✓ Transduction—stimulation of nociceptors.
❖ Nociceptors found in both somatic and visceral structures, are activated by mechanical, thermal, and chemical stimuli. Noxious stimuli may cause release of cytokines and chemokines that sensitize and/or activate nociceptors.
✓ Conduction—Receptor activation leads to action potentials that continue along afferent fibers to the spinal cord. Stimulation of large-diameter, sparsely myelinated fibers evokes sharp, well-localized pain. Stimulation of small-diameter, unmyelinated fibers produces aching, poorly localized pain.
✓ Transmission—Afferent nociceptive fibers synapse in the spinal cord’s dorsal horn, releasing excitatory neurotransmitters (eg, glutamate and substance P). The spinothalamic tract and other pathways bring the signal to the brain’s higher cortical structures.
✓ Perception—The experience of pain occurs when signals reach higher cortical structures. Relaxation, meditation, and distraction can lessen pain, and anxiety and depression can worsen pain.
✓ Modulation—Possible modulating factors include glutamate, substance P, endogenous opioids, γ-aminobutyric acid (GABA), norepinephrine, and serotonin.