Neurochemical effects of motor cortex stimulation in the periaqueductal gray during neuropathic pain

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dc.contributorLab. Bioquímicapt_BR
dc.contributor.authorAndrade, Emerson Magno dept_BR
dc.contributor.authorMartinez, Raquel C. R.pt_BR
dc.contributor.authorPagano, Rosana L.pt_BR
dc.contributor.authorLopes, Patricia S. S.pt_BR
dc.contributor.authorAuada, Aline Vivian Vattipt_BR
dc.contributor.authorGouveia, Flavia V.pt_BR
dc.contributor.authorAntunes, Geiza F.pt_BR
dc.contributor.authorAssis, Danielle V.pt_BR
dc.contributor.authorLebrun, Ivopt_BR
dc.contributor.authorFonoff, Erich T.pt_BR
dc.identifier.citationAndrade EM, Martinez RC.R., Pagano RL., Lopes PS.S., Auada AVV, Gouveia FV., et al. Neurochemical effects of motor cortex stimulation in the periaqueductal gray during neuropathic pain. J. Neurosurg.. 2020 Jan;132:239-251. doi:10.3171/2018.7.JNS173239.pt_BR
dc.description.abstractOBJECTIVE Motor cortex stimulation (MCS) is a neurosurgical technique used to treat patients with refractory neuropathic pain syndromes. MCS activates the periaqueductal gray (PAG) matter, which is one of the major centers of the descending pain inhibitory system. However, the neurochemical mechanisms in the PAG that underlie the analgesic effect of MCS have not yet been described. The main goal of this study was to investigate the neurochemical mechanisms involved in the analgesic effect induced by MCS in neuropathic pain. Specifically, we investigated the release of g-aminobutyric acid (GABA), glycine, and glutamate in the PAG and performed pharmacological antagonism experiments to validate of our findings. METHODS Male Wistar rats with surgically induced chronic constriction of the sciatic nerve, along with sham-operated rats and naive rats, were implanted with both unilateral transdural electrodes in the motor cortex and a microdialysis guide cannula in the PAG and subjected to MCS. The MCS was delivered in single 15-minute sessions. Neurotransmitter release was evaluated in the PAG before, during, and after MCS. Quantification of the neurotransmitters GABA, glycine, and glutamate was performed using a high-performance liquid chromatography system. The mechanical nociceptive threshold was evaluated initially, on the 14th day following the surgery, and during the MCS. In another group of neuropathic rats, once the analgesic effect after MCS was confirmed by the mechanical nociceptive test, rats were microinjected with saline or a glycine antagonist (strychnine), a GABA antagonist (bicuculline), or a combination of glycine and GABA antagonists (strychnine+bicuculline) and reevaluated for the mechanical nociceptive threshold during MCS. RESULTS MCS reversed the hyperalgesia induced by peripheral neuropathy in the rats with chronic sciatic nerve constriction and induced a significant increase in the glycine and GABA levels in the PAG in comparison with the naive and sham-treated rats. The glutamate levels remained stable under all conditions. The antagonism of glycine, GABA, and the combination of glycine and GABA reversed the MCS-induced analgesia. CONCLUSIONS These results suggest that the neurotransmitters glycine and GABA released in the PAG may be involved in the analgesia induced by cortical stimulation in animals with neuropathic pain. Further investigation of the mechanisms involved in MCS-induced analgesia may contribute to clinical improvements for the treatment of persistent neuropathic pain syndromespt_BR
dc.description.sponsorship(FAPESP) Fundação de Amparo à Pesquisa do Estado de São Paulopt_BR
dc.relation.ispartofJournal of Neurosurgerypt_BR
dc.titleNeurochemical effects of motor cortex stimulation in the periaqueductal gray during neuropathic painpt_BR
dc.contributor.external(USP) Universidade de São Paulopt_BR
dc.contributor.externalHospital Sírio Libanêspt_BR
dc.subject.keywordmotor cortex stimulationpt_BR
dc.subject.keywordneuropathic painpt_BR
dc.subject.keywordperiaqueductal graypt_BR
dc.subject.keywordperipheral nerve diseasept_BR
dc.relation.ispartofabbreviatedJ Neurosurgpt_BR
dc.identifier.citationabntv. 132, p. 239-251, jan. 2020pt_BR
dc.identifier.citationvancouver2020 Jan;132:239-251pt_BR
dc.contributor.butantanLebrun, Ivo|:Pesquisador:Docente Permanente PPGTOX|:Lab. Bioquímica|:pt_BR
dc.contributor.butantanAuada, Aline Vivian Vatti|:Aluno|:Lab. Bioquímica|:pt_BR
dc.sponsorship.butantan(FAPESP) Fundação de Amparo à Pesquisa do Estado de São Paulo¦¦11/08575-7pt_BR
dc.sponsorship.butantan(FAPESP) Fundação de Amparo à Pesquisa do Estado de São Paulo¦¦15/26079-8pt_BR
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