Abstract
Neuropathic pain (NP) represents a complex disorder with sensory, cognitive, and emotional symptoms. The medial prefrontal cortex (mPFC) takes critical regulatory roles and may change functionally and morphologically during chronic NP. There needs to be a complete understanding of the neurophysiological and psychopharmacological bases of the NP phenomenon. This study aimed to investigate the participation of the infralimbic division (IFL) of the mPFC in chronic NP, as well as the role of the N-methyl-D-aspartic acid receptor (NMDAr) in the elaboration of chronic NP. Male Wistar rats were submitted to the von Frey and acetone tests to assess mechanical and cold allodynia after 21 days of chronic constriction injury (CCI) of the sciatic nerve or Sham-procedure (“false operated”). Electrical neurostimulation of the IFL/mPFC was performed by low-frequency stimuli (20 μA, 100 Hz) applied for 15 s by deep brain stimulation (DBS) device 21 days after CCI. Either cobalt chloride (CoCl2 at 1.0 mM/200 nL), NMDAr agonist (at 0.25, 1.0, and 2.0 nmol/200 nL) or physiological saline (200 nL) was administered into the IFL/mPFC. CoCl2 administration in the IFL cortex did not alter either mechanical or cold allodynia. DBS stimulation of the IFL cortex decreased mechanical allodynia in CCI rats. Chemical stimulation of the IFL cortex by an NMDA agonist (at 2.0 nmol) decreased mechanical allodynia. NMDA at any dose (0.25, 1.0, and 2.0 nmol) reduced the flicking/licking duration in the cold test. These findings suggest that the IFL/mPFC and the NMDAr of the neocortex are involved in attenuating chronic NP in rats.
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The data that support the findings of this study are available from the corresponding author, R.L. de Freitas, upon reasonable request.
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Acknowledgements
Special thanks to Mr. Paulo Castilho, Ms. Ariane Santana, Mr. Daoud Hibrahim Elias Filho, and Ms. Maria Rossato for their expert technical assistance.
Funding
This research was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) (Research Grant 2013/12916-0 and Multi-user Equipment Grant 2014/11869-0) and Conselho Nacional de Pesquisa e Desenvolvimento Tecnológico (CNPq) (Grant 427397/2018-9). Neither of these funding sources had any role in the study design, collection, analysis, and interpretation of the data, report writing, or decision to submit the paper for publication. R L de Freitas was supported by FAPESP (Scientific Initiation Scholarship Grant 2001/03752-6, M.Sc. fellowship grant 2003/05256-1, post-doctoral fellowship Grant 2009/17258-5, and researcher fellowship grant 2014/07902-2) and CAPES (Sc.D. fellowship Grant 001). FAPESP also supported Priscila de Medeiros (Sc.D. fellowship Grant 2012/25167–2; post-doctoral fellowship grant 2017/13560-5). CNPq supported Priscila Medeiros (post-doctoral fellowship Grant 150806/2021-3). CAPES supported Renata C. Martins Pereira (M.Sc. fellowship Grant 88887.474986/2020-00). Neither of these funding sources had any role in the study design, collection, analysis, and interpretation of the data, report writing, or decision to submit the paper for publication.
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TLM-P, PM and RCMP performed the experiments, analyzed and interpreted the data, and designed the figures; TLM-P, RCMP and RLF wrote the manuscript. LS, CRL-P, HRM and NCC analyzed and interpreted the data and revised the final manuscript. Renato Leonardo de Freitas designed the experiments, analyzed and interpreted the data, wrote the manuscript, and approved the final manuscript. All authors have approved the final version of the manuscript.
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Moura-Pacheco, T.L., Martins-Pereira, R.C., Medeiros, P. et al. Effect of electrical and chemical (activation versus inactivation) stimulation of the infralimbic division of the medial prefrontal cortex in rats with chronic neuropathic pain. Exp Brain Res 241, 2591–2604 (2023). https://doi.org/10.1007/s00221-023-06657-y
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DOI: https://doi.org/10.1007/s00221-023-06657-y