title: Descending antinociception induced by secondary somatosensory cortex stimulation in experimental neuropathy: role of the medullospinal serotonergic pathway.
abstract: Stimulation of the secondary somatosensory cortex (S2) has attenuated pain in humans and inflammatory nociception in animals. Here we studied S2 stimulation-induced antinociception and its underlying mechanisms in an experimental animal model of neuropathy induced by spinal nerve ligation (SNL). Effect of S2 stimulation on heat-evoked limb withdrawal latency was assessed in lightly anesthetized rats that were divided into three groups based on prior surgery and monofilament testing before induction of anesthesia:1) sham-operated group and2) hypersensitive and3) nonhypersensitive (mechanically) SNL groups. In a group of hypersensitive SNL animals, a 5-HT1Areceptor agonist was microinjected into the rostroventromedial medulla (RVM) to assess whether autoinhibition of serotonergic cell bodies blocks antinociception. Additionally, effect of S2 stimulation on pronociceptive ON-cells and antinociceptive OFF-cells in the RVM or nociceptive spinal wide dynamic range (WDR) neurons were assessed in anesthetized hypersensitive SNL animals. S2 stimulation induced antinociception in hypersensitive but not in nonhypersensitive SNL or sham-operated animals. Antinociception was prevented by a 5-HT1Areceptor agonist in the RVM. Antinociception was associated with decreased duration of heat-evoked response in RVM ON-cells. In spinal WDR neurons, heat-evoked discharge was delayed by S2 stimulation, and this antinociceptive effect was prevented by blocking spinal 5-HT1Areceptors. The results indicate that S2 stimulation suppresses nociception in SNL animals if SNL is associated with tactile allodynia-like hypersensitivity. In hypersensitive SNL animals, S2 stimulation induces antinociception mediated by medullospinal serotonergic pathways acting on the spinal 5-HT1Areceptor, and partly through reduction of the RVM ON-cell discharge.NEW & NOTEWORTHYStimulation of S2 cortex, but not that of an adjacent cortical area, induced descending heat antinociception in rats with the spinal nerve ligation-induced model of neuropathy. Antinociception was bilateral, and it involved suppression of pronociceptive medullary cells and activation of serotonergic pathways that act on the spinal 5-HT1Areceptor. S2 stimulation failed to induce descending antinociceptive effect in sham-operated controls or in nerve-ligated animals that had not developed mechanical hypersensitivity.
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
authors.forename: Boriss
authors.initials: B
authors.lastname: Sagalajev
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
authors.forename: Hanna
authors.initials: H
authors.lastname: Viisanen
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
authors.forename: Hong
authors.initials: H
authors.lastname: Wei
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Helsinki, Helsinki, Finland antti.pertovaara@helsinki.fi.
authors.forename: Antti
authors.identifier: 0000-0002-8590-7220
authors.initials: A
authors.lastname: Pertovaara
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000200:Action Potentials / Q000502:physiology; D000818:Animals; D004195:Disease Models, Animal; D004558:Electric Stimulation; D007839:Functional Laterality; D006930:Hyperalgesia / Q000503:physiopathology; D008526:Medulla Oblongata / Q000166:cytology; D009437:Neuralgia / Q000628:therapy*; D009474:Neurons / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology*; D013003:Somatosensory Cortex / Q000502:physiology*; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism*; D013127:Spinal Nerves
chemical_list: D017366:Serotonin Receptor Agonists; D044282:Receptor, Serotonin, 5-HT1A; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin
keywords: 5-HT1A receptor; SII cortex; descending inhibition; neuropathic hypersensitivity; rostroventromedial medulla; spinal wide dynamic range neuron