Neurobiology of Pain and Pain Mechanisms
What you must know
Trace the pain pathway: nociceptor transduction (TRP channels, acid-sensing channels) to primary afferent to dorsal horn/caudalis synapse (glutamate, substance P, CGRP) to ascending spinothalamic and trigeminothalamic tracts to thalamus and cortex. Understand the gate control theory (A-beta input inhibits nociceptive transmission via interneurons) and descending inhibition from the periaqueductal gray through the rostral ventromedial medulla. Know the difference between nociceptive, inflammatory, neuropathic, and nociplastic pain.
Mechanisms
Peripheral sensitization involves inflammatory mediators (bradykinin, prostaglandins, cytokines) lowering nociceptor threshold. Central sensitization involves NMDA receptor activation, wind-up, and long-term potentiation in the dorsal horn. Ectopic discharges and altered sodium channel expression underlie neuropathic pain. Loss of descending inhibition and altered central processing characterize nociplastic pain such as fibromyalgia-like presentations.
Traps
Questions test whether you can distinguish mechanisms by history: neuropathic pain often has burning, lancinating, or electric qualities with sensory change; nociplastic pain is widespread, disproportionate, and not explained by lesion. Do not assume all chronic pain is neuropathic. Wind-up is a spinal phenomenon, not a peripheral one. Opioid-induced hyperalgesia is a distinct trap from tolerance.
Worked example
A patient reports burning tongue pain with no visible lesion, normal imaging, and pain provoked by light touch. Allodynia plus burning suggests neuropathic mechanisms (ectopic activity and central sensitization), not simple nociception. Treatment logic shifts toward membrane stabilizers rather than pure analgesics.
Rule of thumb
Name the mechanism before naming the drug: nociceptive → NSAIDs/opioids; neuropathic → gabapentinoids/tricyclics; nociplastic → centrally acting and behavioral approaches.