title: Microinjection of carbachol in the lateral hypothalamus produces opposing actions on nociception mediated by alpha(1)- and alpha(2)-adrenoceptors.
abstract: Electrical stimulation of the lateral hypothalamus (LH) produces antinociception partially blocked by intrathecal alpha-adrenergic antagonists, but the mechanism underlying this effect is not clear. Evidence from immunological studies demonstrates that substance P-immunoreactive neurons in the LH project near the A7 catecholamine cell group, a group of noradrenergic neurons in the pons known to effect antinociception in the spinal cord dorsal horn. Such evidence suggests that LH neurons may activate A7 neurons to produce antinociception. To test this hypothesis, the cholinergic agonist carbachol was microinjected into the LH at doses of 63, 125 and 250 nmol and the resulting effects on tail-flick and nociceptive foot-withdrawal latencies were measured. All three doses significantly increased response latencies on both tests, with the 125-nmol dose providing the optimal effect. Intrathecal injection of the opioid antagonist naltrexone (97 nmol) partially reversed antinociception, but neither the alpha(2)-adrenoceptor antagonist yohimbine nor the alpha(1)-adrenoceptor antagonist WB4101 altered latencies. However, two sequential doses of yohimbine blocked LH-induced antinociception on both tests. In contrast, two sequential doses of WB4101 increased nociceptive responses on both the tail-flick and foot-withdrawal tests. These findings, and those of published reports, suggest that neurons in the LH activate spinally projecting methionine enkephalin neurons, as well as two populations of A7 noradrenergic neurons that exert a bidirectional effect on nociception. One of these populations increases nociception through the action of alpha(1)-adrenoceptors and the other inhibits nociception through the action of alpha(2)-adrenoceptors in the spinal cord dorsal horn.
authors.affiliation: Department of Medical-Surgical Nursing, The University of Illinois at Chicago, Chicago, IL 60612-7350, USA. jeholden@uic.edu
authors.forename: J E
authors.initials: JE
authors.lastname: Holden
authors.forename: E
authors.initials: E
authors.lastname: Naleway
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000698:Analgesia; D000818:Animals; D002217:Carbachol / Q000494:pharmacology*; D018679:Cholinergic Agonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004525:Efferent Pathways / Q000187:drug effects / Q000378:metabolism; D005260:Female; D007026:Hypothalamic Area, Lateral / Q000187:drug effects* / Q000378:metabolism; D007278:Injections, Spinal; D009619:Nociceptors / Q000187:drug effects* / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D010146:Pain / Q000378:metabolism* / Q000503:physiopathology; D010147:Pain Measurement / Q000187:drug effects; D011149:Pons / Q000187:drug effects / Q000378:metabolism; D020671:Posterior Horn Cells / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects* / Q000378:metabolism; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects* / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000187:drug effects / Q000378:metabolism; D013373:Substance P / Q000378:metabolism
chemical_list: D000317:Adrenergic alpha-Antagonists; D018679:Cholinergic Agonists; D018340:Receptors, Adrenergic, alpha-1; D018341:Receptors, Adrenergic, alpha-2; D017450:Receptors, Opioid, mu; D013373:Substance P; D002217:Carbachol; D009638:Norepinephrine