PMID- 34391797 OWN - NLM STAT- MEDLINE DCOM- 20220208 LR - 20220208 IS - 1872-7549 (Electronic) IS - 0166-4328 (Linking) VI - 415 DP - 2021 Oct 11 TI - The primary motor cortex electrical and chemical stimulation attenuates the chronic neuropathic pain by activation of the periaqueductal grey matter: The role of NMDA receptors. PG - 113522 LID - S0166-4328(21)00410-1 [pii] LID - 10.1016/j.bbr.2021.113522 [doi] AB - BACKGROUND: Motor cortex stimulation (MCS) is proper as a non-pharmacological therapy for patients with chronic and neuropathic pain (NP). AIMS: This work aims to investigate if the MCS in the primary motor cortex (M(1)) produces analgesia and how the MCS could interfere in the MCS-induced analgesia. Also, to elucidate if the persistent activation of N-methyl-d-aspartic acid receptor (NMDAr) in the periaqueductal grey matter (PAG) can contribute to central sensitisation of the NP. METHODS: Male Wistar rats were submitted to the von Frey test to evaluate the mechanical allodynia after 21 days of chronic constriction injury (CCI) of the sciatic nerve. The MCS was performed with low-frequency (20 muA, 100 Hz) currents during 15 s by a deep brain stimulation (DBS) device. Moreover, the effect of M(1)-treatment with an NMDAr agonist (at 2, 4, and 8 nmol) was investigated in CCI rats. The PAG dorsomedial column (dmPAG) was pretreated with the NMDAr antagonist LY 235959 (at 8 nmol), followed by MCS. RESULTS: The MCS decreased the mechanical allodynia in rats with chronic NP. The M(1)-treatment with an NMDA agonist at 2 and 8 nmol reduced the mechanical allodynia in CCI rats. In addition, dmPAG-pretreatment with LY 235959 at 8 nmol attenuated the mechanical allodynia evoked by MCS. CONCLUSION: The M(1) cortex glutamatergic system is involved in the modulation of chronic NP. The analgesic effect of MCS may depend on glutamate signaling recruitting NMDAr located on PAG neurons in rodents with chronic NP. CI - Copyright (c) 2021. Published by Elsevier B.V. FAU - Negrini-Ferrari, Sylmara Esther AU - Negrini-Ferrari SE AD - Laboratory of Neurosciences of Pain & Emotions and Multi-User Centre of Neuroelectrophysiology, Department of Surgery and Anatomy, Ribeirao Preto Medical School of the University of Sao Paulo, Av. Bandeirantes, 3900, Ribeirao Preto, Sao Paulo, Brazil; Laboratory of Neuroanatomy and Neuropsychobiology, Department of Pharmacology, Ribeirao Preto Medical School of the University of Sao Paulo (FMRP-USP), Av. Bandeirantes, 3900, Ribeirao Preto, Sao Paulo, 14049-900, Brazil. FAU - Medeiros, Priscila AU - Medeiros P AD - Laboratory of Neurosciences of Pain & Emotions and Multi-User Centre of Neuroelectrophysiology, Department of Surgery and Anatomy, Ribeirao Preto Medical School of the University of Sao Paulo, Av. Bandeirantes, 3900, Ribeirao Preto, Sao Paulo, Brazil; Laboratory of Neuroanatomy and Neuropsychobiology, Department of Pharmacology, Ribeirao Preto Medical School of the University of Sao Paulo (FMRP-USP), Av. Bandeirantes, 3900, Ribeirao Preto, Sao Paulo, 14049-900, Brazil. FAU - Malvestio, Rafael Braghetto AU - Malvestio RB AD - Laboratory of Neurosciences of Pain & Emotions and Multi-User Centre of Neuroelectrophysiology, Department of Surgery and Anatomy, Ribeirao Preto Medical School of the University of Sao Paulo, Av. Bandeirantes, 3900, Ribeirao Preto, Sao Paulo, Brazil; Laboratory of Neuroanatomy and Neuropsychobiology, Department of Pharmacology, Ribeirao Preto Medical School of the University of Sao Paulo (FMRP-USP), Av. Bandeirantes, 3900, Ribeirao Preto, Sao Paulo, 14049-900, Brazil. FAU - de Oliveira Silva, Mariana AU - de Oliveira Silva M AD - Laboratory of Neurosciences of Pain & Emotions and Multi-User Centre of Neuroelectrophysiology, Department of Surgery and Anatomy, Ribeirao Preto Medical School of the University of Sao Paulo, Av. Bandeirantes, 3900, Ribeirao Preto, Sao Paulo, Brazil; Laboratory of Neuroanatomy and Neuropsychobiology, Department of Pharmacology, Ribeirao Preto Medical School of the University of Sao Paulo (FMRP-USP), Av. Bandeirantes, 3900, Ribeirao Preto, Sao Paulo, 14049-900, Brazil. FAU - Medeiros, Ana Carolina AU - Medeiros AC AD - Laboratory of Neurosciences of Pain & Emotions and Multi-User Centre of Neuroelectrophysiology, Department of Surgery and Anatomy, Ribeirao Preto Medical School of the University of Sao Paulo, Av. Bandeirantes, 3900, Ribeirao Preto, Sao Paulo, Brazil; Laboratory of Neuroanatomy and Neuropsychobiology, Department of Pharmacology, Ribeirao Preto Medical School of the University of Sao Paulo (FMRP-USP), Av. Bandeirantes, 3900, Ribeirao Preto, Sao Paulo, 14049-900, Brazil. FAU - Coimbra, Norberto Cysne AU - Coimbra NC AD - Laboratory of Neurosciences of Pain & Emotions and Multi-User Centre of Neuroelectrophysiology, Department of Surgery and Anatomy, Ribeirao Preto Medical School of the University of Sao Paulo, Av. Bandeirantes, 3900, Ribeirao Preto, Sao Paulo, Brazil; Laboratory of Neuroanatomy and Neuropsychobiology, Department of Pharmacology, Ribeirao Preto Medical School of the University of Sao Paulo (FMRP-USP), Av. Bandeirantes, 3900, Ribeirao Preto, Sao Paulo, 14049-900, Brazil; Behavioural Neurosciences Institute (INeC), Av. do Cafe, 2450, Ribeirao Preto, Sao Paulo, 14050-220, Brazil. FAU - Machado, Helio Rubens AU - Machado HR AD - Laboratory of Neurosciences of Pain & Emotions and Multi-User Centre of Neuroelectrophysiology, Department of Surgery and Anatomy, Ribeirao Preto Medical School of the University of Sao Paulo, Av. Bandeirantes, 3900, Ribeirao Preto, Sao Paulo, Brazil; Brain Protection Laboratory in Childhood, Department of Surgery and Anatomy, Ribeirao Preto Medical School of the University of Sao Paulo, Avenida Bandeirantes, 3900, Ribeirao Preto, 14049-900, Sao Paulo, Brazil. FAU - de Freitas, Renato Leonardo AU - de Freitas RL AD - Laboratory of Neurosciences of Pain & Emotions and Multi-User Centre of Neuroelectrophysiology, Department of Surgery and Anatomy, Ribeirao Preto Medical School of the University of Sao Paulo, Av. Bandeirantes, 3900, Ribeirao Preto, Sao Paulo, Brazil; Laboratory of Neuroanatomy and Neuropsychobiology, Department of Pharmacology, Ribeirao Preto Medical School of the University of Sao Paulo (FMRP-USP), Av. Bandeirantes, 3900, Ribeirao Preto, Sao Paulo, 14049-900, Brazil; Biomedical Sciences Institute, Federal University of Alfenas (UNIFAL-MG), Str. Gabriel Monteiro da Silva, 700, Alfenas, 37130-000, Minas Gerais, Brazil; Behavioural Neurosciences Institute (INeC), Av. do Cafe, 2450, Ribeirao Preto, Sao Paulo, 14050-220, Brazil. Electronic address: rlfreitas@alumni.usp.br. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210812 PL - Netherlands TA - Behav Brain Res JT - Behavioural brain research JID - 8004872 RN - 0 (Excitatory Amino Acid Agonists) RN - 0 (Excitatory Amino Acid Antagonists) RN - 0 (Isoquinolines) RN - 0 (Receptors, N-Methyl-D-Aspartate) RN - AR2BHC0C6P (LY 235959) SB - IM MH - Analgesia MH - Animals MH - Chronic Pain/*therapy MH - *Deep Brain Stimulation MH - Disease Models, Animal MH - Excitatory Amino Acid Agonists/*pharmacology MH - Excitatory Amino Acid Antagonists/*pharmacology MH - Isoquinolines/pharmacology MH - Male MH - Motor Cortex/*drug effects MH - Neuralgia/*therapy MH - Periaqueductal Gray/*drug effects MH - Rats MH - Rats, Wistar MH - Receptors, N-Methyl-D-Aspartate/agonists/antagonists & inhibitors/*physiology OTO - NOTNLM OT - Analgesia OT - Chronic constriction injury OT - Chronic neuropathic pain OT - Mechanical allodynia OT - Motor cortex stimulation OT - NMDA glutamatergic receptors OT - Periaqueductal grey matter OT - Primary motor cortex EDAT- 2021/08/16 06:00 MHDA- 2022/02/09 06:00 CRDT- 2021/08/15 20:37 PHST- 2020/05/18 00:00 [received] PHST- 2021/07/31 00:00 [revised] PHST- 2021/08/09 00:00 [accepted] PHST- 2021/08/16 06:00 [pubmed] PHST- 2022/02/09 06:00 [medline] PHST- 2021/08/15 20:37 [entrez] AID - S0166-4328(21)00410-1 [pii] AID - 10.1016/j.bbr.2021.113522 [doi] PST - ppublish SO - Behav Brain Res. 2021 Oct 11;415:113522. doi: 10.1016/j.bbr.2021.113522. Epub 2021 Aug 12.