Cellular actions of cannabinoids within the spinal cord dorsal horn in a neuropathic pain state

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Morphine and other opioids are among the most important drugs used to treat moderate to severe pain. However, some clinically important chronic pain states are relatively insensitive to opioid treatment, such as neuropathic pain which is caused by injury to the nervous system. Human and animal studies indicate that the active ingredient of the plant cannabis sativa, THC, and a number of synthetic cannabis-like drugs (cannabinoids) also have analgesic, or pain relieving properties. Animal studies have shown that cannabinoids potentiate the analgesic effects of opioids. Of particular interest is the finding that cannabinoids reduce the abnormal pain symptoms associated with animal models of neuropathic pain, such as that caused by nerve injury. Several brain regions play a pivotal role in the analgesic actions of both opioids and cannabinoids. In previous studies I have identified the cellular mechanisms by which opioids and cannabinoids produce their analgesic effects in single cells within the brain. In addition, the spinal cord is the initial relay point of painful stimuli entering the central nervous system and is a major site of opioids and cannabinoid analgesic actions. However, the cellular mechanisms underlying cannabinoid and opioid actions within the spinal cord, particularly in pathways which transmit ascending pain information to the brain, are less well understood. In addition, the cellular actions of cannabinoids and opioids in neuropathic pain states are unknown. The proposed study will determine the cellular mechanisms underlying the analgesic actions of cannabinoids and opioids in single neurons identified as belonging to pain pathways within the spinal cord in normal and nerve injured animals. These techniques have the potential to identify analgesic combinations between cannabinoids, opioids and other agents with enhanced therapeutic activity and reduced side effects.