Peripheral versus central mechanisms of the cannabinoid type 2 receptor agonist AM1710 in a mouse model of neuropathic pain

Either i.p. or i.t. AM1710 reversed CCI ‐induced mechanical allodynia in CB1R (−/−), (+/−), (+/+) mice similar to sham control threshold levels. The absence of the CB1R following CCI‐induced neuropathy revealed greater significant increases in IL‐10 immunoreactivity (IR) in the dorsal root ganglia (DRG) and the dorsal horn of the spinal cord in (−/−) and (+/−) mice that was further elevated following i.t. and i.p. AM1710. The absence of CB1R may allow for enhanced tissue/axon damage‐associated signaling to the DRG and spinal cord, resulting in endogenous compensatory increases in IL‐10 expression. AbstractThe CB2R agonist AM1710, examined in animal models of peripheral neuropathy, is effective in controlling aberrant light touch sensitivity, referred to as mechanical allodynia. However, nonspecific binding of AM1710 to CB1R, either peripherally or centrally, could be partially responsible for the analgesic effects of AM1710. Thus, we sought to determine in mice whether spinal (intrathecal; i.t.) or peripheral AM1710 administration could lead to anti ‐allodynia by reducing the protein expression of spinal and dorsal root ganglia (DRG) proinflammatory cytokines and elevating the anti‐inflammatory cytokine interleukin‐10 (IL‐10) in the absence of CB1R. Macrophage cell cultures were examined to characterize AM1710 ‐mediated suppression of the proinflammatory cytokine tumor necrosis factor‐alpha (TNF‐α). Either i.p. or i.t. AM1710 reversed CCI...
Source: Brain and Behavior - Category: Neurology Authors: Tags: ORIGINAL RESEARCH Source Type: research