Effects of Treadmill Exercise on Advanced Osteoarthritis Pain in Rats

Abstract

Objective Exercise is commonly recommended for patients with osteoarthritis (OA) pain. However, whether exercise is beneficial in ameliorating persistent NSAID-resistant ongoing pain associated with advanced OA is unknown. Methods Rats treated with intra-articular monosodium iodoacetate (MIA) or saline underwent treadmill exercise or remained sedentary starting 10 days post-injection. Tactile sensory thresholds and weight bearing were assessed followed by radiographs at weekly intervals. After 4 weeks of exercise, ongoing pain was assessed using conditioned place preference (CPP) to intra-articular or rostral ventromedial medulla (RVM) lidocaine. The possible role of endogenous opioids in exercise-induced pain relief was examined by systemic administration of naloxone. Knee joints were collected for μCT analysis to examine pathological changes to subchondral bone and metaphysis of the tibia. Results Treadmill exercise for 4 weeks reversed MIA-induced tactile hypersensitivity and weight asymmetry. Both intra-articular and RVM lidocaine D35 post-MIA induced CPP in sedentary but not exercised MIA-treated rats, indicating that exercise blocks MIA-induced ongoing pain. Naloxone re-established weight asymmetry in MIA-treated rats undergoing exercise and induced conditioned place aversion (CPA), indicating exercise-induced pain relief is dependent on endogenous opioids. Exercise did not alter radiographic evidence of OA. However, μCT analysis indicates that exercise blocked MIA-induced medial, but not lateral subchondral bone loss and trabecular bone loss in the metaphysis. Conclusion These findings support the conclusion that exercise induces pain relief in advanced, NSAID resistant OA, likely through increased endogenous opioid signaling. In addition, treadmill exercise blocked MIA-induced bone loss in this model, indicating a potential bone stabilizing effect of exercise on the OA joint.

Comparison of the effects of exercise with chondroitin sulfate on knee osteoarthritis in rabbits

“…CS exerts its anti-inflammatory effects through the inhibition of reactive oxygen species activity or the activation of protein kinases, reducing the synthesis of proteolytic enzymes (mmp-3, mmp-9, and mmp-13), inflammation-related enzymes (pla2, cox-2, nos-2), and proinflammatory factors (il-1β and tnf-α) [ 6 , 7 ]. In this study, administration of CS reduced the expression of mRNA for mmp-13, il-1, and adamts-5 ( p < 0.01), which concurs with previous [ 32 ] studies.…”

Mechanism of exercise-induced analgesia: what we can learn from physically active animals

“… 13 , 24 , 62 , 120 , 137 , 160 More recently, these behavioral effects have been replicated in exercise models of treadmill running, voluntary wheel running and resistance training as well as in pain models of noninflammatory muscle pain, neuropathic pain, arthritic pain, and glutamate-induced pain. 1 , 6 , 16 , 47 , 58 , 93 , 106 , 107 , 147 Specifically, 8 weeks of voluntary running wheel activity blocked the production of hyperalgesia in a model of noninflammatory muscle pain. Naloxone administered systemically or directly into the periaqueductal gray (PAG) or the rostral ventral medial medulla (RVM), 2 brain locations important in endogenous opioid system, blocked these analgesic effects, whereas systemic injection of naloxone methiodide, a peripherally acting opioid antagonist, had no effect suggesting the central but not peripheral effects of exercise on mediating the endogenous opioid system 16 (Fig.…”

“…Exercise has also shown to be beneficial for pain relief in less widely studied pain models including osteoarthritis, 1 , 38 incisional pain model, 29 , 30 inflammatory pain model, 45 , 76 , 86 , 125 complex regional pain syndrome, 106 intervertebral disk degeneration (IDD), 101 immobilization-induced pain, 33 , 112 chronic stress-induced pain, 132 ischemia and reperfusion, 128 glutamate-induced pain, 107 and experimental autoimmune encephalomyelitis 7 , 110 (Tables 1 and 2 ). Although behavioral data are important for demonstrating the analgesic effects of exercise, understanding the mechanisms through which physical activity is producing these effects will be beneficial for future development of therapeutic targets for pain reduction.…”

Pulsed Electromagnetic Fields to Influence Pain Relief Following Knee Osteoarthritis in Rats

“…Exercise is the most commonly recommended intervention in osteoarthritis because surgeries such as total knee replacement may not be optimal in younger populations with osteoarthritis due to its expensive cost and side effects [3,12]. A recent meta-analysis indicated that running has protective effects against knee joint surgery in OA; moreover, exercise also unmasked the protective and pain-alleviating effects [13,14]. Similarly, we observed that the TE group demonstrated less expression of c-fos than the CON7 group.…”