CBD therapeutic efficacy of 4 hyperekplexia-mutant α1GlyR knock-in mice. The efficacy of DH-CBD rescue of GlyR function is correlated with its restoration of exaggerated startle behaviors. This suggests that DH-CBD restoration of hyperekplexic-mutant receptors and mice appears to be a site/genotype-specific effect.
\n
\n
\n
5.2.2. Therapeutic potential of presynaptic GlyRs
\n
There is strong evidence to suggest that presynaptic GlyRs are a potential therapeutic target of dominant hyperekplexia disease [26]. First, hyperekplexic point mutations in the α1 subunits disrupted the function of homomers more significantly than that of heteromers when expressed in HEK-293 cells. Consistent with this, the hyperekplexic mutation was found to preferentially impair I\nGly recorded in presynaptic terminals but not that from postsynaptic sites of calyceal/MNTB synapses. Second, hyperekplexic-mutant homomers were more sensitive than heteromers to DH-CBD-induced rescue. Third, DH-CBD potentiated presynaptic homomeric α1GlyRs without significantly altering postsynaptic GlyR activity recorded in calyx slices isolated from hyperekplexic-mutant mice. In line with this observation, DH-CBD preferentially restored the diminished frequencies of Gly sIPSCs and mIPSCs, whereas DH-CBD did not significantly alter the amplitudes of Gly sIPSCs and mIPSCs in spinal cord slices from hyperekplexic-mutant mice. PTX at a concentration preferentially blocked DH-CBD rescue of functional deficiency of homomeric-mutant GlyRs but not their heteromeric counterparts. Finally, the observation that DH-CBD increased pre-pulse ratio (PPR) suggests an enhanced probability of glycine release in the spinal cord slice of adult hyperekplexic-mutant mice.
\n
\n
\n
\n
\n
6. Summary
\n
Recent progress as summarized in this chapter has indicated that GlyRs are the target that mediates some of the therapeutic effects of nonpsychoactive cannabinoids in the brain. The widespread medical use of cannabis has been so controversial because the plant can produce both therapeutic and unwanted effects. The cannabinoid-GlyRs interaction opens up a new avenue to separate cannabis-induced analgesic effects from cannabis-induced psychoactive effects [89]. For instance, a very recent study has successfully developed a strategy to discover and develop analgesic drugs based on NMR structure of the GlyR and the critical role of residue S296 in THC potentiation of GlyRs [60]. The therapeutic potential for nonpsychoactive cannabinoids by targeting GlyRs has been implied to hyperekplexia disease. Unlike GABAA-acting agents that are plagued by various side effects [90], DH-CBD does not produce significant psychoactive or sedative effects even at high concentrations [58]. Finally, presynaptic GlyRs are proposed to be an emerging target for the pathological mechanism of hyperekplexia disease. This idea is consistent with recent research trend toward the roles of presynaptic and extrasynaptic GlyRs in various neurological disorders [25, 63, 66, 69, 91, 92]. Thus, like postsynaptic GlyRs, presynaptic and extrasynaptic GlyRs should emerge as therapeutic targets for nonpsychoactive cannabinoids in the treatment of various neurological diseases with GlyR deficiency.
\n
\n\n',keywords:"glycine, receptor, cannabinoid, pain, nonpsychoactive, therapeutics, action of mechanism",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/50856.pdf",chapterXML:"https://mts.intechopen.com/source/xml/50856.xml",downloadPdfUrl:"/chapter/pdf-download/50856",previewPdfUrl:"/chapter/pdf-preview/50856",totalDownloads:1256,totalViews:259,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:1,dateSubmitted:"October 13th 2015",dateReviewed:"March 29th 2016",datePrePublished:null,datePublished:"June 15th 2016",dateFinished:null,readingETA:"0",abstract:"The glycine receptors (GlyRs) have been identified as major inhibitory neurotransmission receptors in the brain since the mid of last century. Unfortunately, no therapeutic agent has been developed from targeting these receptors. Accumulating evidence has suggested that GlyRs are one primary target for exogenous and endogenous cannabinoids in the central nervous system. Cannabinoids enhance the function of GlyRs in various neurons in the brain. However, this line of research has been largely ignored since little is known about the molecular mechanism and behavioral implication of cannabinoid modulation of GlyRs. Recent studies using various experimental approaches have explored molecular insights into cannabinoid-GlyR interaction and shed light on the molecular basis of nonpsychoactive cannabinoid modulation of GlyRs. Emerging evidence has suggested that cannabinoid modulation of GlyRs can contribute to some of the cannabis-induced therapeutic effects. In this chapter, I discuss recent development in studies of mechanism and therapeutic potential of cannabinoid modulation of GlyR subunits. This research direction shows considerable promise toward the development of novel therapeutic agents acting at defined modulatory sites of GlyRs in the treatment of various chronic pain, neuromotor disorders, and other GlyR deficiency diseases.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/50856",risUrl:"/chapter/ris/50856",book:{slug:"cannabinoids-in-health-and-disease"},signatures:"Li Zhang",authors:[{id:"179194",title:"Dr.",name:"Li",middleName:null,surname:"Zhang",fullName:"Li Zhang",slug:"li-zhang",email:"lzhang@mail.nih.gov",position:null,institution:{name:"National Institutes of Health",institutionURL:null,country:{name:"United States of America"}}}],sections:[{id:"sec_1",title:"Abbreviations",level:"1"},{id:"sec_2",title:"1. Molecular composition and tissue distribution",level:"1"},{id:"sec_3",title:"2. Presynaptic and extrasynaptic GlyRs",level:"1"},{id:"sec_3_2",title:"2.1. Presynaptic receptors",level:"2"},{id:"sec_4_2",title:"2.2. Extrasynaptic GlyRs",level:"2"},{id:"sec_6",title:"3. GlyR-related disease",level:"1"},{id:"sec_6_2",title:"3.1. GlyRs in chronic pain",level:"2"},{id:"sec_6_3",title:"3.1.1. α3GlyRs in inflammatory pain",level:"3"},{id:"sec_7_3",title:"3.1.2. α3GlyRs in neuropathic pain",level:"3"},{id:"sec_9_2",title:"3.2. Alcohol use disorder",level:"2"},{id:"sec_10_2",title:"3.3. Rare genetic disease: hyperekplexia",level:"2"},{id:"sec_12",title:"4. Cannabinoid interaction with GlyRs",level:"1"},{id:"sec_12_2",title:"4.1. Cannabinoid potentiation of GlyRs",level:"2"},{id:"sec_12_3",title:"4.1.1. Allosteric modulation",level:"3"},{id:"sec_13_3",title:"4.1.2. Subunit-specific modulation",level:"3"},{id:"sec_15_2",title:"4.2. Molecular mechanisms",level:"2"},{id:"sec_15_3",title:"4.2.1. Direct interaction and the site",level:"3"},{id:"sec_16_3",title:"4.2.2. A common molecular basis for endogenous and exogenous cannabinoids",level:"3"},{id:"sec_19",title:"5. Therapeutic potential of glycinergic cannabinoids",level:"1"},{id:"sec_19_2",title:"5.1. Suppression of acute and chronic pain by targeting α3GlyRs",level:"2"},{id:"sec_19_3",title:"5.1.1. α3GlyR dependent",level:"3"},{id:"sec_20_3",title:"5.1.2. A correlation between cannabinoid potentiation of I\nGly and cannabinoid analgesia",level:"3"},{id:"sec_22_2",title:"5.2. Rescue of hyperekplexia by targeting presynaptic α1GlyRs",level:"2"},{id:"sec_22_3",title:"5.2.1. Cannabinoid restoration of exaggerated startle response",level:"3"},{id:"sec_23_3",title:"5.2.2. Therapeutic potential of presynaptic GlyRs",level:"3"},{id:"sec_26",title:"6. Summary",level:"1"}],chapterReferences:[{id:"B1",body:'\nLynch JW. Native glycine receptor subtypes and their physiological roles. Neuropharmacology. 2009 Jan;56(1):303–9. PubMed PMID: 18721822.\n'},{id:"B2",body:'\nDu J, Lu W, Wu S, Cheng Y, Gouaux E. Glycine receptor mechanism elucidated by electron cryo-microscopy. Nature. 2015 Oct 8;526(7572):224–9. PubMed PMID: 26344198. Pubmed Central PMCID: 4659708.\n'},{id:"B3",body:'\nHuang X, Chen H, Michelsen K, Schneider S, Shaffer PL. Crystal structure of human glycine receptor-alpha3 bound to antagonist strychnine. Nature. 2015 Oct 8;526(7572):277–80. PubMed PMID: 26416729.\n'},{id:"B4",body:'\nMeyer G, Kirsch J, Betz H, Langosch D. Identification of a gephyrin binding motif on the glycine receptor beta subunit. Neuron. 1995 Sep;15(3):563–72. PubMed PMID: 7546736.\n'},{id:"B5",body:'\nWeltzien F, Puller C, O’Sullivan GA, Paarmann I, Betz H. Distribution of the glycine receptor beta-subunit in the mouse CNS as revealed by a novel monoclonal antibody. J Comp Neurol. 2012 Dec 1;520(17):3962–81. PubMed PMID: 22592841.\n'},{id:"B6",body:'\nTurecek R, Trussell LO. Reciprocal developmental regulation of presynaptic ionotropic receptors. Proc Natl Acad Sci U S A. 2002 Oct 15;99(21):13884–9. PubMed PMID: 12370408. Pubmed Central PMCID: 129792.\n'},{id:"B7",body:'\nBecker CM, Hoch W, Betz H. Glycine receptor heterogeneity in rat spinal cord during postnatal development. EMBO J. 1988 Dec 1;7(12):3717–26. PubMed PMID: 2850172. Pubmed Central PMCID: 454946. Epub 1988/12/01. eng.\n'},{id:"B8",body:'\nBecker CM, Betz H, Schroder H. Expression of inhibitory glycine receptors in postnatal rat cerebral cortex. Brain Res. 1993 Mar 26;606(2):220–6. PubMed PMID: 8387859.\n'},{id:"B9",body:'\nMalosio ML, Marqueze-Pouey B, Kuhse J, Betz H. Widespread expression of glycine receptor subunit mRNAs in the adult and developing rat brain. EMBO J. 1991 Sep;10(9):2401–9. PubMed PMID: 1651228.\n'},{id:"B10",body:'\nAwatramani GB, Turecek R, Trussell LO. Staggered development of GABAergic and glycinergic transmission in the MNTB. J Neurophysiol. 2005 Feb;93(2):819–28. PubMed PMID: 15456797.\n'},{id:"B11",body:'\nBetz H, Kuhse J, Schmieden V, Laube B, Kirsch J, Harvey RJ. Structure and functions of inhibitory and excitatory glycine receptors. Ann New York Acad Sci. 1999 Apr 30;868:667–76. PubMed PMID: 10414351.\n'},{id:"B12",body:'\nJonsson S, Kerekes N, Hyytia P, Ericson M, Soderpalm B. Glycine receptor expression in the forebrain of male AA/ANA rats. Brain Res. 2009 Dec 11;1305 Suppl:S27–36. PubMed PMID: 19781529. Epub 2009/09/29. eng.\n'},{id:"B13",body:'\nDanglot L, Rostaing P, Triller A, Bessis A. Morphologically identified glycinergic synapses in the hippocampus. Mol Cell Neurosci. 2004 Dec;27(4):394–403. PubMed PMID: 15555918.\n'},{id:"B14",body:'\nAroeira RI, Ribeiro JA, Sebastiao AM, Valente CA. Age-related changes of glycine receptor at the rat hippocampus: from the embryo to the adult. J Neurochem. 2011 Aug;118(3):339–53. PubMed PMID: 21272003.\n'},{id:"B15",body:'\nAvila A, Vidal PM, Dear TN, Harvey RJ, Rigo JM, Nguyen L. Glycine receptor alpha2 subunit activation promotes cortical interneuron migration. Cell Reports. 2013 Aug 29;4(4):738–50. PubMed PMID: 23954789. Pubmed Central PMCID: 3763372.\n'},{id:"B16",body:'\nHarvey RJ, Depner UB, Wassle H, Ahmadi S, Heindl C, Reinold H, et al. GlyR alpha3: an essential target for spinal PGE2-mediated inflammatory pain sensitization. Science. 2004 May 7;304(5672):884–7. PubMed PMID: 15131310.\n'},{id:"B17",body:'\nBaer K, Waldvogel HJ, Faull RL, Rees MI. Localization of glycine receptors in the human forebrain, brainstem, and cervical spinal cord: an immunohistochemical review. Front Mol Neurosci. 2009;2:25. PubMed PMID: 19915682. Pubmed Central PMCID: 2776491.\n'},{id:"B18",body:'\nBode A, Lynch JW. The impact of human hyperekplexia mutations on glycine receptor structure and function. Mol Brain. 2014;7:2. PubMed PMID: 24405574. Pubmed Central PMCID: 3895786.\n'},{id:"B19",body:'\nTurecek R, Trussell LO. Presynaptic glycine receptors enhance transmitter release at a mammalian central synapse. Nature. 2001 May 31;411(6837):587–90. PubMed PMID: 11385573.\n'},{id:"B20",body:'\nYe JH, Wang F, Krnjevic K, Wang W, Xiong ZG, Zhang J. Presynaptic glycine receptors on GABAergic terminals facilitate discharge of dopaminergic neurons in ventral tegmental area. J Neurosci. 2004 Oct 13;24(41):8961–74. PubMed PMID: 15483115.\n'},{id:"B21",body:'\nWang F, Xiao C, Ye JH. Taurine activates excitatory non-synaptic glycine receptors on dopamine neurones in ventral tegmental area of young rats. J Physiol. 2005 Jun 1;565(Pt 2):503–16. PubMed PMID: 15817633. Pubmed Central PMCID: 1464534.\n'},{id:"B22",body:'\nLee EA, Cho JH, Choi IS, Nakamura M, Park HM, Lee JJ, et al. Presynaptic glycine receptors facilitate spontaneous glutamate release onto hilar neurons in the rat hippocampus. J Neurochem. 2009 Apr;109(1):275–86. PubMed PMID: 19200346.\n'},{id:"B23",body:'\nHruskova B, Trojanova J, Kulik A, Kralikova M, Pysanenko K, Bures Z, et al. Differential distribution of glycine receptor subtypes at the rat calyx of held synapse. J Neurosci. 2012 Nov 21;32(47):17012–24. PubMed PMID: 23175852. Pubmed Central PMCID: 3531607.\n'},{id:"B24",body:'\nChoi KH, Nakamura M, Jang IS. Presynaptic glycine receptors increase GABAergic neurotransmission in rat periaqueductal gray neurons. Neural Plast. 2013;2013:954302. PubMed PMID: 24078885. Pubmed Central PMCID: 3773970.\n'},{id:"B25",body:'\nKono Y, Hulsmann S. Presynaptic facilitation of glycinergic mIPSC is reduced in mice lacking alpha3 glycine receptor subunits. Neuroscience. 2016 Feb 3;320:1–7. PubMed PMID: 26851771.\n'},{id:"B26",body:'\nXiong W, Chen SR, He L, Cheng K, Zhao YL, Chen H, et al. Presynaptic glycine receptors as a potential therapeutic target for hyperekplexia disease. Nat Neurosci. 2014 Feb;17(2):232–9. PubMed PMID: 24390226. Pubmed Central PMCID: 4019963.\n'},{id:"B27",body:'\nJeong H-J, Jang I-S, Moorhouse AJ, Akaike N. Activation of presynaptic glycine receptors facilitates glycine release from presynaptic terminals synapsing onto rat spinal sacral dorsal commissural nucleus neurons. J Physiol. 2003 July 15;550(2):373–83.\n'},{id:"B28",body:'\nYe J-H, Wang F, Krnjevic K, Wang W, Xiong Z-G, Zhang J. Presynaptic glycine receptors on GABAergic terminals facilitate discharge of dopaminergic neurons in ventral tegmental area. J Neurosci.. 2004 October 13, 2004;24(41):8961–74.\n'},{id:"B29",body:'\nGriffon N, Buttner C, Nicke A, Kuhse J, Schmalzing G, Betz H. Molecular determinants of glycine receptor subunit assembly. EMBO J. 1999 Sep 1;18(17):4711–21. PubMed PMID: 10469650. Pubmed Central PMCID: 1171544.\n'},{id:"B30",body:'\nPribilla I, Takagi T, Langosch D, Bormann J, Betz H. The atypical M2 segment of the beta subunit confers picrotoxinin resistance to inhibitory glycine receptor channels. EMBO J. 1992 Dec;11(12):4305–11. PubMed PMID: 1385113. Pubmed Central PMCID: 557003. Epub 1992/12/01. eng.\n'},{id:"B31",body:'\nYang Z, Cromer BA, Harvey RJ, Parker MW, Lynch JW. A proposed structural basis for picrotoxinin and picrotin binding in the glycine receptor pore. J Neurochem. 2007 Oct;103(2):580–9. PubMed PMID: 17714449.\n'},{id:"B32",body:'\nTurecek R, Trussell LO. Presynaptic glycine receptors enhance transmitter release at a mammalian central synapse. Nature. 2001;411(6837):587.\n'},{id:"B33",body:'\nDeleuze C, Runquist M, Orcel H, Rabie A, Dayanithi G, Alonso G, et al. Structural difference between heteromeric somatic and homomeric axonal glycine receptors in the hypothalamo-neurohypophysial system. Neuroscience. 2005;135(2):475–83. PubMed PMID: 16125853. Epub 2005/08/30. eng.\n'},{id:"B34",body:'\nGuan YZ, Ye JH. Glycine blocks long-term potentiation of GABAergic synapses in the ventral tegmental area. Neuroscience. 2016 Mar 24;318:134–42. PubMed PMID: 26806277. Pubmed Central PMCID: 4753108.\n'},{id:"B35",body:'\nChiu YC, Liao WT, Liu CK, Wu CH, Lin CR. Reduction of spinal glycine receptor-mediated miniature inhibitory postsynaptic currents in streptozotocin-induced diabetic neuropathic pain. Neurosci Lett. 2016 Jan 12;611:88–93. PubMed PMID: 26598022.\n'},{id:"B36",body:'\nChattipakorn SC, McMahon LL. Pharmacological characterization of glycine-gated chloride currents recorded in rat hippocampal slices. J Neurophysiol. 2002 Mar;87(3):1515–25. PubMed PMID: 11877523.\n'},{id:"B37",body:'\nDeleuze C, Alonso G, Lefevre IA, Duvoid-Guillou A, Hussy N. Extrasynaptic localization of glycine receptors in the rat supraoptic nucleus: further evidence for their involvement in glia-to-neuron communication. Neuroscience. 2005;133(1):175–83. PubMed PMID: 15893641.\n'},{id:"B38",body:'\nKarnani MM, Venner A, Jensen LT, Fugger L, Burdakov D. Direct and indirect control of orexin/hypocretin neurons by glycine receptors. J Physiol. 2011 Feb 1;589(Pt 3):639–51. PubMed PMID: 21135047. Pubmed Central PMCID: 3055548.\n'},{id:"B39",body:'\nSalling MC, Harrison NL. Strychnine-sensitive glycine receptors on pyramidal neurons in layers II/III of the mouse prefrontal cortex are tonically activated. J Neurophysiol. 2014 Sep 1;112(5):1169–78. PubMed PMID: 24872538. Pubmed Central PMCID: 4122733.\n'},{id:"B40",body:'\nFlint AC, Liu X, Kriegstein AR. Nonsynaptic glycine receptor activation during early neocortical development. Neuron. 1998 Jan;20(1):43–53. PubMed PMID: 9459441.\n'},{id:"B41",body:'\nMangin JM, Baloul M, Prado De Carvalho L, Rogister B, Rigo JM, Legendre P. Kinetic properties of the alpha2 homo-oligomeric glycine receptor impairs a proper synaptic functioning. J Physiol. 2003 Dec 1;553(Pt 2):369–86. PubMed PMID: 12972628. Pubmed Central PMCID: 2343566.\n'},{id:"B42",body:'\nSipila ST, Spoljaric A, Virtanen MA, Hiironniemi I, Kaila K. Glycine transporter-1 controls nonsynaptic inhibitory actions of glycine receptors in the neonatal rat hippocampus. J Neurosci. 2014 Jul 23;34(30):10003–9. PubMed PMID: 25057202.\n'},{id:"B43",body:'\nAlmarghini K, Remy A, Tappaz M. Immunocytochemistry of the taurine biosynthesis enzyme, cysteine sulfinate decarboxylase, in the cerebellum: evidence for a glial localization. Neuroscience. 1991;43(1):111–9. PubMed PMID: 1922763.\n'},{id:"B44",body:'\nHussy N, Bres V, Rochette M, Duvoid A, Alonso G, Dayanithi G, et al. Osmoregulation of vasopressin secretion via activation of neurohypophysial nerve terminals glycine receptors by glial taurine. J Neurosci. 2001 Sep 15;21(18):7110–6. PubMed PMID: 11549721.\n'},{id:"B45",body:'\nChoe KY, Olson JE, Bourque CW. Taurine release by astrocytes modulates osmosensitive glycine receptor tone and excitability in the adult supraoptic nucleus. J Neurosci. 2012 Sep 5;32(36):12518–27. PubMed PMID: 22956842.\n'},{id:"B46",body:'\nDeleuze C, Duvoid A, Hussy N. Properties and glial origin of osmotic-dependent release of taurine from the rat supraoptic nucleus. J Physiol. 1998 Mar 1;507 (Pt 2):463–71. PubMed PMID: 9518705. Pubmed Central PMCID: 2230788.\n'},{id:"B47",body:'\nDahchour A, Quertemont E, De Witte P. Taurine increases in the nucleus accumbens microdialysate after acute ethanol administration to naive and chronically alcoholised rats. Brain Res. 1996 Sep 30;735(1):9–19. PubMed PMID: 8905164.\n'},{id:"B48",body:'\nAdermark L, Clarke RB, Olsson T, Hansson E, Soderpalm B, Ericson M. Implications for glycine receptors and astrocytes in ethanol-induced elevation of dopamine levels in the nucleus accumbens. Addict Biol. 2011 Jan;16(1):43–54. PubMed PMID: 20331561.\n'},{id:"B49",body:'\nEricson M, Chau P, Adermark L, Soderpalm B. Rising taurine and ethanol concentrations in nucleus accumbens interact to produce the dopamine-activating effects of alcohol. Adv Exp Med. Biol. 2013;775:215–23. PubMed PMID: 23392937.\n'},{id:"B50",body:'\nBadanich KA, Mulholland PJ, Beckley JT, Trantham-Davidson H, Woodward JJ. Ethanol reduces neuronal excitability of lateral orbitofrontal cortex neurons via a glycine receptor dependent mechanism. Neuropsychopharmacology. 2013 Jun;38(7):1176–88. PubMed PMID: 23314219. Pubmed Central PMCID: 3656360.\n'},{id:"B51",body:'\nJonsson S, Adermark L, Ericson M, Soderpalm B. The involvement of accumbal glycine receptors in the dopamine-elevating effects of addictive drugs. Neuropharmacology. 2014 Jul;82:69–75. PubMed PMID: 24686030.\n'},{id:"B52",body:'\nXiong W, Cui T, Cheng K, Yang F, Chen SR, Willenbring D, et al. Cannabinoids suppress inflammatory and neuropathic pain by targeting alpha3 glycine receptors. J Exp Med. 2012 Jun 4;209(6):1121–34. PubMed PMID: 22585736. Pubmed Central PMCID: 3371734.\n'},{id:"B53",body:'\nHarvey VL, Caley A, Muller UC, Harvey RJ, Dickenson AH. A selective role for alpha3 subunit glycine receptors in inflammatory pain. Front Mol Neurosci. 2009;2:14. PubMed PMID: 19915732. Pubmed Central PMCID: 2776487. Epub 2009/11/17. eng.\n'},{id:"B54",body:'\nBreitinger U, Breitinger HG. Augmentation of glycine receptor alpha3 currents suggests a mechanism for glucose-mediated analgesia. Neurosci Lett. 2016 Jan 26;612:110–5. PubMed PMID: 26656729.\n'},{id:"B55",body:'\nMotoyama N, Morita K, Kitayama T, Shiraishi S, Uezono Y, Nishimura F, et al. Pain-releasing action of platelet-activating factor (PAF) antagonists in neuropathic pain animal models and the mechanisms of action. Eur J Pain. 2013 Sep;17(8):1156–67. PubMed PMID: 23355413.\n'},{id:"B56",body:'\nKallenborn-Gerhardt W, Lu R, Lorenz J, Gao W, Weiland J, Del Turco D, et al. Prolonged zymosan-induced inflammatory pain hypersensitivity in mice lacking glycine receptor alpha2. Behav Brain Res. 2012 Jan 1;226(1):106–11. PubMed PMID: 21924294.\n'},{id:"B57",body:'\nBecker L, von Wegerer J, Schenkel J, Zeilhofer HU, Swandulla D, Weiher H. Disease-specific human glycine receptor alpha1 subunit causes hyperekplexia phenotype and impaired glycine- and GABA(A)-receptor transmission in transgenic mice. J Neurosci. 2002 Apr 1;22(7):2505–12. PubMed PMID: 11923415.\n'},{id:"B58",body:'\nXiong W, Cheng K, Cui T, Godlewski G, Rice KC, Xu Y, et al. Cannabinoid potentiation of glycine receptors contributes to cannabis-induced analgesia. Nat Chem Biol. 2011 May;7(5):296–303. PubMed PMID: 21460829. Pubmed Central PMCID: 3388539.\n'},{id:"B59",body:'\nZhang JY, Gong N, Huang JL, Guo LC, Wang YX. Gelsemine, a principal alkaloid from Gelsemium sempervirens Ait., exhibits potent and specific antinociception in chronic pain by acting at spinal alpha3 glycine receptors. Pain. 2013 Nov;154(11):2452–62. PubMed PMID: 23886522.\n'},{id:"B60",body:'\nWells MM, Tillman TS, Mowrey DD, Sun T, Xu Y, Tang P. Ensemble-based virtual screening for cannabinoid-like potentiators of the human glycine receptor alpha1 for the treatment of pain. J Med Chem. 2015 Apr 9;58(7):2958–66. PubMed PMID: 25790278. Pubmed Central PMCID: 4414066.\n'},{id:"B61",body:'\nMolander A, Soderpalm B. Accumbal strychnine-sensitive glycine receptors: an access point for ethanol to the brain reward system. Alcohol Clin Exp Res. 2005 Jan;29(1):27–37. PubMed PMID: 15654288.\n'},{id:"B62",body:'\nMolander A, Soderpalm B. Glycine receptors regulate dopamine release in the rat nucleus accumbens. Alcohol Clin Exp Res. 2005 Jan;29(1):17–26. PubMed PMID: 15654287.\n'},{id:"B63",body:'\nChau P, Hoifodt-Lido H, Lof E, Soderpalm B, Ericson M. Glycine receptors in the nucleus accumbens involved in the ethanol intake-reducing effect of acamprosate. Alcohol Clin Exp Res. 2009 Jan;34(1):39–45. PubMed PMID: 19860809. Epub 2009/10/29. eng.\n'},{id:"B64",body:'\nAdermark L, Clarke RB, Olsson T, Hansson E, Soderpalm B, Ericson M. Implications for glycine receptors and astrocytes in ethanol-induced elevation of dopamine levels in the nucleus accumbens. Addict Biol. 2010 Jan;16(1):43–54. PubMed PMID: 20331561. Epub 2010/03/25. eng.\n'},{id:"B65",body:'\nLi J, Nie H, Bian W, Dave V, Janak PH, Ye JH. Microinjection of glycine into the ventral tegmental area selectively decreases ethanol consumption. J Pharmacol Exp Ther. Epub 2012 Jan 11. Apr;341(1):196–204. doi: 10.1124/jpet.111.190058.\n\n'},{id:"B66",body:'\nAdermark L, Clarke RB, Soderpalm B, Ericson M. Ethanol-induced modulation of synaptic output from the dorsolateral striatum in rat is regulated by cholinergic interneurons. Neurochem Int. 2011 May;58(6):693–9. PubMed PMID: 21333709.\n'},{id:"B67",body:'\nClarke RB, Adermark L, Chau P, Soderpalm B, Ericson M. Increase in nucleus accumbens dopamine levels following local ethanol administration is not mediated by acetaldehyde. Alcohol Alcohol. 2014 Sep–Oct;49(5):498–504. PubMed PMID: 25063803.\n'},{id:"B68",body:'\nClarke RB, Soderpalm B, Lotfi A, Ericson M, Adermark L. Involvement of inhibitory receptors in modulating dopamine signaling and synaptic activity following acute ethanol exposure in striatal subregions. Alcohol Clin Exp Res. 2015 Dec;39(12):2364–74. PubMed PMID: 26614538.\n'},{id:"B69",body:'\nLi J, Nie H, Bian W, Dave V, Janak PH, Ye JH. Microinjection of glycine into the ventral tegmental area selectively decreases ethanol consumption. J Pharmacol Exp Ther. 2012 Apr;341(1):196–204. PubMed PMID: 22238211. Pubmed Central PMCID: 3310696.\n'},{id:"B70",body:'\nBlednov YA, Benavidez JM, Black M, Leiter CR, Osterndorff-Kahanek E, Harris RA. Glycine receptors containing alpha2 or alpha3 subunits regulate specific ethanol-mediated behaviors. J Pharmacol Exp Ther. 2015 Apr;353(1):181–91. PubMed PMID: 25678534. Pubmed Central PMCID: 4366753.\n'},{id:"B71",body:'\nBlednov YA, Benavidez JM, Homanics GE, Harris RA. Behavioral characterization of knockin mice with mutations M287L and Q266I in the glycine receptor alpha1 subunit. J PharmacolExp Ther. 2012 Feb;340(2):317–29. PubMed PMID: 22037202. Pubmed Central PMCID: 3263963.\n'},{id:"B72",body:'\nAguayo LG, Castro P, Mariqueo T, Munoz B, Xiong W, Zhang L, et al. Altered sedative effects of ethanol in mice with alpha1 glycine receptor subunits that are insensitive to Gbetagamma modulation. Neuropsychopharmacology. 2014 Oct;39(11):2538–48. PubMed PMID: 24801766. Pubmed Central PMCID: 4207329.\n'},{id:"B73",body:'\nDavies JS, Chung SK, Thomas RH, Robinson A, Hammond CL, Mullins JG, et al. The glycinergic system in human startle disease: a genetic screening approach. Front Mol Neurosci. 2010;3:8. PubMed PMID: 20407582. Pubmed Central PMCID: 2854534.\n'},{id:"B74",body:'\nShiang R, Ryan SG, Zhu YZ, Hahn AF, O’Connell P, Wasmuth JJ. Mutations in the alpha 1 subunit of the inhibitory glycine receptor cause the dominant neurologic disorder, hyperekplexia. Nat Genet. 1993 Dec;5(4):351–8. PubMed PMID: 8298642.\n'},{id:"B75",body:'\nHarvey RJ, Topf M, Harvey K, Rees MI. The genetics of hyperekplexia: more than startle! Trends Genet. 2008 Sep;24(9):439–47. PubMed PMID: 18707791. Epub 2008/08/19. eng.\n'},{id:"B76",body:'\nJames VM, Bode A, Chung SK, Gill JL, Nielsen M, Cowan FM, et al. Novel missense mutations in the glycine receptor beta subunit gene (GLRB) in startle disease. Neurobiol Dis. 2013 Apr;52:137–49. PubMed PMID: 23238346. Pubmed Central PMCID: 3581774.\n'},{id:"B77",body:'\nHejazi N, Zhou C, Oz M, Sun H, Ye JH, Zhang L. {Delta}9-tetrahydrocannabinol and endogenous cannabinoid anandamide directly potentiate the function of glycine receptors. Mol Pharmacol. 2006 Mar;69(3):991–7. PubMed PMID: 16332990.\n'},{id:"B78",body:'\nYang Z, Aubrey KR, Alroy I, Harvey RJ, Vandenberg RJ, Lynch JW. Subunit-specific modulation of glycine receptors by cannabinoids and N-arachidonyl-glycine. Biochem Pharmacol. 2008 Oct 15;76(8):1014–23. PubMed PMID: 18755158. Epub 2008/08/30. eng.\n'},{id:"B79",body:'\nAhrens J, Demir R, Leuwer M, de la Roche J, Krampfl K, Foadi N, et al. The nonpsychotropic cannabinoid cannabidiol modulates and directly activates alpha-1 and alpha-1-Beta glycine receptor function. Pharmacology. 2009;83(4):217–22. PubMed PMID: 19204413.\n'},{id:"B80",body:'\nDelaney AJ, Esmaeili A, Sedlak PL, Lynch JW, Sah P. Differential expression of glycine receptor subunits in the rat basolateral and central amygdala. Neurosci Lett. 2009 Jan 22;469(2):237–42. PubMed PMID: 19995593. Epub 2009/12/10. eng.\n'},{id:"B81",body:'\nYevenes GE, Zeilhofer HU. Molecular sites for the positive allosteric modulation of glycine receptors by endocannabinoids. PloS One. 2011;6(8):e23886. PubMed PMID: 21901142. Pubmed Central PMCID: 3162021.\n'},{id:"B82",body:'\nXiong W1, Wu X, Li F, Cheng K, Rice KC, Lovinger DM, Zhang L. A common molecular basis for exogenous and endogenous cannabinoid potentiation of glycine receptors. J Neurosci. 2012; Sep 12;32(37):12979.\n'},{id:"B83",body:'\nHejazi N, Zhou C, Oz M, Sun H, Ye JH, Zhang L. Delta9-tetrahydrocannabinol and endogenous cannabinoid anandamide directly potentiate the function of glycine receptors. Mol Pharmacol. 2006 Mar;69(3):991–7. PubMed PMID: 16332990.\n'},{id:"B84",body:'\nHuestis MA, Cone EJ. Relationship of Delta 9-tetrahydrocannabinol concentrations in oral fluid and plasma after controlled administration of smoked cannabis. J Anal Toxicol. 2004 Sep;28(6):394–9. PubMed PMID: 15516285.\n'},{id:"B85",body:'\nLozovaya N, Yatsenko N, Beketov A, Tsintsadze T, Burnashev N. Glycine receptors in CNS neurons as a target for nonretrograde action of cannabinoids. J Neurosci. 2005 Aug 17;25(33):7499–506. PubMed PMID: 16107637.\n'},{id:"B86",body:'\nXiong W, Wu X, Li F, Cheng K, Rice KC, Lovinger DM, et al. A common molecular basis for exogenous and endogenous cannabinoid potentiation of glycine receptors. J Neurosci. 2012 Apr 11;32(15):5200–8. PubMed PMID: 22496565. Pubmed Central PMCID: 3334839.\n'},{id:"B87",body:'\nZimmer A, Zimmer AM, Hohmann AG, Herkenham M, Bonner TI. Increased mortality, hypoactivity, and hypoalgesia in cannabinoid CB1 receptor knockout mice. Proc Natl Acad Sci U S A. 1999 May 11;96(10):5780–5. PubMed PMID: 10318961. Pubmed Central PMCID: 21937.\n'},{id:"B88",body:'\nBakker MJ, van Dijk JG, van den Maagdenberg AM, Tijssen MA. Startle syndromes. Lancet Neurol. 2006 Jun;5(6):513–24. PubMed PMID: 16713923. Epub 2006/05/23. eng.\n'},{id:"B89",body:'\nChristie MJ, Vaughan CW. Receptors: cannabis medicine without a high. Nat Chem Biol. 2011 May;7(5):249–50. PubMed PMID: 21502945. Epub 2011/04/20. eng.\n'},{id:"B90",body:'\nAshton H. Guidelines for the rational use of benzodiazepines. When and what to use. Drugs. 1994 Jul;48(1):25–40. PubMed PMID: 7525193. Epub 1994/07/01. eng.\n'},{id:"B91",body:'\nYe JH, Tao L, Ren J, Schaefer R, Krnjevic K, Liu PL, et al. Ethanol potentiation of glycine-induced responses in dissociated neurons of rat ventral tegmental area. Journal Pharmacol Exp Ther. 2001 Jan;296(1):77–83. PubMed PMID: 11123365.\n'},{id:"B92",body:'\nSebe JY, Eggers ED, Berger AJ. Differential effects of ethanol on GABA(A) and glycine receptor-mediated synaptic currents in brain stem motoneurons. J Neurophysiol. 2003 Aug;90(2):870–5. PubMed PMID: 12702707.\n'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Li Zhang",address:"lzhang@mail.nih.gov",affiliation:'
Laboratory of Integrative Neuroscience, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, MA, USA
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\n
1. Introduction
\n
The ankle joint is the most commonly affected joint in sports of which lateral ankle sprains are the most common. The sports in which lateral ankle sprains are a frequent occurrence are football, basketball, running, volleyball, tennis, badminton, ballet/dance, etc. In many sports the rate of injury is as high as 70%. Unilateral ankle sprains are reported in 52%, whereas for bilateral ankle sprains, the number is 48%. The recurrence rate of ankle injury in athletes is 73% [1]. The incidence is high between 15 and 19 years of age with no significant difference in the gender [2].
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2. Biomechanics
\n
The lateral ankle compartment comprises the anterior talofibular ligament (ATFL), the calcaneofibular ligament (CFL), and the posterior talofibular ligament (PTFL). The most commonly injured ligament is the ATFL as it is the weakest of all three ligaments. In frequency of injury, the ATFL is followed by the calcaneofibular ligament CFL [3]. The PTFL is rarely injured as it is the strongest of all the three ligaments. The most common mechanism of injury in lateral ankle sprains is when, in forced plantar flexion, inversion occurs with excessive ankle supination. In that position the ankle joint is the most unstable. In the course of the inversion, the body’s center of gravity moves over the ankle leading to ankle sprains [2]. There are three clinical grades of lateral ankle sprains [4, 5, 6].
Grade I—Mild. There is an incomplete tear of ATFL with little swelling and tenderness, minimal or no functional loss, and no mechanical joint instability.
Grade II—Moderate. Complete tear of ATFL with or without an incomplete tear of CFL with moderate pain, swelling, and tenderness over the involved structures; some joint motion is lost, and joint instability is mild to moderate.
Grade III—Severe. Complete tears of ATFL and CFL with marked swelling, hemorrhage, and tenderness. There is loss of function, and joint motion and instability are markedly abnormal.
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3. Chronic ankle instability (CAI)
\n
Athletes with chronic ankle instability give a history of two or three severe ankle sprains with the main complaint being intermittent giving out of the ankle. The athlete often complains of difficulty and apprehension on uneven surfaces. Even mild exacerbations lead to short-term dysfunction. It is characterized by residual ankle instability as a result of either mechanical ankle stability or functional ankle instability or a combination of both [6].
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4. Mechanical and functional instability
\n
Mechanical instability (MI) and functional instability (FI) are both due to recurrent lateral ankle sprains. Mechanical instability is defined as an increase in the accessory movements in the joint leading to hypermobility. Residual MI usually results from a tear or lengthening of one of the ligamentous structures supporting the joint and suggests a suboptimal healing process after injury. A lesser known phenomenon is hypomobility leading to ankle instability. Joint hypomobility can be intra-articular or extra-articular, giving rise to restricted range of motion at the ankle. Hypomobility occurs at the subtalar, talocrural joint, distal tibiofibular joint, and proximal tibiofibular joint [7, 8].
\n
As the joint develops MI, proprioceptive changes occur, which result in alterations in defense mechanism to prevent injuries, thus leading to CAI. FI can result in balance deficits, joint position sense deficits, delayed peroneal muscle reaction time, altered common peroneal nerve function, strength deficits, a decreased range of motion (ROM), sinus tarsi syndrome, and anterolateral impingement syndrome.
\n
\n
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5. Rehabilitation
\n
Early mobilization of ankle sprains as compared with cast immobilization has been shown to be more comfortable as it results in less pain and provides for an earlier return to work. Cast immobilization does not improve healing compared with an active mobilization rehabilitation program and may have negative implications in relation to muscle wasting and stiffness. Functional treatment is considered better in achieving more effective mobilization and an earlier return to daily activities. Lateral ankle sprains respond well to the conservative treatment which includes initially RICE—rest, ice, compression, and elevation—followed by early mobilization. Rehabilitation focuses on restoring ROM, strength, balance, and normal gait patterns. Functional rehabilitation begins on the day of injury and continues until pain-free gait and activities are attained. Functional rehabilitation has four aspects: ROM, strengthening, proprioception, and activity-specific training. Ankle joint stability is a prerequisite to the institution of functional rehabilitation. Since Grade I and Grade II injuries are considered stable, functional rehabilitation should begin immediately.
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5.1 Reduce pain and swelling
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\n
5.1.1 Rest
\n
Rest is prescribed to avoid undue stress on the joint. It is required to reduce the metabolic demands on the injured tissue and thus avoid increased blood flow. It also helps in avoiding stress on the injured tissue that might disrupt the fragile fibrin bond, which is the first element of the repair process. Rest can be applied selectively to allow some general activity, but athletes must avoid stressful activities.
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5.1.2 Ice
\n
Cryotherapy involves a nice bath with a temperature of 4°–10°C for 12–20 min, one to three times per day, and applying an ice pack to the injured area for 15–20 min, one to three times per day. Ice therapy should be started immediately after the injury and ice application initiated within day 0 or day 1. Both have shown better results and return to full activity as compared to when the ice was applied after 48 h. Ice application should provide deep penetration to gain full benefits. Also the ice should not be held immobile in one area or frostbites may occur.
\n
Ice application causes vasoconstriction which decreases blood flow and therefore swelling to the injured area. The lowering of tissue temperature decreases the metabolism and the chemical actions of cells and thus lowers the oxygen and nutrient needs in the affected area. Decreased blood flow limits edema; there is less histamine release and therefore less capillary breakdown than would normally be present after injury. There is better lymphatic drainage from the injured area because of the lower pressure on the extravascular fluid (Table 1).
\n
\n
\n
\n
\n\n
\n
Stage
\n
Duration (min)
\n
Sensation
\n
\n\n\n
\n
Stage 1
\n
1–3
\n
A cold feeling is noted
\n
\n
\n
Stage 2
\n
2–7
\n
Burning or aching
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\n
\n
Stage 3
\n
5–12
\n
Local numbness and anesthesia (decreased conductivity of regional nerve fibers)
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\n
\n
Stage 4
\n
12–15
\n
Reflex deep tissue vasodilation without an increase in metabolism
\n
\n\n
Table 1.
Cryotherapy generates four stages of sensation [9].
\n
Hence, the rationale of minimum 15 min of cryotherapy per treatment.
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\n
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5.1.3 Compression and elevation
\n
Compression and elevation work better in combination with cryotherapy. Compression with an adhesive bandage and a foot elevation of more than 45° is the standard prescribed treatment for lateral ankle sprains. Compression can also be achieved by both adhesive and nonadhesive tapes, but it is important to renew them timely as the compression wears off with time. Normally a nonadhesive tape should be renewed after 3 days, and an adhesive tape should be renewed after 5 days [10]. This prevents swelling and immobilizes the injured area which prevents further injury and thus promotes healing. Passive exercises can be started in stage 3 which is the local numbness stage in which the athlete experiences less discomfort when exercising.
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\n
\n
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5.2 Improve range of motion (ROM)
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5.2.1 Range of motion exercises
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Range of motion exercises include both active and passive exercises. Achilles tendon stretching should be started within 48–72 h in a pain-free range irrespective of weight-bearing status of the athlete to avoid the tissue from contracting. Self-passive stretches can also be given with the help of a towel. Next, the stretches should be extended to weight-bearing position, which can be done by standing on an inclined surface and asking the athlete to shift his/her weight forward. The stretches should be maintained 15–30 s, repeated 10 times, and should be done 3–5 times per day. Passive exercises are followed by active ROM exercises whereby the athlete can do alphabet letter exercises, i.e., drawing letters in the air both in upper and lower cases. The exercises should be done 2–3 times per hour, 4–5 times per day. Stationary biking can also be included to improve dorsiflexion and plantar flexion motion in a controlled environment while providing a cardiovascular workout for the athlete.
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\n
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5.2.2 Manual therapy
\n
Manual therapy is started within 48 h after the injury when ankle dorsiflexion is restricted. To improve range, a gentle oscillating passive joint mobilization is given. Here the talus is moved posteriorly. By the convex concave rule, when the talus is moved posteriorly, the convex talus rolls upward and slides posteriorly on the concave surface of the crux, thus improving the dorsiflexion range. In a technique described by Maitland [11], with the athlete in supine position, the affected foot is taken in the available pain-free ROM in dorsiflexion. Gentle oscillations are then given to the joint to avoid pain and spasm. The oscillations are given for 60 s, 2 or more times with a rest of 10 s taken in between.
\n
Mobilization with movement is another technique of manual therapy suggested by Mulligan [12] which helps with increasing the ROM actively. In this technique the athlete position is high kneeling with weight-bearing on the affected limb or standing with the affected foot placed forward. In both positions the ankle is in neutral position. A padded belt is used for mobilization and is placed in such a way that the bottom of the belt is leveled with the inferior margin of the medial malleolus. The position of the mobilization belt allows the examiner to fix the talus and calcaneus with his/her hands and draws the tibia forward on the talus, thereby creating a relative posterior talar glide. Once the glide is given, the athlete actively dorsiflexes the ankle in a pain-free range. The glide should be maintained throughout the movement. Two sets of 10 repetitions, separated by a 2-min rest, are performed. Once ROM is achieved and swelling and pain are controlled, the athlete is ready to proceed to the strengthening phase of rehabilitation. Guidelines suggest that a normal ROM should be achieved within 2 weeks after injury [13].
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\n
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5.3 Improve strength
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Strengthening of weakened muscles is essential for a quick recovery and thus helps in preventing re-injury. An eversion to inversion strength ratio >1.0 is an important indicator of ankle sprain injury [14, 15]. Exercises should focus on strengthening the peroneal muscles because insufficient strength in this group of muscles has been associated with CAI and recurrent injury. However, all muscles of the ankle should be targeted, and all exercises should be performed bilaterally. When the training is performed bilaterally, we can expect substantial strength gains in both extremities. Strengthening begins with isometric exercises performed against an immovable object in four directions of ankle movement and is progressed to dynamic resistive exercises (isotonic exercises) using ankle weights, surgical tubing, or resistance bands.
\n
With a structured rehabilitation program, the athlete can create continuous goals and more easily appreciate improvements. A daily adjustable progressive resistance exercise (DAPRE) strength progression, originally described by Knight [16] and later modified by Perrin and Gieck [17], can be used to create a structured progression of exercises for the athletes. The strengthening exercises should be performed with an emphasis on the eccentric component. Athletes should be instructed to pause 1 s between the concentric and eccentric phases of exercise and perform the eccentric component over a 4-s period. Concentric contraction refers to the active shortening of the muscle with resultant lengthening of the resistance band, while eccentric contraction involves the passive lengthening of the muscle by the elastic pull of the band. Resistive exercises should be performed (2–3 sets of 10–12 repetitions) in all four directions twice a day. As weight-bearing strengthening exercises, toe raises, heel walks, and toe walks should be incorporated to regain strength and coordination. Toe curling exercises with paper or towel and marble picking should also be included for strengthening of the foot musculature (Table 2).
The athlete should proceed to the next line when he/she can lock out (complete with correct form) the 4th set 10 times.
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\n
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5.4 Improve proprioception and balance
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Once the athlete achieves full weight-bearing without pain, proprioceptive training is started for the recovery of balance and postural control. Various devices have been designed for this phase of rehabilitation. Their use in performance with a series of progressive drills has effectively returned athletes to a high functional level. As somatosensory and visual feedback is altered, the athlete must develop consistent motor patterns even with inconsistent feedback. Furthermore, the athlete can be tested under various visual and support conditions. The simplest device for proprioceptive training is the wobble board. The athlete is instructed to stand on the wobble board on one foot and shift his or her weight, causing the disc’s edge to scribe a continuous circular path. These exercises can be progressed by having the athlete use different-sized hemispheres and by varying visual input. A common progression when performing balance exercise is to move from a position of non-weight-bearing to weight-bearing, bilateral stance to unilateral stance, eyes open to eyes closed, firm surface to soft surface, uneven or moving surface. Another variant is when the therapist manually moves the ankle and foot through various positions and then asks the athlete to actively and passively replicate the joint angles. This helps improving joint position sense. As the body is trained to sense directions from perturbation, sensory input is received from all parts of the body and sent to the central nervous system via afferent pathways. Therefore, conscious and unconscious appreciation is important to protect functional joint stability. Proprioception is useful for preventing injury in slow, moderately quick, or even quick tasks; however, it may not be adequate for forces that challenge the neuromuscular system at the highest levels. The therapist should also focus on variability of speed and intensity while training proprioception and balance (Table 3).
\n
\n
\n
\n
\n
\n\n
\n
No material
\n
Ball
\n
Balance board
\n
Ball + balance board
\n
\n\n\n
\n
Exercise 1 One-legged stance with the knee flexed. Step out on the other leg with the knee flexed, and keep balance for 5 s. Repeat 10 times for both legs Variations 1 2 3 4
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Exercise 3 *Make pairs. Both stand in one-legged stance with the knee flexed. Keep a distance of 5 m. Throw and/or catch a ball 5 times while maintaining balance. Repeat 10 times for both legs Variations 1 2
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Exercise 5 One legged stance on the balance board with the knee flexed. Maintain balance for 30 s and change stance leg. Repeat twice for both legs Variations 1 2 3 4
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Exercise 10 Athlete stands with both feet on the balance board. Throw and/or catch a ball 10 times with one hand while maintaining balance. Repeat twice
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\n
\n
Exercise 2 One-legged stance with the hip and the knee flexed. Step out on the other leg with the hip and knee flexed, and keep balance for 5 s. Repeat 10 times for both legs Variations 1 2 3 4
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Exercise 4 *Make pairs. Stand both in one-legged stance with the hip and knee flexed. Keep a distance of 5 m. Throw and/or catch a ball 5 times while maintaining balance. Repeat 10 times for both legs Variations 1 2
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Exercise 6 One-legged stance on the balance board with the hip and knee flexed. Maintain balance for 30 s and change stance leg. Repeat twice for both legs Variations 1 2 3 4
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Exercise 11 Athlete stands in one-legged stance with the knee flexed on the balance board. Throw and/or catch a ball 10 times with one hand while maintaining balance. Repeat twice for both legs Variations 1 2
\n
\n
\n
Variations on basic exercises: The standing leg is stretched The standing leg is flexed The standing is stretched and first eyes are opened, followed by eyes closed The standing leg is flexed and first eyes are open followed by eyes closed The standing leg is stretched and upper hand technique (throwing the ball from above the head) The standing leg is flexed and upper hand technique The standing leg is stretched and lower hand technique (throwing the ball while keeping the hand below the waist) The standing leg is flexed and lower hand technique *This can be done by the therapist, and the athlete or the athlete can stand opposite to the wall at a distance of 5 m
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Exercise 7 Step slowly over the balance board with one foot on the balance board. Maintain the balance board in a horizontal position while stepping over. Repeat 10 times for both legs
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Exercise 12 Athlete stands in one-legged stance with the hip and knee flexed on the balance board; the other has the same position on the floor. Throw and/or catch a ball 10 times with one hand while maintaining balance. Repeat twice for both legs Variations 1 2
\n
\n
\n
Exercise 8 Stand with both feet on the balance board. Make 10 knee flexions while maintaining balance
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Exercise 13 Athlete stands with both feet on the balance board. Throw the ball with an upper hand technique 10 times while maintaining balance. Repeat twice for both legs Variations 5 6 7 8
\n
\n
\n
Exercise 9 One-legged stance on the balance board with the knee flexed. Make 10 knee flexions while maintaining balance. Repeat twice for both legs
\n
Exercise 14 Athlete stands in one-legged stance with the knee flexed on the balance board. Throw the ball with an upper hand technique 10 times while maintaining balance. Repeat twice for both legs Variations 5 6 7 8
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\n\n
Table 3.
Proprioceptive exercises (the variation and changes should be according to the athlete’s requirements).
Adapted from: The Effect of a Proprioceptive Balance Board Training Program for the Prevention of Ankle Sprains: A Prospective Controlled Trial [18].
\n*All the exercises done by the Athlete, can be done in pairs or the athlete can stand opposite to a wall at distance of 5 m
\n
\n
\n
5.5 Sports-specific training
\n
Once the distance walked by the athlete is no longer limited by pain, he/she can be put on sports-specific training or advanced training. The use of sports-specific means of training, parallel to general conditioning training, leads to considerable improvement of performance among athletes. The sports-specific training includes intricate activities like jogging which eventually progresses to running, backward running, and pattern running. Circles and figure of 8 are commonly employed patterns. These activities can also be done using ankle weight to increase the difficulty level. Star excursion balance training can also be used in which the athlete stands on the sprained ankle while using another foot to reach as far as possible in eight directions as outlined in the Star Excursion Balance Test. The exercise can consist of 8–10 rounds clockwise and counterclockwise foot reach with 3 s rest between each direction. The difficulty level can be increased by adding variations to the exercise such as with the sprained ankle (affected leg’s knee) flexed, eyes opened, followed by eyes closed. At higher speed, i.e., at an angular velocity of 120°/s, the eversion to inversion ratio is >1.0, adding to the risk of injuries [19]. Hence, resistance bands can be used to strengthen the ankle musculature, i.e., training an athlete on an isokinetic machine while tying the band on the affected ankle and with the therapist holding the other end and maintaining the resistance through the movement. This should be done for 15–20 repetitions 1–2 times/day and with increasing progression. Specific training can include functional activities on various surfaces, e.g., trampoline and foam, and in water with weights. Repetitions should be 5–20, 1–2 times/day (Figure 1).
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Figure 1.
Star excursion balance test [20]. Note: Star Excursion Balance Test for left-leg dominant participants (Posterior direction is behind athlete’s right leg). Abbreviations: A, anterior; AM, anterior-medial; M, medial; PM, posterior-medial; P, posterior; PL, posterior-lateral; L, lateral; AL, anterior-lateral.
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\n
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5.6 Criteria for return to sports
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The athlete can participate fully in the sporting activity once the pain has been reduced completely. The progression should be gradual in order to stress the ligaments without causing further harm. Full participation should be allowed once the athlete has complete range of motion, 80–90% of preinjury strength and a normal gait pattern including the ability to perform sports-specific activities such as cutting and landing without any compensation due to the injury. The athlete should be able to complete a full practice without pain or swelling.
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\n
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5.7 Taping and bracing
\n
Taping and bracing the ankle can be used for prevention as well as for rehabilitation. Application of tapes and braces is helpful in the prevention of lateral ankle sprains and in the recurrence of injuries. Application of a tape or a brace increases the afferent feedback from cutaneous receptors, which lead to improved ankle joint position sense. This increased stimulation results in a more appropriate positioning of the unstable ankle and protects it from re-injury. Hence it helps improve joint position sense through proprioceptive mechanism.
Taping: The major role of taping is to prevent extreme range of movements and to reduce abnormal patterns of movements of the ankle. Various techniques are in use, but the most common techniques are basket weave with stirrup and heel lock and basket weave and heel lock techniques. Taping has mechanical effects: it decreases movement of inversion and plantar flexion and increases the force required for a specific displacement in inversion and plantar flexion. Taping helps in decreasing the extent of non-weight-bearing talar tilt. It also limits the full weight-bearing talar tilt. Athletes with the greatest instability benefit most from the tape. Although taping does improve mechanical instability, the restricting effect is lost after varying periods of exercise. About 40% of taping effect is lost after 10 min of vigorous exercise like jumping, pivoting, running, etc.
Kinesio™ taping: Unlike structurally supportive tape, such as white athletic tape, Kinesio™ tape is therapeutic in nature. It differs from the traditional athletic tape with respect to its elasticity, i.e., it can be stretched up to 140% of its original length before applying it on the skin. It provides a constant pulling (shear) force to the skin unlike traditional white athletic tape. The fabric of this tape is air permeable and water resistant and can be worn for repetitive days. The proposed mechanisms in which the Kinesio™ tape works are:
It corrects muscle function by strengthening weakened muscles.
It improves circulation of blood and lymph by eliminating tissue fluid or bleeding beneath the skin by moving the muscle.
It reduces pain through neurological suppression.
It repositions subluxated joints by relieving abnormal muscle tension, helping to return the function of fascia and muscles [21].
It improves proprioception through increased stimulation to cutaneous mechanoreceptors [22].
Bracing: Ankle bracing can make a significant contribution to preventing lateral ankle sprains. It also shows a significant reduction in the frequency of ankle sprain recurrence. Ankle braces have certain advantages over tape allowing self-application without the expertise of qualified personnel. They are convenient to apply and to remove; they are reusable, readjustable, and washable. There are nonrigid and semirigid braces. The nonrigid ones are often made of canvas or a neoprene-type material, which can easily be slipped on and off, and some are with additional lacing. The semirigid braces mostly consist of bimalleolar struts made of thermoplastic materials attached by Velcro straps. Nowadays different braces are used such as lace-up braces and the Swede-O (Swede-O-Universal, North Branch, MN) and multiple models by McDavid Sports Medical Products (Woodridge, IL); lace-up braces with straps such as the ASO (Medical Specialties, Charlotte, NC), the RocketSoc (DonJoy Orthopedics, Inc., Vista, CA), and the Ankle Brace Lock (Breg, Vista, CA); and semirigid plastic braces with strapping configurations such as the Ankle Ligament Protector (DonJoy Orthopedics, Inc.), the Universal Ankle Stirrup (DonJoy Orthopedics, Inc.), the T2 Active Ankle Support (Active Ankle, Louisville, KY) and the Ultra Ankle, and the Guardian Ankle (McDavid Sports Medical Products).
\n\n
Semirigid brace like Swede-O-Universal and nonrigid brace like subtalar supports provide a better non-weight-bearing restriction in plantar flexion, dorsiflexion, and eversion than taping after 15 min of activity. A strong thermoplastic semirigid ankle brace significantly reduces talar and subtalar motions of plantarflexion, inversion, and adduction. In summary, ankle taping and bracing:
Restrict ankle range of motion.
Reduce injury and recurrence rate.
Improve proprioception.
Lose limitation of movement after exercise.
Have no negative effect on most performance tests.
Have little negative effect on other joints.
\n\n
\n
\n
\n
6. Grade III lateral ankle sprains
\n
Grade III lateral ankle sprains occur when there is a complete rupture of both ATFL and CFL. Although the initial line of management remains a functional rehabilitation, surgery should be considered if the symptoms persist. The feeling of giving way, defined as functional instability or true mechanical instability, is frequently experienced. This can be demonstrated by provocative tests such as the anterior drawer or talar tilt (either clinically or by stress radiography). Particular attention should be directed at the diagnosis and correction of subtle subtalar instability in individuals with functional instability. Surgical repairs are aimed at the reconstruction of the normal anatomy by overlapping the existing joint capsule and lateral ligaments. The rehabilitation protocol post-surgery remains the same as that of the conservative treatment.
\n
\n
\n
7. Conclusion
\n
The early rehabilitation of lateral ankle ligament sprains focuses on gaining full recovery by starting it within 24–48 h post injury. Most of the sprains respond well to functional treatment. Rehabilitation programs should be structured and individualized. In the acute phase, the focus should be on controlling inflammation, reestablishing full range of motion and gaining strength. Once the athlete achieves a pain-free range of motion and weight-bearing, balance-training exercises should be included to regulate neuromuscular control. Advanced-phase rehabilitation exercises should focus on regaining normal function. These should include sports-specific exercises specific to the particular sport played by the athlete. While having a basic guideline to follow for the rehabilitation of lateral ankle sprains, it is important to remember that individuals respond differently to exercises. Therefore, each program needs to be modified to fit the individual’s needs.
\n
\n\n',keywords:"lateral ankle sprains, athlete, sports, rehabilitation, exercise",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/70162.pdf",chapterXML:"https://mts.intechopen.com/source/xml/70162.xml",downloadPdfUrl:"/chapter/pdf-download/70162",previewPdfUrl:"/chapter/pdf-preview/70162",totalDownloads:476,totalViews:0,totalCrossrefCites:0,dateSubmitted:"May 14th 2019",dateReviewed:"September 3rd 2019",datePrePublished:"November 22nd 2019",datePublished:"July 29th 2020",dateFinished:null,readingETA:"0",abstract:"Lateral ankle sprains are one of the most common injuries in athletes. The rate of injury is as high as 70%. The most commonly involved ligament is the anterior talofibular ligament (ATFL), followed by the calcaneofibular (CFL) and posterior talofibular ligament (PTFL). The common mechanism of injury is inversion with excessive ankle supination in forced plantarflexion when the ankle joint is in its most unstable position. There are three grades of ankle sprains: Grade I, mild with an incomplete tear of ATFL; Grade II, moderate with a complete tear of ATFL with or without an incomplete tear of CFL; and Grade III, severe with complete tear of ATFL and CFL. Grades I and II respond well to functional treatment. Functional treatment includes RICE protocol, i.e., rest, ice, compression, and elevation. It also includes range of motion and strengthening exercises, proprioceptive training, and sports-specific exercises. Bracing and taping of the ankle joint help in preventing the sprains and also reduce the recurrence of the injury. Grade III ankle injury may be treated with surgery if the symptoms persist post functional treatment. The guidelines provided for the treatment of ankle sprains are of general validity, but each athlete is different with different needs. Hence, a personalized exercise protocol should be followed to achieve best results.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/70162",risUrl:"/chapter/ris/70162",signatures:"Rachana Dabadghav",book:{id:"9413",title:"Essentials in Hip and Ankle",subtitle:null,fullTitle:"Essentials in Hip and Ankle",slug:"essentials-in-hip-and-ankle",publishedDate:"July 29th 2020",bookSignature:"Carlos Suarez-Ahedo, Anell Olivos-Meza and Arie M. Rijke",coverURL:"https://cdn.intechopen.com/books/images_new/9413.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"235976",title:"M.D.",name:"Carlos",middleName:null,surname:"Suarez-Ahedo",slug:"carlos-suarez-ahedo",fullName:"Carlos Suarez-Ahedo"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"305115",title:"M.Sc.",name:"Rachana",middleName:null,surname:"Dabadghav",fullName:"Rachana Dabadghav",slug:"rachana-dabadghav",email:"rach.nik25@gmail.com",position:null,institution:null}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Biomechanics",level:"1"},{id:"sec_3",title:"3. Chronic ankle instability (CAI)",level:"1"},{id:"sec_4",title:"4. Mechanical and functional instability",level:"1"},{id:"sec_5",title:"5. Rehabilitation",level:"1"},{id:"sec_5_2",title:"5.1 Reduce pain and swelling",level:"2"},{id:"sec_5_3",title:"5.1.1 Rest",level:"3"},{id:"sec_6_3",title:"Table 1.",level:"3"},{id:"sec_7_3",title:"5.1.3 Compression and elevation",level:"3"},{id:"sec_9_2",title:"5.2 Improve range of motion (ROM)",level:"2"},{id:"sec_9_3",title:"5.2.1 Range of motion exercises",level:"3"},{id:"sec_10_3",title:"5.2.2 Manual therapy",level:"3"},{id:"sec_12_2",title:"5.3 Improve strength",level:"2"},{id:"sec_13_2",title:"5.4 Improve proprioception and balance",level:"2"},{id:"sec_14_2",title:"5.5 Sports-specific training",level:"2"},{id:"sec_15_2",title:"5.6 Criteria for return to sports",level:"2"},{id:"sec_16_2",title:"5.7 Taping and bracing",level:"2"},{id:"sec_18",title:"6. Grade III lateral ankle sprains",level:"1"},{id:"sec_19",title:"7. Conclusion",level:"1"}],chapterReferences:[{id:"B1",body:'\nYeung M, Chan K, So C, Yuan W. An epidemiological survey on ankle sprain. British Journal of Sports Medicine. 1994;28(2):112-116\n'},{id:"B2",body:'\nKobayashi T, Gamada K. Lateral ankle sprain and chronic ankle instability. Foot & Ankle Specialist. 2014;7(4):298-326\n'},{id:"B3",body:'\nChan KW, Ding BC, Mroczek KJ. Acute and chronic lateral ankle instability in the athlete. Bulletin of the NYU Hospital for Joint Diseases. 2011;69(1):17-26\n'},{id:"B4",body:'\nLynch SA. Assessment of injured ankle in the athletes. Journal of Athletic Training. 2002;37(4):406-412\n'},{id:"B5",body:'\nFerran N, Maffulli N. Epidemiology of sprains of the lateral ankle ligament complex. Foot and Ankle Clinics. 2006;11(3):659-662\n'},{id:"B6",body:'\nAlanen V, Taimela S, Kinnunen J, Koskinen S, Karaharju E. Incidence and clinical significance of bone bruises after supination injury of the ankle. The Journal of Bone and Joint Surgery British. 1998;80-B(3):513-515\n'},{id:"B7",body:'\nDananberg H, Shearstone J, Guillano M. Manipulation method for the treatment of ankle equinus. Journal of the American Podiatric Medical Association. 2000;90(8):385-389\n'},{id:"B8",body:'\nHetherington B. Lateral ligament strains of the ankle, do they exist? Manual Therapy. 1996;1(5):274-275\n'},{id:"B9",body:'\nHocutt J, Jaffe R, Rylander C, Beebe J. Cryotherapy in ankle sprains. The American Journal of Sports Medicine. 1982;10(5):316-319\n'},{id:"B10",body:'\nCapasso G, Maffulli N, Testa V. Ankle taping: Support given by different materials. British Journal of Sports Medicine. 1989;23(4):239-240\n'},{id:"B11",body:'\nMaitland GD. Peripheral Manipulation. 2nd ed. Sydney, New South Wales, Australia: Butterworths; 1977. p. 282\n'},{id:"B12",body:'\nMulligan B. “NAGS”, “SNAGS”, “MWMS”, etc. Wellington, NZ: Plane View Press; 1995\n'},{id:"B13",body:'\nVan Dijk CN. CBO-guideline for diagnosis and treatment of the acute ankle injury. National Organization for Quality Assurance in Hospitals. Nederlands Tijdschrift voor Geneeskunde. 1999;143(42):2097-2101\n'},{id:"B14",body:'\nWilkerson GB, Pinerola JJ, Caturano RW. Invertor vs. evertor peak torque and power deficiencies associated with lateral ankle ligament injury. The Journal of Orthopaedic and Sports Physical Therapy. 1997;26:78-86\n'},{id:"B15",body:'\nBaumhauer JF, Alosa DM, Renström FH, Trevino S, Beynnon B. A prospective study of ankle injury risk factors. American Journal of Sports Medicine. 1995;223:564-570\n'},{id:"B16",body:'\nKnight KL. Knee rehabilitation by the daily adjustable progressive resistive exercise technique. The American Journal of Sports Medicine. 1979;7:336-337\n'},{id:"B17",body:'\nPerrin DH, Gieck JH. Principles of therapeutic exercise. In: Perrin DH, editor. The Injured Athlete. 3rd ed. Philadelphia, PA: Lippincott-Raven; 1999. pp. 123-139\n'},{id:"B18",body:'\nVerhagen E, van der Beek A, Twisk J, Bouter L, Bahr R, van Mechelen W. The effect of a proprioceptive balance board training program for the prevention of ankle sprains. The American Journal of Sports Medicine. 2004;32(6):1385-1393\n'},{id:"B19",body:'\nDabadghav R. Correlation of ankle eversion to inversion strength ratio and static balance in dominant and non-dominant limbs of basketball players. Journal of Sports Medicine and Physical Fitness. 2016;56(4):422-427\n'},{id:"B20",body:'\nHardy L, Huxel K, Brucker J, Nesser T. Prophylactic ankle braces and star excursion balance measures in healthy volunteers. Journal of Athletic Training. 2008;43(4):347-351\n'},{id:"B21",body:'\nKase K, Tatsuyuki H, Tomoki O. Development of Kinesio™ tape Kinesio™ taping perfect manual. Kinesio Taping Association. 1996;6-10:117-118\n'},{id:"B22",body:'\nMurray H. Effects of Kinesio™ Taping on Muscle Strength After ACL-Repair. Journal of Orthopaedic and Sports Physical Therapy. 2000;30:1-3. Available from: https://performance.nd.edu/assets/114689/kinesio_study_acl_repair.pdf [Accessed: 31 July 2019]\n'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Rachana Dabadghav",address:"rach.nik25@gmail.com",affiliation:'
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