nociceptorit

Nociceptorit are specialized sensory neurons that detect noxious or potentially damaging stimuli and initiate nociception, the neural processes that encode and transmit information about tissue damage. They are located in both the skin and internal organs, as well as in muscles and joints. The term nociception refers to peripheral detection and transmission, while pain is the subjective experience that may follow.

Most nociceptors are small-diameter fibers, classed as A-delta and C fibers. A-delta fibers carry fast, well-localized sharp pain, whereas C fibers convey slow, dull, burning pain. Nociceptors respond to specific modalities: mechanical, thermal, or chemical, and some are polymodal, responding to multiple stimuli. Silent nociceptors exist that become active under inflammatory conditions.

Molecularly, nociceptors express ion channels that transduce stimuli, including TRP channels such as TRPV1 (heat/chemical), TRPA1 (chemical irritants), and various mechanosensitive channels, as well as voltage-gated sodium channels such as Nav1.7, Nav1.8, and Nav1.9 that support action potential generation. Peripheral terminals release neuropeptides such as substance P and CGRP upon activation, contributing to vasodilation and sterile inflammation.

Pathophysiology: Nociceptor sensitization during inflammation lowers activation thresholds (peripheral sensitization), increasing responsiveness to stimuli. In the spinal cord, activity can lead to central sensitization, amplifying pain signals and contributing to hyperalgesia and allodynia. In chronic pain conditions, nociceptor function may be persistently altered.

Research aims to target nociceptors for analgesia, including antagonists of specific channels, modulation of inflammatory mediators, and modulation of central pathways. Nociceptors are central to protective reflexes and injury avoidance, but dysregulation can contribute to chronic pain.