N-acetylcysteine downregulates phosphorylated p-38 expression but does not reverse the increased superoxide anion levels in the spinal cord of rats with neuropathic pain

• Published in: Brazilian journal of medical and biological research Vol. 50; no. 2; p. e5801
• Main Authors: Horst, A, de Souza, J A, Santos, M C Q, Riffel, A P K, Kolberg, C, Ribeiro, M F M, de Fraga, L S, Partata, W A
• Format: Journal Article
• Language: English
• Published: Brazil Associacao Brasileira de Divulgacao Cientifica (ABDC) 01-01-2017; Associação Brasileira de Divulgação Científica
• Subjects: Acetylcysteine; Acetylcysteine - therapeutic use; Animals; Antinociception; BIOLOGY; Biomedical Sciences; Blotting, Western; Chronic constriction; Constriction, Pathologic; Disease Models, Animal; Dosage and administration; Down-Regulation - drug effects; Drug therapy; Gene expression; Genetic aspects; Health aspects; Male; Mechanical threshold; MEDICINE, RESEARCH & EXPERIMENTAL; Mitogen-activated protein kinase; Neuralgia - drug therapy; Neuralgia - etiology; p38 Mitogen-Activated Protein Kinases - drug effects; p38 Mitogen-Activated Protein Kinases - metabolism; Pain Threshold; Peripheral nervous system diseases; Phosphorylation - drug effects; Physiological aspects; Rats; Rats, Wistar; Sciatic functional index; Sciatic nerve; Spinal cord; Spinal Cord - drug effects; Spinal Cord - metabolism; Superoxides; Superoxides - metabolism; Mitogen-activated protein kinase; Sciatic functional index; Antinociception; Sciatic nerve; Chronic constriction; Mechanical threshold
• ISSN: 0100-879X; 1414-431X; 1414-431X
• DOI: 10.1590/1414-431X20165801

We determined the effect of N-acetylcysteine (NAC) on the expression of the phosphorylated p38 (p-p38) protein and superoxide anion generation (SAG), two important players in the processing of neuropathic pain, in the lumbosacral spinal cord of rats with chronic constriction injury (CCI)-induced neuropathic pain. The sciatic functional index (SFI) was also measured to assess the functional recovery post-nerve lesion. Thirty-six male Wistar rats were divided equally into the following groups: Naive (rats did not undergo surgical manipulation); Sham (rats in which all surgical procedures involved in CCI were used except the ligature), and CCI (rats in which four ligatures were tied loosely around the right common sciatic nerve), which received 2, 4, or 8 intraperitoneal injections of NAC (150 mg·kg-1·day-1) or saline beginning 4 h after CCI. Rats were sacrificed 1, 3, and 7 days after CCI. The SFI was measured on these days and the lumbosacral spinal cord was used for analysis of p-p38 expression and SAG. CCI induced a decrease in SFI as well as an increase in p-p38 expression and SAG in the spinal cord. The SFI showed a partial recovery at day 7 in saline-treated CCI rats, but recovery was improved in NAC-treated CCI rats. NAC induced a downregulation in p-p38 expression at all time-points evaluated, but did not reverse the increased SAG induced by CCI. Since p-p38 is a mediator in neuropathic pain and/or nerve regeneration, modulation of this protein may play a role in NAC-induced effects in CCI rats.