Nociceptor

Nociceptors are sensory neurons that detect potentially damaging stimuli and initiate nociception, the neural processes that underlie the sensation of pain. They are free nerve endings of small-diameter neurons located throughout the peripheral nervous system, including the skin and mucous membranes, as well as deep tissues such as joints, muscles, and visceral organs.

There are two main functional classes: A-delta fibers, which are thinly myelinated and convey fast, sharp pain, and C fibers, which are unmyelinated and convey slower, dull, diffuse pain. Polymodal nociceptors respond to mechanical, thermal, and chemical stimuli, while some subsets show preferences for a particular modality.

Transduction occurs when stimuli gate ion channels in the peripheral terminals, generating electrical signals that travel via the dorsal root or cranial nerve ganglia to the dorsal horn of the spinal cord and onward to brain regions such as the thalamus and somatosensory cortex. Key transduction channels include members of the TRP family (for example, TRPV1 for heat and capsaicin, TRPA1 for chemical irritants) and other mechanosensitive channels such as ASICs.

Inflammation or tissue injury releases mediators like prostaglandins, bradykinin, and nerve growth factor that sensitize nociceptors, lowering their thresholds and increasing responsiveness—peripheral sensitization. Repeated or intense input can lead to central sensitization, amplifying pain beyond the original injury and contributing to hyperalgesia and allodynia.

Clinical relevance includes analgesic strategies that target nociceptors or their signaling pathways, such as NSAIDs reducing prostaglandin synthesis, local anesthetics blocking voltage-gated sodium channels, and topical or systemic agents that desensitize nociceptors.