Anatomy, Physiology, and Neurobiology of Pain
From nociceptor to dorsal horn
Pain begins at free nerve endings transduced by ion channels such as TRPV1, acid-sensing channels, and voltage-gated sodium channels (Nav1.7, Nav1.8). A-delta fibers are thinly myelinated and signal fast, sharp "first pain." C fibers are unmyelinated, polymodal, and produce slow, dull "second pain." A-beta fibers are low-threshold mechanoreceptors, not nociceptors, a frequent distractor.
C fibers terminate mainly in laminae I–II (substantia gelatinosa); A-delta fibers terminate in laminae I, II, and V. Wide-dynamic-range neurons in lamina V receive convergent somatic and visceral input, explaining referred pain and dermatomal patterns. Glutamate drives fast transmission; substance P, CGRP, and BDNF modulate it. Repeated input produces wind-up and central sensitization through NMDA receptor activation, clinically manifesting as allodynia and hyperalgesia.
Ascending and descending pathways
Second-order neurons decussate within one to two segments and ascend in the spinothalamic tract, which carries pain and temperature; the dorsal columns carry vibration and proprioception. Spinoreticular and spinomesencephalic fibers contribute arousal and affective dimensions. Descending inhibition runs from periaqueductal gray to the rostral ventromedial medulla, using serotonin and norepinephrine, the rationale for SNRIs and TCAs.
Visceral pain travels with sympathetic fibers from thoracic and upper lumbar viscera and with parasympathetic fibers from pelvic viscera; it is poorly localized and often referred. Somatic pain is well localized.
Trap: because the spinothalamic tract crosses near entry, a cord lesion causes contralateral loss beginning one to two segments below. Another trap: sympathetically maintained pain is not synonymous with complex regional pain syndrome.
Rule of thumb: A-delta means fast, sharp, and well localized; C means slow, dull, and aching.