title: The rostroventromedial medulla is engaged in the effects of spinal cord stimulation in a rodent model of neuropathic pain.
abstract: The neurobiological mechanisms underlying the suppression of neuropathic pain by spinal cord stimulation (SCS) are still incompletely known. The present study aims at exploring whether the descending pain control system in the rostroventromedial medulla (RVM) exerts a role in the attenuation of neuropathic pain by SCS. Experiments were performed in the rat spared nerve injury (SNI) pain model. The effects of SCS on neuronal activity of pronociceptive ON-like, antinociceptive OFF-like, and neutral cells, including 5-HT-like cells, in the RVM were analyzed in SCS responding and SCS non-responding SNI animals as well as in naïve controls. Decreased spontaneous activities in OFF-like cells and increased spontaneous activities in ON-like cells were observed in SNI animals, whereas the spontaneous activities of 5-HT-like and neutral cells were unchanged. SCS produced a prominent increase in the discharge of OFF- and 5-HT-like cells in SCS responding, but not in non-responding SNI animals or controls. Discharge rates of ON-like and neutral cell were not affected by SCS. In awake SNI animals, microinjection of a GABAA receptor agonist, muscimol, into the RVM significantly attenuated the antihypersensitivity effect induced by SCS while a non-selective opioid receptor antagonist, naltrexone, was ineffective. It is concluded that SCS may shift the reciprocal inhibitory and facilitatory pain modulation balance controlled by the RVM in favor of inhibition. This increase in the descending antinociceptive effect operates in concert with segmental spinal mechanisms in producing pain relief.
authors.affiliation: Department of Clinical Neuroscience, Section of Neurosurgery, Karolinska Institutet, SE 171 76 Stockholm, Sweden. zhiyang.song@ki.se
authors.forename: Z
authors.initials: Z
authors.lastname: Song
authors.forename: O B
authors.initials: OB
authors.lastname: Ansah
authors.forename: B A
authors.initials: BA
authors.lastname: Meyerson
authors.forename: A
authors.initials: A
authors.lastname: Pertovaara
authors.forename: B
authors.initials: B
authors.lastname: Linderoth
mesh_terms: D000818:Animals; D008297:Male; D008526:Medulla Oblongata / Q000502:physiology*; D009434:Neural Pathways / Q000502:physiology; D009437:Neuralgia / Q000503:physiopathology / Q000628:therapy*; D059408:Pain Management / Q000379:methods*; D010147:Pain Measurement / Q000379:methods*; D051381:Rats; D017208:Rats, Wistar; D062187:Spinal Cord Stimulation / Q000379:methods*; D016896:Treatment Outcome
keywords: 5-HT; ANOVA; AUC; DLF; MT; RVM; SCS; SD; SNI; WT; analysis of variance; area under curve; dorsolateral funiculus; motor threshold; neuropathic pain; rostroventromedial medulla; spared nerve injury; spinal cord stimulation; standard deviation; withdrawal thresholds