Animal models of chronic pain: Effect of repetitive joint movement on inflammation and pain in an animal model of monoarthritis

Abstract

Range of motion (ROM) exercises improve the function of arthritic joints and are thus often prescribed to patients suffering with rheumatoid arthritis. However, effects of ROM exercise on disease progression and pain have not been demonstrated. We investigated the effects of manipulating the arthritic joint on mechanical withdrawal threshold and inflammation in a CFA-induced animal model of monoarthritis. Repetitive daily joint movements for 5 days improved the range of joint movement. However, this also led to increased swelling of the ankle and increased plasma extravasation, a monitor of loss of vascular endothelial integrity. Sensory testing of the affected joint to mechanical stimulation demonstrated a profound and persisting decrease in withdrawal threshold to stimulation with von Frey hairs after repetitive joint movement. To determine the role of endogenous opioids in modulating this decrease in withdrawal threshold a non-specific opioid antagonist, naloxone, was administered and the effect of joint movement was determined. There was a marked decrease in withdrawal threshold on all days, indicating an anti-nociceptive role of endogenous opioids. Our results demonstrate an improvement in the range of movement of an arthritic joint after daily repetitive joint movement. Surprisingly, our study also revealed an exacerbation of inflammation and pain sensitivity in the arthritic joint following repetitive joint movement; endogenous opioid mechanisms appear to mask these changes. These data raise questions regarding the value of exercising arthritic joints in people with rheumatoid arthritis. Range of motion (ROM) exercises improve the function of arthritic joints and are thus often prescribed to patients suffering with rheumatoid arthritis. However, effects of ROM exercise on disease progression and pain have not been demonstrated. We investigated the effects of manipulating the arthritic joint on mechanical withdrawal threshold and inflammation in a CFA-induced animal model of monoarthritis. Repetitive daily joint movements for 5 days improved the range of joint movement. However, this also led to increased swelling of the ankle and increased plasma extravasation, a monitor of loss of vascular endothelial integrity. Sensory testing of the affected joint to mechanical stimulation demonstrated a profound and persisting decrease in withdrawal threshold to stimulation with von Frey hairs after repetitive joint movement. To determine the role of endogenous opioids in modulating this decrease in withdrawal threshold a non-specific opioid antagonist, naloxone, was administered and the effect of joint movement was determined. There was a marked decrease in withdrawal threshold on all days, indicating an anti-nociceptive role of endogenous opioids. Our results demonstrate an improvement in the range of movement of an arthritic joint after daily repetitive joint movement. Surprisingly, our study also revealed an exacerbation of inflammation and pain sensitivity in the arthritic joint following repetitive joint movement; endogenous opioid mechanisms appear to mask these changes. These data raise questions regarding the value of exercising arthritic joints in people with rheumatoid arthritis.