Wei Hong, Pertovaara Antti
Biomedicum Helsinki, Institute of Biomedicine/Physiology, POB 63, 00014 University of Helsinki, Finland.
Eur J Pharmacol. 2006 Mar 27;535(1-3):157-65. doi: 10.1016/j.ejphar.2006.02.019. Epub 2006 Mar 6.
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.
研究了延髓和脊髓5-羟色胺（5-HT）1A受体在神经性超敏反应内源性调节中的作用。5-HT1A受体拮抗剂WAY-100635经延髓头端腹内侧或皮下给药时，可减轻脊髓神经损伤大鼠的机械性超敏反应。延髓内侧或皮下注射WAY-100635对损伤区域以外的热或机械性伤害感受没有影响。鞘内注射WAY-100635对疼痛相关行为无显著影响。鞘内注射WAY-100635或α2-肾上腺素能受体拮抗剂阿替美唑可逆转延髓内侧注射WAY-100635引起的机械性超敏反应抑制，但阿片受体拮抗剂纳洛酮则不能。结果表明，5-HT的内源性释放通过作用于延髓内侧的5-HT1A受体，对神经性动物的下行抑制起紧张性抑制作用。在延髓内侧给予5-HT1A受体拮抗剂后，下行性疼痛调节通路的抑制解除。这导致神经性超敏反应的选择性减轻，这是由于其对脊髓5-HT1A受体和α2-肾上腺素能受体的作用。
