Functional Anatomy of Muscle: Muscle, Nociceptors and Afferent Fibers

Abstract

Nociceptors are free nerve endings, but not all free nerve endings in skeletal muscle are nociceptive. Nociceptive free nerve endings are connected to the CNS by thin myelinated fibers or unmyelinated afferent fibers. In the light microscope, free nerve endings look like a string of beads, i.e., they consist of axonal expansions (varicosities) connected by thin axonal segments. The neuropeptide substance P has been reported to be present predominantly in nociceptive afferent fibers. In the electron microscope, a prominent feature of nociceptive nerve endings is that they are not free in the strict sense but ensheathed by Schwann cells. At present, there are no clear ultrastructural differences between non-nociceptive free nerve endings (e.g., sensitive mechanoreceptors and thermoreceptors) and nociceptive ones. Functionally, different free nerve endings are assumed to possess different sets of receptor molecules in their axonal membrane. Receptor molecules that are particularly important for the function of muscle nociceptors are acid-sensing ion channels (ASICs) that open at a low tissue pH, P2X3 receptors that are activated by binding adenosine triphosphate (ATP), and the transient receptor potential receptor subtype 1 (TRPV1) that is sensitive to high temperatures and low pH.