Evidence for a novel functional role of cannabinoid CB ₂ receptors in the thalamus of neuropathic rats

Abstract

Cannabinoid CB ₁ receptors have analgesic effects in models of neuropathic pain, but can also produce psychoactive side-effects. A supraspinal location of CB ₂ receptors has recently been described. CB ₂ agonists are also antinociceptive, although the functional role of supraspinal CB ₂ receptors in the control of nociception is unknown. Herein, we provide evidence that CB ₂ receptors in the thalamus play a functional role in the modulation of responses of neurons in the ventral posterior nucleus (VPL) of the thalamus in neuropathic, but not sham-operated, rats. Spontaneous and mechanically evoked activity of VPL neurons was recorded with a multichannel electrode array in anaesthetized spinal nerve-ligated (SNL) rats and compared to sham-operated rats. Intra-VPL administration of the CB ₂ agonist JWH-133 (30 ng in 500 nL) significantly reduced spontaneous ( P < 0.05), non-noxious ( P < 0.001) and noxious ( P < 0.01) mechanically evoked responses of VPL neurons in SNL rats, but not in sham-operated rats. Inhibitory effects of JWH-133 on spontaneous ( P < 0.01) and noxious-evoked ( P < 0.001) responses of neurons were blocked by the CB ₂ antagonist SR144528. Local administration of SR144528 alone did not alter spontaneous or evoked responses of VPL neurons, but increased burst activity of VPL neurons in SNL rats. There were, however, no differences in levels of the endocannabinoids anandamide and 2AG in the thalamus of SNL and sham-operated rats. These data suggest that supraspinal CB ₂ receptors in the thalamus may contribute to the modulation of neuropathic pain responses.