Monosodium iodoacetate-induced osteoarthritis produces pain-depressed wheel running in rats: Implications for preclinical behavioral assessment of chronic pain

Stevenson, Glenn W.; Mercer, Hannah; Cormier, Jim; Dunbar, Catherine; Benoit, Laura; Adams, Chloe; Jezierski, Justin; Luginbuhl, Amy; Bilsky, Edward J.

doi:10.1016/j.pbb.2010.12.009

Cited by 72 publications

(66 citation statements)

References 28 publications

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“…Higher rates of running can be achieved in male rats with an acquisition period of 21 days (Stevenson et al, 2011); however, our data show that male rats reach stable levels of running and meet the criterion of 400 revolutions/day within 8 days. A short acquisition period (i.e., 3 days) results in greater variability with fewer rats reaching stable running levels.…”

Section: Discussioncontrasting

confidence: 60%

Home cage wheel running is an objective and clinically relevant method to assess inflammatory pain in male and female rats

Kandasamy

Calsbeek

Morgan

2016

Journal of Neuroscience Methods

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Background The assessment of nociception in preclinical studies is undergoing a transformation from pain-evoked to pain-depressed tests to more closely mimic the effects of clinical pain. Many inflammatory pain-depressed behaviors (reward seeking, locomotion) have been examined, but these tests are limited because of confounds such as stress and difficulties in quantifying behavior. New Method The present study evaluates home cage wheel running as an objective method to assess the magnitude and duration of inflammatory pain in male and female rats. Results Injection of Complete Freund’s Adjuvant (CFA) into the right hindpaw to induce inflammatory pain almost completely inhibited wheel running for 2 days in males and females. Wheel running gradually returned to baseline levels within 12 days despite persistent mechanical hypersensitivity (von Frey test). Comparison with Existing Methods Continuously monitoring home cage wheel running improves on previous studies examining inflammatory pain-depressed wheel running because it is more sensitive to noxious stimuli, avoids the stress of removing the rat from its cage for testing, and provides a complete analysis of the time course for changes in nociception. Conclusions The present data indicate that home cage wheel running is a clinically relevant method to assess inflammatory pain in the rat. The decrease in activity caused by inflammatory pain and subsequent gradual recovery mimics the changes in activity caused by pain in humans. The tendency for pain-depressed wheel running to be greater in female than male rats is consistent with the tendency for women to be at greater risk of chronic pain than men.

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Section: Discussioncontrasting

confidence: 60%

Home cage wheel running is an objective and clinically relevant method to assess inflammatory pain in male and female rats

Kandasamy

Calsbeek

Morgan

2016

Journal of Neuroscience Methods

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“…16,24,62 When voluntary wheel running was initiated after CCI in this study, distance travelled did not correlate with von Frey thresholds at any timepoint. This result suggests that unrestricted voluntary wheel running is not an alternative pain measure for CCI.…”

Section: Discussionmentioning

confidence: 52%

Prior voluntary wheel running attenuates neuropathic pain

Grace

Fabisiak

Green‐Fulgham

et al. 2016

Pain

111

158

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Exercise is known to exert a systemic anti-inflammatory influence, but whether its effects are sufficient to protect against subsequent neuropathic pain is underinvestigated. We report that 6 weeks of voluntary wheel running terminating before chronic constriction injury (CCI) prevented the full development of allodynia for the ∼3-month duration of the injury. Neuroimmune signaling was assessed at 3 and 14 days after CCI. Prior exercise normalized ipsilateral dorsal spinal cord expression of neuroexcitatory interleukin (IL)-1β production and the attendant glutamate transporter GLT-1 decrease, as well as expression of the disinhibitory P2X4R-BDNF axis. The expression of the macrophage marker Iba1 and the chemokine CCL2 (MCP-1), and a neuronal injury marker (activating transcription factor 3), was attenuated by prior running in the ipsilateral lumbar dorsal root ganglia. Prior exercise suppressed macrophage infiltration and/or injury site proliferation, given decreased presence of macrophage markers Iba1, iNOS (M1), and Arg-1 (M2; expression was time dependent). Chronic constriction injury–driven increases in serum proinflammatory chemokines were suppressed by prior running, whereas IL-10 was increased. Peripheral blood mononuclear cells were also stimulated with lipopolysaccharide ex vivo, wherein CCI-induced increases in IL-1β, nitrite, and IL-10 were suppressed by prior exercise. Last, unrestricted voluntary wheel running, beginning either the day of, or 2 weeks after, CCI, progressively reversed neuropathic pain. This study is the first to investigate the behavioral and neuroimmune consequences of regular exercise terminating before nerve injury. This study suggests that chronic pain should be considered a component of “the diseasome of physical inactivity,” and that an active lifestyle may prevent neuropathic pain.

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“…The weight exerted on each hind limb (measured in grams) was evaluated over a period of 5 s. The final measurement of the weight distribution was given by the average of three measurements. Changes in the distribution were calculated as follows 16,17 .…”

Section: Joint Assessment Of Disability (Weight Bearing Test)mentioning

confidence: 99%

Osteoarthritis model induced by intra-articular monosodium iodoacetate in rats knee

et al. 2016

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PURPOSE:To evaluate the usefulness of a knee osteoarthritis model through functional, radiological and microscopic changes of the synovial membrane. METHODS:Forty eight rats were divided randomly into two groups. The first received 0.9% saline in the joint and corresponded to the control group. The second was submitted to experimental osteoarthritis of the right knee induced by monosodium iodoacetate and corresponded to the osteoarthritis group. All animals were subjected to comparative tests of forced ambulation and joint movements, inability to articulate and tactile allodynia on day 1 post-experiment by forced ambulation (Roto-rod test), joint assessment of disability (weight bearing test) and assessment of tactile allodynia (Von Frey test). After inflammatory induction they were divided into four subgroups corresponding to the scheduled death in 7, 14, 21 and 28 days when they were submitted to radiographic examination of the knee, arthrotomy and collection of the synovial membrane. RESULTS:The osteoarthritis group showed significant differences compared to control group on days 7 and 14 in Roto-rod, in weight bearing and Von Frey tests in all days, and in radiological evaluation. Microscopic examination of the synovial membrane showed abnormalities of inflammatory character at all stages. CONCLUSION:The osteoarthritis induced by intra-articular monosodium iodoacetate in rats knee is a good model to be used in related research, because it provides mensurable changes on joint movements, tactile allodynia, progressive radiological degeneration and microscopic inflammation of the synovial membrane, that represent markers for osteoarthritis evaluation

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Monosodium iodoacetate-induced osteoarthritis produces pain-depressed wheel running in rats: Implications for preclinical behavioral assessment of chronic pain

Cited by 72 publications

References 28 publications

Home cage wheel running is an objective and clinically relevant method to assess inflammatory pain in male and female rats

Home cage wheel running is an objective and clinically relevant method to assess inflammatory pain in male and female rats

Prior voluntary wheel running attenuates neuropathic pain

Osteoarthritis model induced by intra-articular monosodium iodoacetate in rats knee

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