Cellular mechanisms of cannabinoid analgesia

阿片类药物是用于治疗中重度疼痛的最重要的药物，然而耐受性的形成限制了它们的有效性。此外，临床上重要的疼痛状态，特别是神经病理性疼痛，对阿片类药物治疗不敏感。人类和动物研究表明，植物大麻的活性成分THC和一些合成大麻素也具有止痛或缓解疼痛的特性。特别令人感兴趣的是，发现大麻类物质增强了阿片类药物的止痛作用。已知有几个大脑区域在阿片类药物和大麻类药物的止痛作用中发挥关键作用。在以前的研究中，我已经确定了阿片类药物在单个脑细胞中产生止痛作用的细胞和分子机制。然而，大麻素在脑内诱导镇痛的细胞机制却知之甚少。此外，大麻素和阿片类药物在神经病理性疼痛状态下的细胞作用尚不清楚。这项拟议的研究将确定大麻素和阿片类药物在正常和神经病理性疼痛状态下单个脑神经元的止痛作用的细胞和分子机制。这些技术有可能确定大麻类药物和其他具有增强疗效和减少副作用的药物之间的抗伤害性组合。

Opioids are the most important drugs used to treat moderate to severe pain, however the development of tolerance limits their usefulness. In addition, clinically important pain states, particularly neuropathic pain, are insensitive to opioid treatment. Human and animal studies indicate that the active ingredient of the plant cannabis sativa, THC, and a number of synthetic cannabinoids also have analgesic, or pain relieving properties. Of particular interest is the finding that cannabinoids enhance the analgesic actions of opioids. Several brain regions are known to play a pivotal role in the analgesic actions of both opioids and cannabinoids. In previous studies I have identified the cellular and molecular mechanisms by which opioid drugs produce their analgesic effects in single brain cells. However, the cellular mechanisms underlying cannabinoid induced analgesia within the brain are poorly understood. In addition, the cellular actions of cannabinoids and opioids in neuropathic pain states are unknown. The proposed study will determine the cellular and molecular mechanisms underlying the analgesic actions of cannabinoids and opioids in single brain neurons in normal and neuropathic pain states. These techniques have the potential to identify antinociceptive combinations between cannabinoids and other agents with enhanced efficacy and reduced side effects.