Muscle pain is a common symptom associated with, for example, myofascial syndrome, fibromyalgia and polymyalgia rheumatica. Many diseases of the muscle tissue are, however, completely or nearly painless such as polymyositis and inclusion body myositis. Thus, a mere inflammation cannot be the cause of muscle pain. In needle electromyography (EMG), the insertion of a needle electrode causes pain but further advancement is usually painless. However, there are small spots of muscle tissue where sudden pain is elicited with the needle. In EMG, these ‘active spots’ are observed to produce spontaneous activity in the form of end plate noise and spikes (EPSs). End plate noise is elicited at the neuromuscular junction of α, β or γ motor neuron. EPSs are action potentials of γ or β motor units. Muscle spindles are the main nociceptors in muscle tissue, both in healthy muscle and in diseases with muscle pain by inflammation of the muscle spindles. Multiple possible mechanisms of muscle pain exist. Polymyalgia rheumatica may have interstitial pain and possibly pain associated with muscle spindle capsules. Delayed onset muscle soreness may reflect both interstitial muscle pain caused by minor injuries and pain generated in mildly inflamed muscle spindles.