Spinal and pontine α2-adrenoceptors have opposite effects on pain-related behavior in the neuropathic rat

Descending noradrenergic pathways contribute to feedback inhibition of pain by releasing norepinephrine in the spinal cord. Noradrenergic nuclei in the pons contain abundant α2-adrenoceptors. We assessed the contribution of pontine α2-adrenoceptors to endogenous regulation of pain in nerve-injured rats. Tactile allodynia and mechanical hyperalgesia were assessed in the injured dermatome and heat nociception in an uninjured dermatome. Atipamezole, an α2-adrenoceptor antagonist, or saline was administered systemically or microinjected into the locus coeruleus, the lateral parabrachial nucleus, the central nucleus of the amygdala, the midbrain periaqueductal gray, and/or through an intrathecal (i.t.) catheter to the spinal cord. Atipamezole administered systemically, into the amygdala or the periaqueductal gray had no significant effects on pain behavior. Atipamezole (0.3–5 μg) microinjected into the pons, the locus coeruleus or the lateral parabrachial nucleus, produced a selective and dose-related antiallodynia, which was reversed by i.t. administration of atipamezole (5 μg). I.t. administration of atipamezole alone (5 μg) produced thermal hypersensitivity in the non-neuropathic segment (tail) of nerve-injured animals. In sham-operated controls, i.t. administration of atipamezole had no effect. Suppression of heat nociception in uninjured dermatomes of nerve-injured but not the control animals following i.t. administration of atipamezole indicates that nerve injury produced a tonic activation of noradrenergic feedback inhibition acting on spinal α2-adrenoceptors. In parallel, antiallodynia induced by pontine administration of atipamezole indicates that nerve injury induces a tonic activation of pontine α2-adrenoceptors that promotes neuropathic hypersensitivity by attenuating descending inhibition. Thus, spinal and pontine α2-adrenoceptors have opposite effects on pain-related behavior in neuropathic animals.