Indomethacin attenuates mechanical allodynia during the organization but not the maintenance of the peripheral neuropathic pain induced by nervus ischiadicus chronic constriction injury

Author(s)

P. Medeiros ; I.R. dos Santos ^[2] ; A.C. Medeiros ; J.A. da Silva ^[4] ; S.H. Ferreira ^[5] ; R.L. de Freitas ; N.C. Coimbra

• Document type: Journal article
• Source: Brazilian Journal of Medical and Biological Research; v. 53, n. 5 2020-04-27.

Abstract

The neurochemical mechanisms underlying neuropathic pain (NP) are related to peripheral and central sensitization caused by the release of inflammatory mediators in the peripheral damaged tissue and ectopic discharges from the injured nerve, leading to a hyperexcitable state of spinal dorsal horn neurons. The aim of this work was to clarify the role played by cyclooxygenase (COX) in the lesioned peripheral nerve in the development and maintenance of NP by evaluating at which moment the non-steroidal anti-inflammatory drug indomethacin, a non-selective COX inhibitor, attenuated mechanical allodynia after placing one loose ligature around the nervus ischiadicus, an adaptation of Bennett and Xie's model in rodents. NP was induced in male Wistar rats by subjecting them to chronic constriction injury (CCI) of the nervus ischiadicus, placing one loose ligature around the peripheral nerve, and a sham surgery (without CCI) was used as control. Indomethacin (2 mg/kg) or vehicle was intraperitoneally and acutely administered in each group of rats and at different time windows (1, 2, 4, 7, 14, 21, and 28 days) after the CCI or sham surgical procedures, followed by von Frey's test for 30 min. The data showed that indomethacin decreased the mechanical allodynia threshold of rats on the first, second, and fourth days after CCI (P<0.05). These findings suggested that inflammatory mechanisms are involved in the induction of NP and that COX-1 and COX-2 are involved in the induction but not in the maintenance of NP. (AU)

• 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
• 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: 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: 13/08216-2 - CRID - Center for Research in Inflammatory Diseases
• Grantee: Fernando de Queiroz Cunha
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• 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: 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: 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: 11/19670-0 - Mechanisms involved in the pathophysiology of rheumatoid arthritis, pain and sepsis
• Grantee: Fernando de Queiroz Cunha
• Support Opportunities: Research Projects - Thematic Grants