BackgroundMany studies have shown the antinociceptive effects of cannabinoid (CB) agonists in different models of pain. Herein, we have investigated their relevance in neuropathic pain induced by brachial plexus avulsion (BPA) in mice.Methodology/Principal FindingsMice underwent BPA or sham surgery. The mRNA levels and protein expression of CB1 and CB2 receptors were assessed by RT-PCR and immunohistochemistry, respectively. The activation of glial cells, MAP kinases and transcription factors were evaluated by immunohistochemistry. The antinociceptive properties induced by cannabinoid agonists were assessed on the 5th and 30th days after surgery. We observed a marked increase in CB1 and CB2 receptor mRNA and protein expression in the spinal cord and dorsal root ganglion, either at the 5th or 30th day after surgery. BPA also induced a marked activation of p38 and JNK MAP kinases (on the 30th day), glial cells, such as microglia and astrocytes, and the transcription factors CREB and NF-κB (at the 5th and 30th days) in the spinal cord. Systemic treatment with cannabinoid agonists reduced mechanical allodynia on both the 5th and 30th days after surgery, but the greatest results were observed by using central routes of administration, especially at the 30th day. Treatment with WIN 55,212-2 prevented the activation of both glial cells and MAP kinases, associated with an enhancement of CREB and NF-κB activation.Conclusions/SignificanceOur results indicate a relevant role for cannabinoid agonists in BPA, reinforcing their potential therapeutic relevance for the management of chronic pain states.
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