ABSTRACT
Muscular unmyelinated (C-) fibers are supposed to be the afferent limb of acupuncture effects. Of muscular unmyelinated afferent receptors, polymodal receptors are considered to be important because of their sensitivities to moderate mechanical and strong thermal stimulations and to algesic substances. I would like to introduce response characteristics of muscular polymodal receptors, especially on their sensitization to mechanical stimulation.Polymodal receptors consist of 50% of mechano-sensitive muscular C-fiber receptors in rats. Comparing with non-polymodal receptors that would not respond to heat stimulation, the mechanical threshold of the polymodals is not different, but their discharge rate is lower. The response threshold to heat is around 41°C. The mechanical response of this receptor is augmented by bradykinin, prostaglandins, histamine and acid. Nerve growth factor (NGF) is one of neurotrophic factors that is essential for the development and survival of thin-fiber afferents and their differentiation during ontogeny. In adulthood NGF is produced in inflammatory cells (macrophages, mast cells, etc) and fibroblasts, and sensitizes nociceptors to heat and mechanical stimulations, and plays an important role in hyperalgesia. It is reported that intramuscular injection of NGF into humans induced mechanical hyperalgesia.Recently we found up-regulation of NGF in the muscle in non-inflammatory condition, namely in delayed onset muscle soreness that appears after strenuous and unaccustomed exercise (delayed onset muscle soreness). Up-regulation of NGF in the muscle starts about 12 hrs after exercise, and it lasts up to 2 days after exercise. Anti-NGF antibody injection to the muscle on the 2nd day after exercise, reversed mechanical hyperalgesia. Thus it is concluded that sensitization of C-fiber receptors by NGF to mechanical stimulation results in mechanical hyperalgesia. Because there is no sign of inflammation in the muscle, cells that produce NGF cannot be inflammatory cells, and muscle cells themselves, blood vessel cells or connective tissue cells might produce NGF. In addition, the majority of sensory receptors that are sensitized after exercise are heat sensitive, that means they are mostly polymodal receptors. Because many of muscle pain conditions are not inflammatory, non-inflammatory production of NGF in the muscle observed in the delayed onset muscle soreness raises a possibility that NGF is produced in other muscle pain conditions, and sensitizes muscle nociceptors to result in muscle hyperalgesia. This point must be clarified in future.