Nevertheless, the mechanism by which this AR subtype exerts anti-hyperalgesic and anti-allodynic effects is still to be clarified, and before now, both peripheral (CD4+ T cell-mediated production of anti-inflammatory IL-10 or DRG neuronal inhibition) and central (spinal astrocyte reactivity inhibition, increased GABA release in the spinal cord, inhibition of spinal and supraspinal activation of serotonergic and noradrenergic circuits) effects have been described, with some gender-specific effects outlined in particular cases (e.g., bortezomib-induced neuropathic pain). This evidence concerns the gene CD4 and neuropathic pain.