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

Nurul Ajilah Mohamed Khir, Ain’ Sabreena Mohd Noh, Anani Aila Mat Zin, Idris Long, Norhayati Yusop, Che Aishah Nazariah Ismail

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). Chronic
polyarthritis 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 thalamic
nociceptive 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.


Keywords


N-methyl-D-aspartate-2B receptor, brain-derived neurotrophic factor, CORM-2, Ifenprodil

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ISSN : 1675-8161