Richardson J D, Aanonsen L, Hargreaves K M
Department of Pharmacology, University of Minnesota, Minneapolis 55455, USA.
Eur J Pharmacol. 1998 Mar 19;345(2):145-53. doi: 10.1016/s0014-2999(97)01621-x.
Cannabinoids have been widely reported to produce antinociception in models such as tail flick and hot plate. However, their role in modulating thermal hyperalgesia is unknown. The potency of some drugs, such as the opioids, increases during hyperalgesia. Thus, we evaluated whether there is a change in the effectiveness of intrathecal cannabinoids with hyperalgesia. Additionally, we evaluated whether cannabinoids could inhibit capsaicin-evoked neurosecretion from isolated rat spinal cord. Our results indicate that 1 fmol anandamide (i.t.) completely blocked carrageenan-induced thermal hyperalgesia. However, anandamide at doses as high as 100 pmol had no effect on thermal latencies in normal animals. Additionally, anandamide inhibited K+- as well as capsaicin-evoked immunoreactive calcitonin gene-related peptide release. Finally, cannabinoid receptors were identified in sensory neurons. Collectively, these results indicate that there is an increased effectiveness of modulation of thermal nociceptive thresholds by spinal cannabinoids during hyperalgesia. This antihyperalgesic effect may be the result of cannabinoid-induced inhibition of neurosecretion from certain primary afferent fibers.
大麻素在甩尾和热板等模型中产生抗伤害感受的现象已有广泛报道。然而，它们在调节热痛觉过敏中的作用尚不清楚。一些药物，如阿片类药物，在痛觉过敏期间效力会增强。因此，我们评估了鞘内注射大麻素的有效性在痛觉过敏时是否会发生变化。此外，我们评估了大麻素是否能抑制辣椒素诱发的离体大鼠脊髓神经分泌。我们的结果表明，1飞摩尔花生四烯乙醇胺（鞘内注射）可完全阻断角叉菜胶诱导的热痛觉过敏。然而，高达100皮摩尔剂量的花生四烯乙醇胺对正常动物的热潜伏期没有影响。此外，花生四烯乙醇胺可抑制钾离子以及辣椒素诱发的免疫反应性降钙素基因相关肽的释放。最后，在感觉神经元中鉴定出了大麻素受体。总体而言，这些结果表明，在痛觉过敏期间，脊髓大麻素对热伤害性感受阈值的调节有效性增加。这种抗痛觉过敏作用可能是大麻素诱导抑制某些初级传入纤维神经分泌的结果。
