title: Antinociception by motor cortex stimulation in the neuropathic rat: does the locus coeruleus play a role?
abstract: We studied whether stimulation of the primary motor cortex (M1) attenuates pain-related spinal withdrawal responses of neuropathic and healthy control rats, and whether the descending antinociceptive effect is relayed through the noradrenergic locus coeruleus (LC). The assessments of the noxious heat-evoked limb withdrawals reflecting spinal nociception and recordings of single LC units were performed in spinal nerve-ligated neuropathic and sham-operated control rats under light pentobarbital anesthesia. Electric stimulation of M1 produced equally strong spinal antinociception in neuropathic and control rats. Following microinjection into M1, a group I metabotropic glutamate receptor agonist (DHPG; 10 nmol) and a high (25 nmol) but not low (2.5 nmol) dose of glutamate slightly increased on-going discharge rates of LC neurons in neuropathic but not in control animals. Influence of electric stimulation of M1 on LC neurons was studied only in the neuropathic group, in which discharge rates of LC neurons were increased by electric M1 stimulation. Lidocaine block of the LC or block of descending noradrenergic influence by intrathecal administration of a alpha(2)-adrenoceptor antagonist failed to produce a significant attenuation of the spinal antinociceptive effect induced by electric M1 stimulation in the neuropathic or the sham group. The results indicate that stimulation of the rat M1 induces spinal antinociception in neuropathic as well as control conditions. While M1 stimulation may activate the LC, particularly in the neuropathic group, the contribution of coeruleospinal noradrenergic pathways may not be critical for the spinal antinociceptive effect induced by M1 stimulation.
authors.affiliation: Biomedicum Helsinki, Institute of Biomedicine/Physiology, POB 63, University of Helsinki, 00014, Helsinki, Finland.
authors.forename: Hanna
authors.initials: H
authors.lastname: Viisanen
authors.forename: Antti
authors.initials: A
authors.lastname: Pertovaara
mesh_terms: D058669:Adrenergic alpha-2 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000779:Anesthetics, Local / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D017776:Autonomic Pathways / Q000502:physiology; D004599:Electric Stimulation Therapy / Q000379:methods*; D004594:Electrophysiology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D006358:Hot Temperature; D007278:Injections, Spinal; D008012:Lidocaine / Q000008:administration & dosage / Q000494:pharmacology; D008026:Ligation; D008125:Locus Coeruleus / Q000503:physiopathology*; D008297:Male; D008845:Microinjections; D009044:Motor Cortex / Q000502:physiology*; D010146:Pain / Q000503:physiopathology*; D059408:Pain Management; D010523:Peripheral Nervous System Diseases / Q000503:physiopathology* / Q000628:therapy*; D051381:Rats; D017208:Rats, Wistar; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects / Q000502:physiology; D012018:Reflex / Q000187:drug effects / Q000502:physiology; D012118:Resorcinols / Q000494:pharmacology; D013116:Spinal Cord; D013127:Spinal Nerves / Q000473:pathology
chemical_list: D058669:Adrenergic alpha-2 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D000779:Anesthetics, Local; D018690:Excitatory Amino Acid Agonists; D018341:Receptors, Adrenergic, alpha-2; D012118:Resorcinols; C079215:3,5-dihydroxyphenylglycine; D008012:Lidocaine; D005998:Glycine