Holden J E, Naleway E
Department of Medical-Surgical Nursing, The University of Illinois at Chicago, Chicago, IL 60612-7350, USA.
Brain Res. 2001 Aug 17;911(1):27-36. doi: 10.1016/s0006-8993(01)02567-7.
Electrical stimulation of the lateral hypothalamus (LH) produces antinociception partially blocked by intrathecal alpha-adrenergic antagonists, but the mechanism underlying this effect is not clear. Evidence from immunological studies demonstrates that substance P-immunoreactive neurons in the LH project near the A7 catecholamine cell group, a group of noradrenergic neurons in the pons known to effect antinociception in the spinal cord dorsal horn. Such evidence suggests that LH neurons may activate A7 neurons to produce antinociception. To test this hypothesis, the cholinergic agonist carbachol was microinjected into the LH at doses of 63, 125 and 250 nmol and the resulting effects on tail-flick and nociceptive foot-withdrawal latencies were measured. All three doses significantly increased response latencies on both tests, with the 125-nmol dose providing the optimal effect. Intrathecal injection of the opioid antagonist naltrexone (97 nmol) partially reversed antinociception, but neither the alpha(2)-adrenoceptor antagonist yohimbine nor the alpha(1)-adrenoceptor antagonist WB4101 altered latencies. However, two sequential doses of yohimbine blocked LH-induced antinociception on both tests. In contrast, two sequential doses of WB4101 increased nociceptive responses on both the tail-flick and foot-withdrawal tests. These findings, and those of published reports, suggest that neurons in the LH activate spinally projecting methionine enkephalin neurons, as well as two populations of A7 noradrenergic neurons that exert a bidirectional effect on nociception. One of these populations increases nociception through the action of alpha(1)-adrenoceptors and the other inhibits nociception through the action of alpha(2)-adrenoceptors in the spinal cord dorsal horn.
电刺激下丘脑外侧区（LH）可产生抗伤害感受作用，鞘内注射α-肾上腺素能拮抗剂可部分阻断该作用，但其潜在机制尚不清楚。免疫学研究证据表明，LH中P物质免疫反应性神经元投射至A7儿茶酚胺细胞群附近，A7是脑桥中的一组去甲肾上腺素能神经元，已知其可影响脊髓背角的抗伤害感受。这些证据表明，LH神经元可能激活A7神经元以产生抗伤害感受。为验证这一假设，将胆碱能激动剂卡巴胆碱以63、125和250 nmol的剂量微量注射到LH中，并测量其对甩尾和伤害性足退缩潜伏期的影响。所有三个剂量均显著增加了两项测试的反应潜伏期，其中125 nmol剂量的效果最佳。鞘内注射阿片类拮抗剂纳曲酮（97 nmol）可部分逆转抗伤害感受作用，但α₂-肾上腺素能拮抗剂育亨宾和α₁-肾上腺素能拮抗剂WB4101均未改变潜伏期。然而，连续两次注射育亨宾可阻断LH诱导的两项测试中的抗伤害感受作用。相反，连续两次注射WB4101可增加甩尾和足退缩测试中的伤害性反应。这些发现以及已发表报告的结果表明，LH中的神经元激活了向脊髓投射的甲硫氨酸脑啡肽神经元，以及对伤害感受具有双向作用的两类A7去甲肾上腺素能神经元。其中一类通过α₁-肾上腺素能受体的作用增强伤害感受，另一类通过脊髓背角中α₂-肾上腺素能受体的作用抑制伤害感受。
