The role of 5-hydroxytryptamine (5-HT) receptor subtypes and plasticity in the 5-HT systems in the regulation of nociceptive sensitivity.
This review shows that the role of 5-hydroxytryptamine (5-HT) in the regulation of nociception depends on the 5-HT receptor subtypes involved and on long-term functional changes in the 5-HT receptors. Stimulation of the 5-HT1 receptors, as well as of the 5-HT2 and 5-HT3 receptors, may reduce nociceptive sensitivity. In addition, activation of 5-HT2 and 5-HT3 receptors may also enhance nociceptive sensitivity. Up- or down-regulation of the 5-HT receptors may result in long-lasting changes, plasticity, in the 5-HT systems. Lesioning of 5-HT neurons induces denervation supersensitivity to 5-HT, and prolonged stimulation of 5-HT receptors may produce subsensitivity to 5-HT. In the spinal cord denervation supersensitivity to 5-HT may depend on reduced release of substance P (SP). An increase in the release of SP, on the other hand, may reduce the effects of 5-HT receptor activation. Long-term treatment with antidepressants which are used in clinical pain therapy appears to up-regulate the 5-HT1 receptors and to down-regulate the 5-HT2 receptors.
Eide
P K
PK
Department of Physiology, University of Bergen, Norway.
Hole
K
K
D000818:Animals; D003714:Denervation; D006801:Humans; D009619:Nociceptors / Q000502:physiology*; D011985:Receptors, Serotonin / Q000145:classification / Q000502:physiology*; D013268:Stimulation, Chemical; D013373:Substance P / Q000502:physiology
D011985:Receptors, Serotonin; D013373:Substance P