Basic Science of Pain: Anatomy, Physiology, and Pharmacology
Nociception and modulation
Pain begins when noxious stimuli activate free nerve endings. A-delta fibers are thinly myelinated and fast, producing sharp pain; C fibers are unmyelinated, slow, and polymodal, producing dull pain. Cell bodies sit in dorsal root ganglia, and central terminals release glutamate and substance P in the dorsal horn. Second-order neurons in laminae I, II, and V cross via the anterior white commissure and ascend in the spinothalamic tract. This explains contralateral loss of pain and temperature with preserved proprioception in a cord lesion. Ascending pathways project to thalamus, insula, anterior cingulate, and somatosensory cortex. Descending inhibition from periaqueductal gray to rostral ventromedial medulla to dorsal horn uses serotonin, norepinephrine, and endogenous opioids, which is why SNRIs and TCAs help.
Peripheral sensitization lowers threshold after injury; central sensitization produces wind-up, long-term potentiation, and spreading hyperalgesia. Neuropathic pain involves ectopic sodium-channel activity and central changes. Key transmitters and receptors include glutamate at AMPA/NMDA, GABA/glycine inhibition, mu/kappa/delta opioid receptors, TRPV1, and sodium channels.
Traps: A-beta fibers are not nociceptors under normal conditions; visceral pain is poorly localized and can refer; dermatomes are sensory while myotomes are motor. Opioid tolerance is not addiction, and physical dependence is expected.
Worked example: a patient loses pinprick and temperature on the left below T6 but vibration and joint position are intact. Localize the lesion to the right spinal cord because spinothalamic fibers cross near their entry level, while dorsal columns ascend ipsilaterally. Rule: sharp-fast-A-delta, dull-slow-C.