Abstract
Brachial plexus injuries are commonly followed by chronic pain, mostly with neuropathic characteristics. This is due to peripheral nerve lesions, particularly nerve root avulsions, as well as upper limb amputations, and complex regional pain syndrome (CRPS). The differential diagnosis between CRPS and neuropathic pain is essential as the treatment is different for each of them. Medical treatments are the first step, but for refractory cases there are two main types of surgical alternatives: ablative techniques and neuromodulation. The first group involves destruction of the posterior horn deafferented neurons and usually provides a better pain control but has a 10% complication rate. The second group provides pain control with function preservation but with limited effectiveness. Each case has to be thoroughly evaluated to apply the treatment modality best suited for it.
Keywords
- brachial plexus injury
- brachial plexus avulsion
- chronic pain
- neuropathic pain
- deafferentation pain
- phantom pain
- pulsed radiofrequency
- peripheral nerve stimulation
- neuromodulation
- DREZ-otomy
1. Introduction
Brachial plexus injuries are associated not only with motor and sensory functional impairment [1] but also with chronic pain in the affected upper limb [2, 3, 4, 5, 6, 7]. Most of these injuries are due to motor vehicle accidents, particularly motorbikes [1, 5], but a few of them can occur due to iatrogenia [8, 9, 10, 11, 12, 13, 14, 15, 16], particularly during lymph node biopsy [17, 18] or treatment of some malignancies [19].
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2. Incidence
Although 50–82.7% of brachial plexus injuries suffer from chronic pain [2, 3, 5, 6, 17, 35, 49, 50, 51], it is severe in 41% of them [32]. The incidence and severity are higher in nerve root avulsions [2, 3, 4, 7, 21, 30, 33], especially when all the roots are avulsed [2, 17, 21]. Overtime there is a spontaneous progressive improvement, so just after the injury 90% of patients suffer from pain but affects only 30% of them 3 years later [35, 36, 49].
Brachial plexus injuries may also be accompanied by partial or complete traumatic upper limb amputation. About
3. Pathophysiology
The neuropathic pain is induced by an injury to the somatosensory pathways [56, 57] like a brachial plexus injury, an upper limb amputation or both of them simultaneously [2, 7, 58].
The peripheral nerve injury induces deafferentation [2] and damage to the C nerve fibres [59]. The dorsal horn neurons devoid of their peripheral sensorial input start to fire spontaneously and erratically [60, 61, 62, 63, 64], stimulating pain sensation in the higher central nervous system levels [65, 66]. In experimental studies it has been found that the spinal cord microglia and astrocytes are activated at the injury site [67] and help to maintain the neuropathic pain [68, 69, 70, 71, 72]. Higher levels like the thalamus and the motor cortex also undergo the same process by which deafferented neurons create new synapses and reorganize and start firing in abnormal patterns [7, 73, 74, 75, 76, 77]. Descending pathways modulate the neuropathic pain [78] creating new circuits that induce and maintain it [79, 80, 81]. The brain and spinal cord neuronal reorganization leads to an increased sensitivity to otherwise normal stimuli, lowering the threshold required to feel the sensation as pain and inducing secondary hyperalgesia and allodynia [4, 82]. It also explains why the pain often extends beyond the denervated area [26, 33] and why it manifests at the border areas between the partially denervated and normal dermatomes [17, 27].
As mentioned above the pain seen after brachial plexus injury has two distinct patterns: paroxysmal and continuous. The first one is thought to originate from the deafferented posterior spinal horn neurons [60, 83], while the second one comes from the thalamus [74, 84]. In the phantom limb pain, the brain cortex undergoes a functional reorganization in response to the chronic pain [40, 85, 86].
Some have suggested that the neuropathic pain after brachial plexus avulsion is generated not by the avulsed nerve roots but by the remaining ones [67] that are also injured, although not so severely [34]. Although this might be true in some cases, it does not explain why the neuropathic pain severity is maximal when all nerve roots are avulsed [2, 17, 21, 55].
4. Medical treatment
This kind of pain, particularly in case of nerve root avulsions, is difficult to treat due to partial responses and frequent relapses [5, 6, 17]. The response to pharmacological treatments decreases when the pain intensity increases [6].
The non-steroidal anti-inflammatory drugs (NSAIDs) are of little help in the chronic phase [17, 30].
The first step is
The second step is the combination of the above-mentioned drugs with anti-epileptic agents [89], like
Other drugs have been tried experimentally in rats, like rapamycin [94], intrathecal Trichostatin A (TSA) [94] or intravenous immunoglobulin [95], but there are no reports of their use in humans.
The common clinical features shared by neuropathic pain and CRPS hinder a pure clinical diagnosis [6]. Distinguishing between both of them is essential as the latter causes greater disabilities [99]. To differentiate them, an ultrasound examination can be performed, as the muscular architecture is preserved in neuropathic pain but not in CRPS [99].
Medical treatments can also classify the pain:
5. Surgical treatment
Brachial plexus injury repair by direct suture, by grafts or by nerve transfers, particularly sensory nerve transfers, minimizes the incidence and severity of neuropathic pain [4, 26, 34, 67, 104, 105, 106, 107, 108, 109], and the sooner the repair is done the better [25, 67]. CRPS is the exception as further surgery outside trapped nerve decompression seems to have a negative impact on the outcome [101]. In these cases either an interscalene [102] or stellate ganglion block [110] or a cervical spinal cord stimulator [111, 112, 113] is recommended instead. The phantom limb pain only improves with central nervous system procedures [114, 115].
There are two main roads of action: neuromodulation and ablative procedures. The first group relies on applying electric impulses to different areas of the central or peripheral nervous system, aiming to block the transmission of the nerve impulses that are finally interpreted as pain in the sensory motor cortex. They are particularly effective for continuous pain but less so for paroxysmal painful discharges [84]. The ablative procedures aim to destroy the posterior horn spinal cord neurons that start to fire in an abnormal way after being disconnected from their peripheral sensory input [25, 64, 65, 66], controlling paroxysmal pain better than continuous pain [84].
5.1. Neuromodulation procedures
In small clinical series of patients,
In neuropathic pain induced by brachial plexus injury,
5.2. Ablative procedures
The medial thalamotomy, the spinothalamic tractotomy, and the anterolateral tractotomy have been abandoned due to the limited pain control they provide and the side effects they carry [119].
The DREZ is an anatomical area of the spinal cord composed by the dorsal rootlets, Lissauer’s tract and the dorsal horn [25].
Lack of DREZ region damage confirmed in preoperative MRI seems to be an indicator of successful pain control with the DREZ procedure to the point that no patient with spinal cord dorsal horn abnormalities had a completely pain-free outcome [22]. It is suggested that if the posterior horn is abnormal, the thalamus will most likely develop deafferented neurons that will start firing in an abnormal pattern and thus the treatment should be directed there and not to the spinal cord [22]. This observation contradicts the fact that surgically amputated patients due to different medical conditions in whom a normal spinal cord anatomy is preserved fare worse with the DREZ operation than those that had a traumatic amputation [115]. In these DREZ-otomy failed cases, a cervical spinal cord stimulator is recommended [113]. Post-operative MRI examinations in radiofrequency DREZ lesions have shown that the surgically lesioned area extends beyond the posterior horn [149]. This is in concordance with the clinical fact that some patients develop post-operative leg weakness, ataxia and sensory abnormalities below the operated area [22, 23, 24, 28, 48, 133, 140, 141].
DREZ-otomy provides 83% pain control rate in phantom pain [115, 150, 151], 67% in burning pain and 29% for stump pain [115, 152]. Both amputation and nerve root avulsion phantom pain seem to benefit from DREZ-otomies [115, 150, 151]. The results in pain improvement are better in traumatic amputations than in those due to medical conditions [28, 115]. Some researchers recommend to start with neurostimulation in phantom limb pain and to recourse to the DREZ-otomy as a last resort [152].
The DREZ-otomy can be created microsurgicaly (Sindou’s technique) [25], with radiofrequency (Nashold’s technique) [29, 48], with laser [153, 154, 155, 156] or even with an ultrasonic microprobe [131], but there are no major differences in pain control or patients’ quality of life between them [142, 156]. The microsurgical technique is performed with the regular bipolar forceps, which is less expensive than the other options (radiofrequency, laser, ultrasonic probe), making it ideal for countries with limited resources [144, 157]. Some scientists have attempted intraoperative neurophysiological monitoring to improve the clinical results [65, 158, 159]. Freeing the spinal cord completely helps to stop pain induction with neck movements [25]. A concern that has not yet been studied in detail is the possible long-term effects of extensive cervical laminectomies required for the procedure, as it might accelerate cervical kyphotic deformity with cervical spinal cord myelopathy [147]. In any case the original full bilateral cervical C5-T1 laminectomies [25, 140] have been replaced in many surgical units by hemi-laminectomies.
6. Conclusions
Brachial plexus injuries can be the source of chronic pain. This pain can be neuropathic, CRPS and/or phantom limb, particularly if there is extensive nerve root avulsion or an upper limb amputation. The pain is oftentimes excruciating and leads to a bad quality of life even interfering with the physiotherapy needed to achieve a good recovery. The response to treatment of this pain is not always as successful as expected. Some patients respond to medication, but many need neuromodulation or ablative procedures. The most effective surgical technique is the DREZ-otomy, but 10% of patients develop side effects. If the ablative procedures fail, cervical spinal cord stimulation can be attempted.
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