Takasaki Ichiro, Nojima Hiroshi, Shiraki Kimiyasu, Kuraishi Yasushi
Division of Molecular Genetics Research, Life Science Research Center, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
Eur J Pharmacol. 2006 Nov 21;550(1-3):62-7. doi: 10.1016/j.ejphar.2006.08.041. Epub 2006 Sep 6.
The analgesic effects of opioid agonists and the expression of mu- and kappa-opioid receptors were compared between mice with herpetic pain and those with postherpetic pain induced by herpetic virus inoculation. Morphine inhibited herpetic pain more effectively than postherpetic pain. Intrathecal injection reduced the analgesic effects of morphine on postherpetic pain, but intracerebroventricular injection did not. The kappa-opioid receptor agonist nalfurafine suppressed herpetic and postherpetic pain to similar degrees. mu-Opioid receptor-like immunoreactivities in the lumbar dorsal horn were markedly decreased at the postherpetic, but not herpetic, stage of pain. In the dorsal root ganglia, the expression of mu-opioid receptor mRNA was significantly decreased in mice with postherpetic pain, whereas the kappa-opioid receptor mRNA level was not altered. These results suggest that specific down-regulation of the mu-opioid receptor in the primary sensory neurons is responsible for the reduced analgesic action of morphine on postherpetic pain. The kappa-opioid receptor may be a useful target for the analgesic treatment of postherpetic neuralgia.
比较了阿片类激动剂的镇痛作用以及感染疱疹病毒诱导的疱疹性疼痛小鼠和疱疹后神经痛小鼠中μ-阿片受体和κ-阿片受体的表达。吗啡对疱疹性疼痛的抑制作用比对疱疹后神经痛更有效。鞘内注射降低了吗啡对疱疹后神经痛的镇痛作用，但脑室内注射则没有。κ-阿片受体激动剂纳呋拉啡对疱疹性疼痛和疱疹后神经痛的抑制程度相似。在疼痛的疱疹后阶段而非疱疹阶段，腰段背角中μ-阿片受体样免疫反应性显著降低。在背根神经节中，疱疹后神经痛小鼠的μ-阿片受体mRNA表达显著降低，而κ-阿片受体mRNA水平未改变。这些结果表明，初级感觉神经元中μ-阿片受体的特异性下调是吗啡对疱疹后神经痛镇痛作用减弱的原因。κ-阿片受体可能是疱疹后神经痛镇痛治疗的一个有用靶点。
