The peripheral apparatus of muscle pain: Evidence from animal and human studies

The peripheral apparatus of muscle pain consists of nociceptors that can be excited by endogenous substances and mechanical stimuli. Histologically, t he nociceptors are free nerve endings supplied by group III (thin myelinate d) and group IV (nonmyelinated) afferents with conduction velocities less t han 30 m/s. At the molecular level, nociceptors have receptors for algesic substances, such as bradykinin, serotonin, and prostagladin E2. The puriner gic receptors and tetrodotoxin-resistant sodium channels might be new impor tant targets for the treatment of muscle pain. Algesic substances (capsaici n, bradykinin, serotonin, potassium chloride, and hypertonic saline) and ot her stimuli (ischemia, strong mechanical stimuli, and electrical stimuli) h ave been shown to induce nociception from muscle in animals and muscle pain in humans. Muscle nociceptors can be sensitized to chemical and mechanical stimuli. Contrary to a former belief, the sensitization is not an unspecif ic process; rather, it is caused by endogenous algesic substances binding t o highly specific receptor molecules in the membrane of the nociceptive end ing. For example, animal studies showed that serotonin sensitizes muscle no ciceptors to chemical and mechanical stimuli. Later, human studies showed t hat serotonin combined with bradykinin induces muscle hyperalgesia to press ure. The sensitization process by endogenous substances that are likely to be released during trauma or inflammatory injury is probably the best estab lished peripheral mechanism for muscle tenderness and hyperalgesia.