nociceptorns

Nociceptors, sometimes misspelled as nociceptorns, are specialized sensory neurons that detect potentially harmful stimuli and initiate the perception of pain. They are free nerve endings of small-diameter primary afferent neurons located in peripheral tissues such as the skin, joints, mucous membranes, and various organs; they are not typically found in healthy brain tissue. Most nociceptors are polymodal, responding to mechanical damage, extreme temperatures, and chemical mediators released by injured tissue.

Nociceptors are broadly categorized by conduction velocity and fiber type into A-delta fibers and C fibers. A-delta fibers are thinly myelinated and convey fast, sharp pain, whereas C fibers are unmyelinated and carry slower, duller pain. Receptors and ion channels expressed by nociceptors include TRPV1, TRPA1, ASICs, and other mechanosensitive channels, which transduce different modalities of noxious stimuli.

Peripheral terminals release neuropeptides such as substance P and calcitonin gene-related peptide (CGRP), contributing to local neurogenic inflammation. The cell bodies of nociceptors reside in dorsal root or cranial nerve ganglia, and their central processes enter the spinal cord, projecting mainly to the dorsal horn (lamina I and II) before sending signals via ascending pathways such as the spinothalamic tract to the thalamus and cerebral cortex, as well as to brainstem and limbic structures.

Injury and inflammation can cause peripheral sensitization, lowering nociceptor thresholds, while ongoing input can lead to central sensitization, amplifying pain signals. Clinically, nociceptor signaling is a major target of analgesia, with NSAIDs reducing peripheral sensitization and local anesthetics blocking nerve conduction. Ongoing research explores nociceptor subtypes and their roles in chronic pain conditions, including inflammatory, neuropathic, and migraine pain.