CB1-cannabinoid-, TRPV1-vanilloid- and NMDA-glutamatergic-receptor-signalling systems interact in the prelimbic cerebral cortex to control neuropathic pain symptoms

Author(s)

Medeiros, Priscila ^{[1, 2, 3]} ; Oliveira-Silva, Mariana ^{[1, 2]} ; Negrini-Ferrari, Sylmara Esther ^{[1, 2]} ; Medeiros, Ana Carolina ^{[1, 2, 3]} ; Elias-Filho, Daoud Hibraim ^[3] ; Coimbra, Norberto Cysne ^{[4, 1, 2, 3]} ; de Freitas, Renato Leonardo ^{[4, 1, 2, 3, 5]}

Affiliation

^[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Surg & Anat, Lab Neurosci Pain & Emot, BR-14049900 Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Surg & Anat, Multiuser Ctr Neuroelectrophysiol, BR-14049900 Ribeirao Preto, SP - Brazil

^[3] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pharmacol, Lab Neuroanat & Neuropsychobiol, FMRP USP, Av Bandeirantes 3900, BR-14049900 Ribeirao Preto, SP - Brazil

^[4] Behav Neurosci Inst INeC, Av Cafe 2450, BR-14050220 Ribeirao Preto, SP - Brazil

^[5] Univ Fed Alfenas, Biomed Sci Inst, UNIFAL MG, Str Gabriel Monteiro da Silva 700, BR-37130000 Alfenas, MG - Brazil

• Document type: Journal article
• Source: Brain Research Bulletin; v. 165, p. 118-128, DEC 2020.
• Web of Science Citations: 0

Abstract

Neuropathic pain (NP) is a challenge due to our limited understanding of the mechanisms that initiate and maintain chronic pain. The prelimbic division (PrL) of the medial prefrontal cortex (mPFC) is an important area of the emotional and cognitive components of pain and pharmacological systems can interact into the neocortex to elaborate the chronic pain. This work aimed to investigate the pharmacological cross-talk between synaptic neurotransmission, neuroanatomical approaches and NP conditions. A bidirectional neural tract tracer, the 3000-molecular-weight biodextran (BDA) was microinjected into the PrL cortex. The mechanical withdrawal threshold (MWT) was recorded by a von Frey test, and the effect of prelimbic cortex CB1, NMDA, and TRPV1 receptor modulation was evaluated 21 days after chronic constriction injury (CCI) of the sciatic nerve in male Wistar rats. Microinjection of a bidirectional neurotracer in the PrL cortex showed connections with the lateral division of the mediodorsal thalamic nucleus (MDL), central division of the mediodorsal thalamic nucleus (MDC), centrolateral thalamic nucleus (CL), ventromedial thalamic nucleus (VM), and the paracentral thalamic nucleus (PC). In detail, AM251, a CB1 receptor antagonist (at 50, 100 and 200 pmol) microinjections intra-PrL cortex decreased the MWT. Administrations of 6-iodonordihydrocapsaicin (6-I-CPS), a transient receptor potential vanilloid type 1 (TRPV1) antagonist, at 3 nmol and the endocannabinoid anandamide (AEA) at 50 and 100 pmol increased the MWT. AEA at 200 pmol injected in the PrL cortex decreased the MWT, and this hyperalgesic effect was blocked by 6-I-CPS at 3 nmol. The AEA (at 100 pmol) anti-allodynic effect was attenuated by AM251 (at 5 pmol). The TRPV1 selective agonist N-oleoyldopamine (OLDA) at 10 mu M decreased the MWT. The blockade of the NMDA receptor with LY235959 (at 8 nmol) and 6-I-CPS (at 3 nmol) reversed the OLDA (at 10 mu M) hyperalgesic effect. These findings showed that the PrL cortex sends pathways to thalamic nuclei that can mediate the nociception. We also suggest that the PrL cortex is involved in the potentiation and maintenance of mechanical allodynia by NMDA and TRPV1 receptor activation and that attenuation of this allodynia depends on CB1 receptor activation during NP. (AU)

• FAPESP's process: 17/13560-5 - Effect of deep brain stimulation and cannabidiol treatment in the subthalamic nucleus on the motors and non-Motors symptoms in the experimental model of Parkinson Disease
• Grantee: Priscila Medeiros de Freitas
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 09/17258-5 - Study of the involvement of nitrergic system and of glutamatergic and cannabinoid-mediated neurotransmission from the medial prefrontal cortex in the analgesia induced by elaborated escape reactions evoked by GABAergic blockade in the medial hypothalamus
• Grantee: Renato Leonardo de Freitas
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 12/25167-2 - Role of glutamatergic, endocannabinoid and endovaniloid systems of medial pre-frontal cortex in neurophatic pain model: Investigation of panic and chronic pain comorbidity
• Grantee: Priscila Medeiros de Freitas
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 14/11869-0 - Multi-use equipment approved in grant 2013/12916-0: deep brain stimulation (DBS) (Thomas mini matrix system - Thomas recording GmbH® - Winchester Strasse - Giessen - Germany)
• Grantee: Renato Leonardo de Freitas
• Support Opportunities: Multi-user Equipment Program
• FAPESP's process: 14/07902-2 - Role of endocannabinoid, glutamatergic and endovanilloid systems of medial prefrontal cortex in neuropathic pain model and investigation of neurological disorders and chronic pain comorbidity
• Grantee: Renato Leonardo de Freitas
• Support Opportunities: Scholarships in Brazil - Young Researchers
• FAPESP's process: 13/12916-0 - Role of endocannabinoid, glutamatergic and endovanilloid systems of medial prefrontal cortex in neuropathic pain model and investigation of neurological disorders and chronic pain comorbidity
• Grantee: Renato Leonardo de Freitas
• Support Opportunities: Research Grants - Young Investigators Grants