Effects of Treadmill Exercise on Advanced Osteoarthritis Pain in Rats

Arthritis Rheumatol. 2017 Jul;69(7):1407-1417. doi: 10.1002/art.40101. Epub 2017 Jun 5.


Objective: Exercise is commonly recommended for patients with osteoarthritis (OA) pain. However, whether exercise is beneficial in ameliorating ongoing pain that is persistent, resistant to nonsteroidal antiinflammatory drugs (NSAIDs), and associated with advanced OA is unknown.

Methods: Rats treated with intraarticular (IA) monosodium iodoacetate (MIA) or saline underwent treadmill exercise or remained sedentary starting 10 days postinjection. Tactile sensory thresholds and weight bearing were assessed, followed by radiography at weekly intervals. After 4 weeks of exercise, ongoing pain was assessed using conditioned place preference (CPP) to IA or rostral ventromedial medulla (RVM)-administered lidocaine. The possible role of endogenous opioids in exercise-induced pain relief was examined by systemic administration of naloxone. Knee joints were collected for micro-computed tomography (micro-CT) analysis to examine pathologic changes to subchondral bone and metaphysis of the tibia.

Results: Treadmill exercise for 4 weeks reversed MIA-induced tactile hypersensitivity and weight asymmetry. Both IA and RVM lidocaine D35, administered post-MIA, induced CPP in sedentary but not exercised MIA-treated rats, indicating that exercise blocks MIA-induced ongoing pain. Naloxone reestablished weight asymmetry in MIA-treated rats undergoing exercise and induced conditioned place aversion, indicating that exercise-induced pain relief is dependent on endogenous opioids. Exercise did not alter radiographic evidence of OA. However, micro-CT analysis indicated that exercise did not block lateral subchondral bone loss or trabecular bone loss in the metaphysis, but did block MIA-induced medial bone loss.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Anesthetics, Local / pharmacology
  • Animals
  • Arthralgia / physiopathology*
  • Arthritis, Experimental / chemically induced
  • Arthritis, Experimental / diagnostic imaging
  • Arthritis, Experimental / physiopathology*
  • Behavior, Animal / drug effects*
  • Disease Models, Animal
  • Enzyme Inhibitors / toxicity
  • Hyperalgesia / chemically induced
  • Hyperalgesia / physiopathology*
  • Injections, Intra-Articular
  • Iodoacetic Acid / toxicity
  • Knee Joint / diagnostic imaging
  • Knee Joint / drug effects*
  • Knee Joint / physiopathology
  • Lidocaine / pharmacology
  • Male
  • Medulla Oblongata
  • Naloxone / pharmacology
  • Narcotic Antagonists / pharmacology
  • Osteoarthritis, Knee / chemically induced
  • Osteoarthritis, Knee / diagnostic imaging
  • Osteoarthritis, Knee / physiopathology*
  • Physical Conditioning, Animal*
  • Rats
  • Rats, Sprague-Dawley
  • Tibia / diagnostic imaging
  • Weight-Bearing
  • X-Ray Microtomography


  • Anesthetics, Local
  • Enzyme Inhibitors
  • Narcotic Antagonists
  • Naloxone
  • Lidocaine
  • Iodoacetic Acid