Cellular mechanisms of cannabinoid analgesia

阿片类药物是用于治疗中度至重度疼痛的最重要药物，然而耐受性的发展限制了它们的用途。此外，临床上重要的疼痛状态，特别是神经性疼痛，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，四氢大麻酚和一些合成大麻素也具有镇痛或缓解疼痛的特性。特别有趣的是发现大麻素增强阿片类药物的镇痛作用。已知几个大脑区域在阿片类药物和大麻素的镇痛作用中起关键作用。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镇痛作用的细胞和分子机制。然而，大麻素引起的脑内镇痛的细胞机制尚不清楚。此外，大麻素和阿片类药物在神经性疼痛状态下的细胞作用尚不清楚。该研究将确定大麻素和阿片类药物在正常和神经性疼痛状态下单个脑神经元中镇痛作用的细胞和分子机制。这些技术有潜力确定大麻素和其他药物之间的抗伤害性组合，增强疗效和减少副作用。

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.