This article is part of the Topical Collection on Bone and Joint Pain
Physical activity is increasingly recommended for chronic pain. In this review, we briefly survey recent, high-quality meta-analyses on the effects of exercise in human chronic pain populations, followed by a critical discussion of the rodent literature.
Most meta-analytical studies on the effects of exercise in human chronic pain populations describe moderate improvements in various types of chronic pain, despite substantial variability in the outcomes reported in the primary literature. The most consistent findings suggest that while greater adherence to exercise programs produces better outcomes, there is minimal support for the superiority of one type of exercise over another. The rodent literature similarly suggests that while regular exercise reduces hypersensitivity in rodent models of chronic pain, exercise benefits do not appear to relate to either the type of injury or any particular facet of the exercise paradigm. Potential factors underlying these results are discussed, including the putative involvement of stress-induced analgesic effects associated with certain types of exercise paradigms.
Exercise research using rodent models of chronic pain would benefit from increased attention to the role of stress in exercise-induced analgesia, as well as the incorporation of more clinically relevant exercise paradigms.
Goldberg DS, McGee SJ. Pain as a global public health priority. BMC Public Health 2011;11:770.
Institute of Medicine (U.S.) Committee on Advancing Pain Research Care and Education. Relieving Pain in America: A blueprint for transforming prevention, care, education, and research. Washington (DC): national academies press; 2011.
Cross M, Smith E, Hoy D, Nolte S, Ackerman I, Fransen M, Bridgett L, Williams S, Guillemin F, Hill CL, Laslett LL, Jones G, Cicuttini F, Osborne R, Vos T, Buchbinder R, Woolf A, March L The global burden of hip and knee osteoarthritis: estimates from the global burden of disease 2010 study. Ann Rheum Dis 2014;73(7):1323–1330.
Centers for Disease C, Prevention. Prevalence of doctor-diagnosed arthritis and arthritis-attributable activity limitation—United States, 2010-2012. MMWR Morb Mortal Wkly Rep. 2013;62(44):869–73.
Lee J, Dunlop D, Ehrlich-Jones L, Semanik P, Song J, Manheim L, et al. Public health impact of risk factors for physical inactivity in adults with rheumatoid arthritis. Arthritis Care Res (Hoboken). 2012;64(4):488–93. CrossRef
Mehrotra C, Chudy N, Thomas V. Obesity and physical inactivity among Wisconsin adults with arthritis. WMJ. 2003;102(7):24–8. PubMed
Centers for Disease C, Prevention. National and state medical expenditures and lost earnings attributable to arthritis and other rheumatic conditions—United States, 2003. MMWR Morb Mortal Wkly Rep. 2007;56(1):4–7.
Buttgereit F, Burmester GR, Bijlsma JW. Non-surgical management of knee osteoarthritis: where are we now and where do we need to go? RMD Open. 2015;1(1):e000027.
Kroenke K, Krebs EE, Bair MJ. Pharmacotherapy of chronic pain: a synthesis of recommendations from systematic reviews. Gen Hosp Psychiat. 2009;31(3):206–19. CrossRef
McAlindon TE, Bannuru RR, Sullivan MC, Arden NK, Berenbaum F, Bierma-Zeinstra SM, et al. OARSI guidelines for the non-surgical management of knee osteoarthritis. Osteoarthr Cartilage. 2014;22(3):363–88. CrossRef
Howley ET. Type of activity: resistance, aerobic and leisure versus occupational physical activity. Med Sci Sport Exer. 2001;33(6):S364–S9. CrossRef
Durstine JL, Gordon B, Wang ZZ, Luo XJ. Chronic disease and the link to physical activity. J Sport Health Sci. 2013;2(1):3–11. CrossRef
Dobson JL, McMillan J, Li L. Benefits of exercise intervention in reducing neuropathic pain. Front Cell Neurosci. 2014;8
Cooney GM, Dwan K, Greig CA, Lawlor DA, Rimer J, Waugh FR, McMurdo M, Mead GE, Cochrane Common Mental Disorders Group Exercise for depression. Cochrane Db Syst Rev 2013(9).
Global status report on noncommunicable diseases . Geneva: World Health Organization; 2014.
Lim SS, Vos T, Flaxman AD, Danaei G, Shibuya K, Adair-Rohani H, et al. A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990-2010: a systematic analysis for the global burden of disease study 2010. Lancet. 2012;380(9859):2224–60. PubMedPubMedCentralCrossRef
Greenwood BN, Loughridge AB, Sadaoui N, Christianson JP, Fleshner M. The protective effects of voluntary exercise against the behavioral consequences of uncontrollable stress persist despite an increase in anxiety following forced cessation of exercise. Behav Brain Res. 2012;233(2):314–21. PubMedPubMedCentralCrossRef
Physical activity guidelines for Americans. Okla Nurse. 2008;53(4):25.
Osteoarthritis: National Clinical Guideline for Care and Management in Adults. National Institute for Health and Clinical Excellence: Guidance. London2008.
•• Geneen LJ, Moore RA, Clarke C, Martin D, Colvin LA, Smith BH. Physical activity and exercise for chronic pain in adults: an overview of Cochrane reviews. Cochrane Database Syst Rev. 2017;4:CD011279. Geneen et al. is a relevant and thorough overview of recent Cochrane reviews on the effects of exercise in human chronic pain populations. PubMed
Fransen M, McConnell S, Hernandez-Molina G, Reichenbach S. Exercise for osteoarthritis of the hip. Cochrane Database Syst Rev. 2014;4:CD007912.
O'Connor SR, Tully MA, Ryan B, Bleakley CM, Baxter GD, Bradley JM, McDonough SM Walking exercise for chronic musculoskeletal pain: systematic review and meta-analysis. Arch Phys Med Rehabil 2015;96(4):724–34 e3.
Regnaux JP, Lefevre-Colau MM, Trinquart L, Nguyen C, Boutron I, Brosseau L, et al. High-intensity versus low-intensity physical activity or exercise in people with hip or knee osteoarthritis. Cochrane Database Syst Rev. 2015;(10):CD010203.
• Juhl C, Christensen R, Roos EM, Zhang W, Lund H. Impact of exercise type and dose on pain and disability in knee osteoarthritis: a systematic review and meta-regression analysis of randomized controlled trials. Arthritis Rheumatol. 2014;66(3):622–36. Juhl et al. is an excellent systematic review and meta-regression analysis of randomized controlled trials on the effects of exercise intensity and type in knee osteoarthritis.–36.
Ettinger WH Jr, Burns R, Messier SP, Applegate W, Rejeski WJ, Morgan T, et al. A randomized trial comparing aerobic exercise and resistance exercise with a health education program in older adults with knee osteoarthritis. The fitness arthritis and seniors trial (FAST). JAMA. 1997;277(1):25–31. PubMedCrossRef
Sluka KA, O'Donnell JM, Danielson J, Rasmussen LA. Regular physical activity prevents development of chronic pain and activation of central neurons. J Appl Physiol (1985). 2013;114(6):725–33. CrossRef
•• Sabharwal R, Rasmussen L, Sluka KA, Chapleau MW. Exercise prevents development of autonomic dysregulation and hyperalgesia in a mouse model of chronic muscle pain. Pain. 2016;157(2):387–98. Sabharwal et al. is one of only two rodent studies incorporating stress measures. PubMedPubMedCentralCrossRef
• Stagg NJ, Mata HP, Ibrahim MM, Henriksen EJ, Porreca F, Vanderah TW, et al. Regular exercise reverses sensory hypersensitivity in a rat neuropathic pain model: role of endogenous opioids. Anesthesiology. 2011;114(4):940–8. Stagg et al. is a thorough assessment of the effects of various exercise parameters in rodent model of neuropathic pain.–8.
Kami K, Taguchi Ms S, Tajima F, Senba E. Improvements in impaired GABA and GAD65/67 production in the spinal dorsal horn contribute to exercise-induced hypoalgesia in a mouse model of neuropathic pain. Mol Pain. 2016;12:174480691662905. CrossRef
Wakaizumi K, Kondo T, Hamada Y, Narita M, Kawabe R, Narita H, et al. Involvement of mesolimbic dopaminergic network in neuropathic pain relief by treadmill exercise: a study for specific neural control with Gi-DREADD in mice. Mol Pain. 2016;12:174480691668156. CrossRef
•• Cormier J, Cone K, Lanpher J, Kinens A, Henderson T, Liaw L, et al. Exercise reverses pain-related weight asymmetry and differentially modulates trabecular bone microarchitecture in a rat model of osteoarthritis. Life Sci. 2017;180:51–9. Cormier et al. is one of the few rodent studies assessing the effects of exercise on trabecular bone microarchitecture in a rat model of osteoarthritis. PubMedPubMedCentralCrossRef
•• Pitcher MH, Tarum F, Rauf IZ, Low LA, Bushnell C. Modest amounts of voluntary exercise reduce pain- and stress-related outcomes in a rat model of persistent hind limb inflammation. J Pain. 2017;18(6):687–701. Pitcher et al. is one of only two rodent studies incorporating stress measures. PubMedPubMedCentralCrossRef
Rodnick KJ, Reaven GM, Haskell WL, Sims CR, Mondon CE. Variations in running activity and enzymatic adaptations in voluntary running rats. J Appl Physiol (1985). 1989;66(3):1250–7. CrossRef
• Hutchinson KJ, Gomez-Pinilla F, Crowe MJ, Ying Z, Basso DM. Three exercise paradigms differentially improve sensory recovery after spinal cord contusion in rats. Brain. 2004;127(Pt 6):1403–. Hutchison et al. is the only study to employ positive reinforcement to promote running behavior.–14. PubMedCrossRef
•• Allen J, Imbert I, Havelin J, Henderson T, Stevenson G, Liaw L, et al. Effects of treadmill exercise on advanced osteoarthritis pain in rats. Arthritis Rheumatol. 2017;69(7):1407–17. Allen et al. is one of the few rodent studies assessing the effects of exercise on trabecular bone microarchitecture in a rat model of osteoarthritis. In addition, innovative approaches of assessing persistence of pain are used (i.e. Conditioned place preference).–17.
Yamaoka S, Oshima Y, Horiuchi H, Morino T, Hino M, Miura H, et al. Altered gene expression of RNF34 and PACAP possibly involved in mechanism of exercise-induced analgesia for neuropathic pain in rats. Int J Mol Sci. 2017;18(9)
Kuo TB, Lin T, Yang CC, Li CL, Chen CF, Chou P. Effect of aging on gender differences in neural control of heart rate. Am J Phys. 1999;277(6 Pt 2):H2233–9.
•• Greenwood BN, Foley TE, Day HE, Campisi J, Hammack SH, Campeau S, et al. Freewheel running prevents learned helplessness/behavioral depression: role of dorsal raphe serotonergic neurons. J Neurosci. 2003;23(7):2889–98. Greenwood et al. explore the neurobiological correlates of reward in voluntary wheel running. PubMedCrossRef
Belke TW, Wagner JP. The reinforcing property and the rewarding aftereffect of wheel running in rats: a combination of two paradigms. Behav Process. 2005;68(2):165–72. CrossRef
Shephard RJ, Shek PN. Autoimmune disorders, physical activity, and training, with particular reference to rheumatoid arthritis. Exerc Immunol Rev. 1997;3:53–67. PubMed
Moraska A, Deak T, Spencer RL, Roth D, Fleshner M. Treadmill running produces both positive and negative physiological adaptations in Sprague-Dawley rats. Am J Physiol-Reg I. 2000;279(4):R1321–R9.
Noble EG, Moraska A, Mazzeo RS, Roth DA, Olsson MC, Moore RL, et al. Differential expression of stress proteins in rat myocardium after free wheel or treadmill run training. J Appl Physiol (1985). 1999;86(5):1696–701. CrossRef
Onodera K, Sakurada S, Furuta S, Yonezawa A, Hayashi T, Honma I, et al. Age-related differences in forced walking stress-induced analgesia in mice. Drugs Exp Clin Res. 2001;27(5–6):193–8. PubMed
Nakagawasai O, Tadano T, Tan No K, Niijima F, Sakurada S, Endo Y, et al. Changes in beta-endorphin and stress-induced analgesia in mice after exposure to forced walking stress. Methods Find Exp Clin Pharmacol. 1999;21(7):471–6. PubMed
Sakurada S, Onodera K, Katsuyama S, Yonezawa A, Arai K, Hayashi T, et al. Effects of forced walking stress on formalin-induced paw licking in mice. Methods Find Exp Clin Pharmacol. 1999;21(7):467–70. PubMed
Layne JN, Benton AH. Some speeds of small mammals. J Mammal. 1954;35(1):104–5. CrossRef
Garland T. The relation between maximal running speed and body mass in terrestrial mammals journal of zoology. London. 1983;199:157–70.
- The Impact of Exercise in Rodent Models of Chronic Pain
Mark Henry Pitcher
- Springer US
Neu im Fachgebiet Orthopädie und Unfallchirurgie
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