Pain-producing (nociceptive) sensory stimuli in skin and viscera activate peripheral nerve endings of primary afferent neurons, which synapse on second-order neurons in spinal cord or medulla (Fig. 5-1). These second-order neurons form crossed ascending pathways that reach the thalamus and project to the somatosensory cortex. Parallel ascending neurons, connecting with brainstem and thalamic nuclei, project to the limbic system and underlie the emotional aspect of pain. Pain transmission is regulated at the dorsal horn level by descending bulbospinal pathways that utilize serotonin, norepinephrine, and several neuropeptides as neurotransmitters.

Agents that modify pain perception may act by reducing tissue inflammation (NSAIDs, prostaglandin synthesis inhibitors), interfering with pain transmission (narcotics), or enhancing descending modulation (narcotics and antidepressants). Anticonvulsants (gabapentin, carbamazepine) may be effective for aberrant pain sensations arising from peripheral nerve injury.