Biochemistry & Pharmacology: Open Access
Open Access
ISSN: 2167-0501
+44-20-4587-4809
ISSN: 2167-0501
+44-20-4587-4809
Neha Munawar
Kuwait University, Kuwait
Posters & Accepted Abstracts: Biochem Pharmacol (Los Angel)
Statement of the Problem: Development of a painful sensory neuropathy sometimes limits the use of nucleoside reverse transcriptase inhibitors (NRTIs) in HIV/AIDS management. Cannabis has been reported in clinical trials to have efficacy in relieving painful HIV-associated sensory neuropathy. The purpose of this study is to evaluate whether the endocannabinoid system plays a role in NRTI-induced painful neuropathy. Methodology & Theoretical Orientation: Female BALB/c mice were treated with 25 mg/kg of 2â�?²,3â�?²-dideoxycytidine (ddC), a NRTI, to induce painful neuropathy. The expression of the endocannabinoid system molecules was evaluated by real-time PCR in the brain, spinal cord and paw skin at six days post ddC administration. The effects of the endocannabinoids, N-arachidonoyl ethanolamine (AEA), 2-arachidonoyl glycerol (2-AG), cannabinoid receptor antagonists, AM 251 and AM 630, and G proteincoupled receptor 55 antagonist ML193 on ddC-induced thermal hyperalgesia were evaluated using the hot plate test. Findings: Mice treated with ddC developed mechanical and cold allodynia, and thermal hyperalgesia. Treatment with ddC increased transcripts of phospholipase C-�?²1, but not of other enzymes involved in the synthesis of endocannabinoids, only in the paw skin compared to vehicle-treatment. The transcripts of the inactivating enzymes, fatty acid amide hydrolase and monoacyl glycerol, were downregulated only in the brain and paw skin, respectively, of ddC-treated mice. AEA and 2-AG had antihyperalgesic effects against ddC-induced thermal hyperalgesia, but had no effect in na�?¯ve mice. The antihyperalgesic activity of AEA was antagonized by AM251 and AM630, whereas the activity of 2-AG was antagonized by AM251 and ML193, but not by AM630. Conclusion & Significance: Our results show that ddC induces painful neuropathy, which is associated with dysregulation of the endocannabinoid system. Agonists of cannabinoid receptors could be useful therapeutic agents for the management of NRTI-induced painful sensory neuropathy.