Pharmacology of Pain Transmission and Modulation

Abstract

Pain is transmitted to the central nervous system via thinly myelinated Aδ and unmyelinated C-fibers. The former convey the sensation of sharp, lancinating “first” pain, whereas the latter conduct the dull, longer-lasting “second” pain. Aδ-fibers predominantly respond to mechanical stimuli (Type I or “high-threshold mechanoreceptor”) or to noxious heat (Type II). Conversely, the C-fibers are polymodal, the same fiber responding to mechanical, thermal and chemical stimuli. Both Aδ- and C-fibers terminate in the superficial dorsal horn, mainly in Rexed Laminae I and II, although some Aδ-fibers also terminate in the deeper lamina V. In the periphery, the distal endings terminate freely in the tissues. These free nerve endings express a variety of signal transducing molecules, one of the most extensively investigated being the transient receptor potential ion channel TRPV1, also known as the capsaicin receptor [1].