Involyement Of Endocannabinoids And Glial Cells In Formalin Induced Long-lasting Inflammatory Pain

Objective:To investigate the roles of endocannabionoid and glia in continuous inflammatory pain induced by formalin through intrathecal injection of endocannabionoid2-AGMaterials and methods:Continuous inflammatory pain model was established through intraplantar injection of formalin (5%,50μ1). The distribution of CB subtypes (CB1, CB2) in glial cells (microglia and astrocyte) and neurons of spinal dorsal horn were observed through immunohistochemistry in naive and treated animals. Endocannabionoid2-AG was intrathecally injected to observe the changes of formalin-evoked nociceptive responses at acute stage (licking/biting paws and twitching reflex), and the distribution of CBl and CB2in glial cells and neurons. CB antagonists (AM281or AM630) were pre-intrathecally injected to observe the changes of formalin-evoked nociceptive responses at acute stage.Results:The results indicated that intrathecal injection of endocannabionoid2-AG inhibited the acute nocicpetive behaviors (licking/biting paws and twitching reflex). Intrathecal injection of CBl or CB2cannabinoid receptor (AM281or AM630) antagonists reversed analgesia induced by2-AG. Morphological results showed that CB1and CB2cannabinoid receptor was expression increased in lumbar dorsal horn. The expression of CBl cannabinoid receptor continuously increased following the time elapsed and was co-localized with neuron, astrocytes and microglia, the CB2cannabinoid receptor expression was not observed in blank control group but was continuously expressed by formalin injection and primarily co-localized with astrocytes and microglia.Conclusion:These results suggest that endocannabinoid2-AG signaling via CB1and CB2cannabinoid receptors plays an important role in the pain processing under continuous inflammation.