Central Mechanisms The Spinal Cord and Referred Pain The axons of primary afferent nociceptors enter the spinal cord via the dorsal root. They terminate in the dorsal horn of the spinal gray matter (Fig. 12-3). The terminals of primary afferent axons contact spinal neurons that transmit the pain signal to brain sites involved in pain perception. When primary afferents are activated by noxious stimuli, they release neurotransmitters from their terminals that excite the spinal cord neurons. The major neurotransmitter they release is glutamate, which rapidly excites dorsal horn neurons. Primary afferent nociceptor terminals also release peptides, including substance P and calcitonin. | Chapter 012. Pain Pathophysiology and Management Part 3 Central Mechanisms The Spinal Cord and Referred Pain The axons of primary afferent nociceptors enter the spinal cord via the dorsal root. They terminate in the dorsal horn of the spinal gray matter Fig. 12-3 . The terminals of primary afferent axons contact spinal neurons that transmit the pain signal to brain sites involved in pain perception. When primary afferents are activated by noxious stimuli they release neurotransmitters from their terminals that excite the spinal cord neurons. The major neurotransmitter they release is glutamate which rapidly excites dorsal horn neurons. Primary afferent nociceptor terminals also release peptides including substance P and calcitonin gene-related peptide which produce a slower and longer-lasting excitation of the dorsal horn neurons. The axon of each primary afferent contacts many spinal neurons and each spinal neuron receives convergent inputs from many primary Skin Source Fauci AS Kasper DL Èraunwald E Hauser SL Longo DL Jameson JL Loscalzo J Harrison s Principles of Internal Medicine 17th Edition http w vv a cats sm e dici n e. co m afferents. - The convergence-projection hypothesis of referred pain. According to this hypothesis visceral afferent nociceptors converge on the same pain-projection neurons as the afferents from the somatic structures in which the pain is perceived. The brain has no way of knowing the actual source of input and mistakenly projects the sensation to the somatic convergence of sensory inputs to a single spinal pain-transmission neuron is of great importance because it underlies the phenomenon of referred pain. All spinal neurons that receive input from the viscera and deep musculoskeletal structures also receive input from the skin. The convergence patterns are determined by the spinal segment of the dorsal root ganglion that supplies the afferent innervation of a structure. For example the afferents that supply the central .