An Experimental Evaluation of CORM-2 and Ifenprodil in Reducing Pain via Thalamic NMDAR-2B and BDNF Suppression in Chronic Polyarthritis Rats

Abstract

Rheumatoid arthritis (RA) pain is a debilitating symptom often persisting despite reduced inflammation, possibly due to dysregulated pain pathways. The study aimed to determine the effects of CORM-2 and Ifenprodil on nociceptive mechanisms involving NMDAR-2B and BDNF in thalamus of chronic polyarthritis rat mimicking RA. Eighty rats were randomly assigned into five groups: non-arthritic(N), arthritic control(A), arthritic groups treated with either CORM-2 (A+CORM-2), Ifenprodil (A+Ifenprodil), or Diclofenac (A+Diclofenac). Chronicpolyarthritis was induced by injecting complete Freund’s adjuvant (10mg/mL) in right footpad of the rats and intrathecal treatments were given for 7 days (Day-15 to Day-22). Pain behaviour tests evaluating tactile allodynia and thermal hyperalgesia development were conducted on Day-0 (baseline), Day-14 (pre-treatment), and Day-23 (post-treatment). Thalamus was collected for further molecular analyses. There was significant development of tactile allodynia and thermal hyperalgesia detected in arthritic rats (p<0.05) which were significantly reversed by CORM-2 and Ifenprodil treatments (p<0.05). Significant upregulation of mRNA level with increased BDNF and NMDAR-2B protein expression was detected in bilateral thalamic VPL regions (p<0.05). These proteins expression and mRNA levels were significantly reduced and downregulated with the treatments of CORM-2 and Ifenprodil (p<0.05).CORM-2 and Ifenprodil exert anti-nociceptive effects possibly by modulating thalamicnociceptive mechanisms through NMDAR-2B/BDNF signalling inhibition in chronic polyarthritis rat. This study provides insights into understanding possible mechanisms leading to RA pain for future therapeutic development and chronic pain management.