Modest Amounts of Voluntary Exercise Reduce Pain- and Stress-Related Outcomes in a Rat Model of Persistent Hind Limb Inflammation

Abstract

Aerobic exercise improves outcomes in a variety of chronic health conditions, yet the support for exercise-induced effects on chronic pain in humans is mixed. While many rodent studies have examined the effects of exercise on persistent hypersensitivity, the vast majority employed forced exercise paradigms that are known to be highly stressful. Since stress can also produce analgesic effects, we studied how voluntary exercise, known to reduce stress in healthy subjects, alters hypersensitivity, stress and swelling in a rat model of persistent hind paw inflammation. Our data indicate that voluntary exercise rapidly and effectively reduces both hypersensitivity and stress-related outcomes without altering swelling. Moreover, the level of exercise is unrelated to the analgesic and stress-reducing effects, suggesting that even modest amounts of exercise may impart significant benefit in persistent inflammatory pain states.

The Impact of Exercise in Rodent Models of Chronic Pain

“…The duration of the voluntary running paradigms ranged between 1 and 12 weeks, but most lasted between 2 and 4 weeks. Furthermore, only one study using voluntary exercise reported the average running velocity: Pitcher et al [ 100 ••] showed that the average velocity of both sham and OA groups was approximately 45 m/min, which is comparable to other studies using voluntary wheel running [ 102 •, 103 ]. On the other hand, the maximal velocity at which rodents were forced to run on treadmills ranged between 6 and 30 m/min.…”

“…In these studies, exercise was performed for between 20 and 60 min/day for 4–7 days/week. The six studies (15%) using voluntary wheel running generally allowed longer wheel access (2–24 h/day [ 87 , 97 , 98 , 99 ••, 100 ••] but see [ 101 ]) for 4–7 days per week. However, it should be noted that the actual running time in voluntary exercise paradigms is unknown because rodents do not necessarily engage in constant running during periods of wheel access.…”

A dose response study of the effect of prostaglandin E2 on thermal nociceptive sensitivity

“…Thermal hypersensitivity was assessed within 30 mins of an animal being injected using the method of Pitcher et al 2017 (18, 19). Briefly, latency to withdrawal from a radiant light beam was measured using a Plantar Test device (IITC Life Science) with a glass surface, heated to 30 °C.…”

Exercise reverses pain-related weight asymmetry and differentially modulates trabecular bone microarchitecture in a rat model of osteoarthritis

“…Voluntary wheel running in rodents has been shown to enhance muscle viability and bone strength [7–9], attenuate allodynia and elevated IL-1β levels in a model of neuropathic pain [10], and increase protective CD206 macrophage production in a model of muscle pain, and decrease pain- and stress-related measures in a model of inflammatory pain [11,12]. Although there is an increasing literature base on exercise-pain interactions [10,11,13,14], less is known about how the behavioral mechanism of wheel running acquisition duration (i.e., prior wheel running) affects the expression of chronic pain-like behavior.…”