• Hong Wei and Antti Pertovaara.
• Biomedicum Helsinki, Institute of Biomedicine/Physiology, POB 63, 00014 University of Helsinki, Finland.
• Eur. J. Pharmacol. 2006 Dec 3;551(1-3):41-9.

AbstractDescending noradrenergic pathways contribute to feedback inhibition of pain by releasing norepinephrine in the spinal cord. Noradrenergic nuclei in the pons contain abundant alpha(2)-adrenoceptors. We assessed the contribution of pontine alpha(2)-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 alpha(2)-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 microg) 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 microg). I.t. administration of atipamezole alone (5 microg) 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 alpha(2)-adrenoceptors. In parallel, antiallodynia induced by pontine administration of atipamezole indicates that nerve injury induces a tonic activation of pontine alpha(2)-adrenoceptors that promotes neuropathic hypersensitivity by attenuating descending inhibition. Thus, spinal and pontine alpha(2)-adrenoceptors have opposite effects on pain-related behavior in neuropathic animals.

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