Effect of electrical and chemical (activation versus inactivation) stimulation of the infralimbic division of the medial prefrontal cortex in rats with chronic neuropathic pain

• Published in: Experimental brain research 2023-12, Vol.241 (11-12), p.2591-2604
• Main Authors: Moura-Pacheco, Thais Lohanny, Martins-Pereira, Renata Cristina, Medeiros, Priscila, Sbragia, Lourenço, Ramos Andrade Leite-Panissi, Christie, Machado, Hélio Rubens, Coimbra, Norberto Cysne, de Freitas, Renato Leonardo
• Format: Article
• Language: English
• Subjects: Agonists; Aspartic acid; Biomedical and Life Sciences; Biomedicine; Brain research; Care and treatment; Chronic pain; Cobalt; Cobalt chloride; Cognitive ability; Complications and side effects; Cortex (somatosensory); Deep brain stimulation; Glutamic acid receptors; Glutamic acid receptors (ionotropic); Laboratory animals; Methyl aspartate; N-Methyl-D-aspartic acid receptors; Neocortex; Neuralgia; Neurology; Neurosciences; Pain; Pain perception; Patient outcomes; Prefrontal cortex; Research Article; Sciatic nerve; Surgery
• ISSN: 0014-4819; 1432-1106
• DOI: 10.1007/s00221-023-06657-y

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 (CoCl 2 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. CoCl 2 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.