Group C sensory nerve fiber (C fiber)

Group C sensory nerve fibers, commonly known as **C fibers**, are the smallest-diameter, unmyelinated, slow-conducting afferent fibers within the peripheral and central nervous systems[1][2][3]. They respond to thermal, mechanical, chemical, and pruritic (itch-inducing) stimuli and are polymodal in function. C fibers are especially known for transmitting the dull, burning pain perceived after the initial sharp pain (conveyed by A-delta fibers), as well as warmth, itch, and pleasant touch in subtypes[1][2]. They terminate as free nerve endings in peripheral tissues and connect centrally to the superficial laminae of the dorsal horn in the spinal cord where they contribute to the first stage processing of noxious and thermal stimuli[1][2]. Their activation is relevant to chronic pain, central sensitization, and various neuropathic conditions; they are distinguished from other pain-sensing fibers by their structure (Remak bundles with Schwann cells) and neuropeptide content or isolectin binding (peptidergic/non-peptidergic)[2]. While not a receptor or enzyme, their molecular targets (such as TRPV1, TRPA1, and Mrgprs) serve as drug targets for pain and itch therapies[1][2].

Other names

C fiberUnmyelinated nerve fiberPolymodal nociceptorType IV sensory fiberRemak bundle axon (collective anatomical term)

TRPV1 agonism (activates pain transmission); Blockade of voltage-gated calcium channels (reduces neurotransmitter release, e.g., by gabapentinoids); Inhibition/antagonism of substance P and CGRP signaling (blocks synaptic pain transmission); Desensitization via repeated capsaicin application (reduces pain response).