Mechanisms of Pain

Pain Transmission

The mechanisms of nociceptive pain are well-defined and provide a foundation for the understanding of other types of pain.18 Following nociceptor stimulation, tissue injury causes the release of substances (bradykinin, serotonin, potassium, histamine, prostaglandins, and substance P) that might further sensitize and/or activate nocicept-ors. Nociceptor activation produces action potentials (transduction) that are transmitted along myelinated Aô-fibers and unmyelinated C-fibers to the spinal cord. The Aô-fibers are responsible for first, fast, sharp pain and release excitatory amino acids that activate a-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors in the dorsal horn. The C-fibers produce second pain, which is described as dull, aching, burning, and diffuse. These nerve fibers synapse in the dorsal horn of the spinal cord, where several neurotransmitters are released including glutamate, substance P, and calcitonin gene-related peptide. Transmission of pain signals continues along the spinal cord to the thalamus, which serves as the pain relay center, and eventually to the cortical regions of the brain where pain is perceived.

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