Emerging intervention of antidepressant with DMARD in non-cancerous nociceptive persistent pain associated depression in FCA induced rheumatoid arthritic rats

Sudhakar Pachiappan,Sudaroli Murugaiyan,Sabarinath Chandrasekar

doi:10.1590/s2175-97902020000318852

Abstract

Rheumatoid arthritis (RA) is a chronic inflammatory disorder that causes pain, systemic complications and premature mortality. Depression has also been identified as a problem for persons with RA. This association remaining significant even after the degree of disease activity is controlled. In the present study, the efficacy of combination therapeutic effect of antidepressant (amitriptyline) with Disease Modifying Anti rheumatoid drug (leflunomide) was determined in rheumatoid arthritis pain associated depression in Freund’s complete adjuvant (FCA) induced arthritic rats. Drug treatment was started 9 days after induction of FCA induced arthritis in rats. The antiarthritic activity was assessed by measuring paw volume, weight-bearing, hematological, biochemical, serological parameters, Radiographic analysis and Histopathology of tibiotarsal joints. The antidepressant activity was assessed by Forced swimming test, Rota-rod test and confirmed by estimation of brain neuro transmitters (serotonin and norepinephrine) level. Results of this study revealed that leflunomide and amitriptyline combination showed more significant (p<0.001) antiarthritic and antidepressant action and leflunomide alone treatment showed significant (p<0.001) antiarthritic activity only as compared to arthritic control. The leflunomide and low dose amitriptyline combination found to be more effective in pain associated depression in rheumatoid arthritic rats.

Highlights

Rheumatoid arthritis (RA) is a systemic inflammatory chronic progressive and prototypical autoimmune disease
Attenuated Mycobacterium tuberculosis organism obtained from Indian Council of Medical Research (ICMR), Chennai. leflunomide marketed sample purchased from Cadila health care Ltd, Ahmedabad, amitriptyline purchased from Vashudha Pharma Chem Ltd., Chennai, and Biochemical diagnostic kit were from Merck Specialties Pvt
Freund’s complete adjuvant (FCA) is the complete form of Freud’s adjuvant and is composed of inactivated and dried Mycobacterium tuberculosis (MT) emulsified in mineral oil that is used as an immune- booster

Summary

Introduction

Rheumatoid arthritis (RA) is a systemic inflammatory chronic progressive and prototypical autoimmune disease. It may affect many tissues and organs but primarily attacks the synovial joints. Pain is one of the most important symptoms reported by RA patients (Merskey, 1979). This pain results from the arthritic tissue inflammation, the release of inflammatory mediatory mediators such as Depression in RA patients is associated with an increased level of pain. The causal relationship between pain and depression may act in both directions with pain increasing depression and depression increasing pain (Magni et al, 1994). Depression is associated with increased functional disability and burden in rheumatoid arthritis patients.

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Results

Conclusion