Ossipov M H, Kovelowski C J, Wheeler-Aceto H, Cowan A, Hunter J C, Lai J, Malan T P, Porreca F
Department of Pharmacology, University of Arizona Health Sciences Center, Tucson, USA.
J Pharmacol Exp Ther. 1996 May;277(2):784-8.
The present experiments explored the role of endogenous opioids in the behavioral response to a formalin-induced nociceptive stimulus in the rat. Flinching was taken as a measure of the intensity of the nociceptive stimulus after the administration of formalin into the dorsal surface of the paw of control animals, or in animals receiving i.p. administration of receptor-selective doses of opioid antagonists including naloxone, naltrindole (delta opioid antagonist), nor-binaltorphimine (kappa opioid antagonist) or beta-funaltrexamine (mu opioid antagonist). Additionally, antisera to [Leu5]enkephalin, [Met5]enkephalin and dynorphin A (1-13) (dynorphin) were administered intrathecally before formalin to explore the contribution of endogenous opioids in modulation of the flinching response. Formalin-induced flinching was increased significantly by naloxone, and receptor selective doses of naltrindole and nor-binaltorphimine, but not beta-funaltrexamine. Additionally, antisera to [Leu5]enkephalin and dynorphin also resulted in a significant increase in formalin-induced flinching, whereas antisera to [Met5]enkephalin had no effect. On the basis of significant increases in formalin-induced flinching produced by 1) receptor-selective doses of delta and kappa, but not mu, opioid antagonists and 2) antisera to [Leu5]enkephalin and dynorphin A, but not [Met5]enkephalin, these data suggest the presence of an opioid inhibitory tone which acts to limit the intensity of the pain signal. This tone appears to be mediated via activation of delta and kappa receptors, possibly by a [Leu5]enkephalin- and dynorphin-like substance, respectively.
本实验探究了内源性阿片类物质在大鼠对福尔马林诱导的伤害性刺激的行为反应中的作用。将福尔马林注射到对照动物爪背或腹腔注射受体选择性剂量阿片类拮抗剂（包括纳洛酮、纳曲吲哚（δ阿片类拮抗剂）、 nor-环丙甲羟二氢吗啡酮（κ阿片类拮抗剂）或β-氟奈曲胺（μ阿片类拮抗剂））的动物后，以缩腿作为伤害性刺激强度的指标。此外，在注射福尔马林前鞘内注射针对亮氨酸脑啡肽、甲硫氨酸脑啡肽和强啡肽A（1-13）（强啡肽）的抗血清，以探究内源性阿片类物质在调节缩腿反应中的作用。纳洛酮、纳曲吲哚和nor-环丙甲羟二氢吗啡酮的受体选择性剂量可显著增加福尔马林诱导的缩腿反应，但β-氟奈曲胺则无此作用。此外，针对亮氨酸脑啡肽和强啡肽的抗血清也可显著增加福尔马林诱导的缩腿反应，而针对甲硫氨酸脑啡肽的抗血清则无作用。基于1）δ和κ（而非μ）阿片类拮抗剂的受体选择性剂量以及2）针对亮氨酸脑啡肽和强啡肽A（而非甲硫氨酸脑啡肽）的抗血清均可显著增加福尔马林诱导的缩腿反应，这些数据表明存在一种阿片类抑制性调节机制，其作用是限制疼痛信号的强度。这种调节机制似乎分别通过激活δ和κ受体介导，可能分别由一种亮氨酸脑啡肽样物质和强啡肽样物质介导。
