Methotrexate suppresses substance p and CGRP in Adjuvant arthritis in rats

Mahmood Ahmed, Mohammad Perwaiz Iqbal, Jawed Altaf Balg, R. Rehman, Ayaz Alam Qureshi

Research output: Contribution to journalArticlepeer-review


The mechanism by which methotrexate (MTX) produces its anti-inflammatory effect in rheumatoid arthritis (RA) is not completely clear. The objective of this study was to investigate whether the anti-inflammatory effect of MTX is through its influence on the expression of sensory neuropeptides, substance P (SP) and calcitonin gene-related peptide (CGRP) in ankle joints and dorsal root ganglia (DRG) of arthritic rats. Adjuvant arthritis was induced with heat-killed mycobacteria. One group of arthritic rats (n=6) was treated with MTX (0.2 mg/kg body weight, subcutaneously) on every 4th day for a period of 18 weeks, while another group of arthritic rats (n=6) treated with physiological saline served as control. After 18-week treatment, animals were sacrificed and the inflamed ankle joints and corresponding DRG (L2-L6) were dissected and prepared for immunohistochemical analysis. The neuronal density of SP and CGRP immunoreactivity in ankle joints and DRG was assessed by semi-quantitative analysis. There was significant reduction in hind paw swelling and inflammation in the MTX-treated rats SP-and CGRP-positive nerve fibres were significantly reduced (P<0.05) in ankle joints in MTX treated rats as compared to control rats. Similarly, CGRP-positive nerve cells in DRG were significantly decreased (/,=0.0004) in rats treated with MTX as compared to controls. In rats with adjuvant arthritis, MTX significantly reduced CGRP expression in the ankle joints and their corresponding DRG and SP expression in ankle joints. Suppression of pro-inflammatory neuropeptides, SP and CGRP may be another mechanism by which MTX produces its anti-inflammatory effect in arthritis.

Original languageEnglish
Pages (from-to)162-168
Number of pages7
JournalJournal of the Chemical Society of Pakistan
Issue number1
Publication statusPublished - Feb 2009


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