Spinal and pontine alpha2-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 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.
Wei
Hong
H
Biomedicum Helsinki, Institute of Biomedicine/Physiology, POB 63, 00014 University of Helsinki, Finland.
Pertovaara
Antti
A
D000317:Adrenergic alpha-Antagonists / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006358:Hot Temperature; D006930:Hyperalgesia / Q000209:etiology / Q000378:metabolism* / Q000517:prevention & control; D007093:Imidazoles / Q000494:pharmacology; D007276:Injections, Intraventricular; D007278:Injections, Spinal; D008297:Male; D008845:Microinjections; D009433:Neural Inhibition / Q000235:genetics; D010146:Pain / Q000209:etiology / Q000378:metabolism* / Q000517:prevention & control; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects; D011149:Pons / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects / Q000378:metabolism*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*; D013119:Spinal Cord Injuries / Q000150:complications / Q000378:metabolism; D013127:Spinal Nerves / Q000601:surgery; D013997:Time Factors; D014110:Touch
D000317:Adrenergic alpha-Antagonists; D007093:Imidazoles; D018341:Receptors, Adrenergic, alpha-2; C050701:atipamezole