5-HT(1A) receptors in endogenous regulation of neuropathic hypersensitivity in the rat.
The role of medullary and spinal 5-HT(1A) receptors in endogenous regulation of neuropathic hypersensitivity was studied. When administered in the rostroventromedial medulla or subcutaneously, WAY-100635, a 5-HT(1A) receptor antagonist, attenuated mechanical hypersensitivity in rats with a spinal nerve injury. Thermal or mechanical nociception outside of the injured area was not influenced by medial medullary or subcutaneous administration of WAY-100635. Intrathecal administration of WAY-100635 had no significant effect on pain-related behavior. Suppression of mechanical hypersensitivity induced by medial medullary administration of WAY-100635 was reversed by intrathecal administration of WAY-100635 or atipamezole, an alpha2-adrenoceptor antagonist, but not by naloxone, an opioid receptor antagonist. The results indicate that endogenous release of 5-HT, via action on medial medullary 5-HT(1A) receptors, tonically suppresses descending inhibition in neuropathic animals. Following medial medullary administration of a 5-HT(1A) receptor antagonist, descending pain regulatory pathways are disinhibited. This leads to selective attenuation of neuropathic hypersensitivity, due to action on spinal 5-HT(1A) receptors and alpha2-adrenoceptors.
Biomedicum Helsinki, Institute of Biomedicine/Physiology, POB 63, 00014 University of Helsinki, Finland.
Hong
H
Wei
Antti
A
Pertovaara
D000317:Adrenergic alpha-Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D006358:Hot Temperature / Q000009:adverse effects; D006930:Hyperalgesia / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology; D007276:Injections, Intraventricular; D007278:Injections, Spinal; D007279:Injections, Subcutaneous; D008297:Male; D009270:Naloxone / Q000008:administration & dosage / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D010146:Pain / Q000209:etiology / Q000503:physiopathology* / Q000517:prevention & control; D010147:Pain Measurement / Q000379:methods; D017288:Pain Threshold / Q000187:drug effects; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology; D011725:Pyridines / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D044282:Receptor, Serotonin, 5-HT1A / Q000502:physiology*; D058829:Serotonin 5-HT1 Receptor Antagonists; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D013127:Spinal Nerves / Q000293:injuries*
D000317:Adrenergic alpha-Antagonists; D007093:Imidazoles; D009292:Narcotic Antagonists; D010879:Piperazines; D011725:Pyridines; D058829:Serotonin 5-HT1 Receptor Antagonists; D012702:Serotonin Antagonists; C050701:atipamezole; D044282:Receptor, Serotonin, 5-HT1A; D009270:Naloxone; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide