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Running wheel exercise induces therapeutic and preventive effects on inflammatory stimulus-induced persistent hyperalgesia in mice.

ABSTRACT: Chronic pain affects significant portion of the world's population and physical exercise has been extensively indicated as non-pharmacological clinical intervention to relieve symptoms in chronic pain conditions. In general, studies on pain chronification and physical exercise intervention have focused on neuropathic pain, although chronic pain commonly results from an original inflammatory episode. Based on this, the objective of the present study was to investigate the therapeutic and preventive effect of the running wheel exercise on the persistent hyperalgesia induced by repetitive inflammatory stimulus, a rodent model that simulates clinical conditions of chronic pain that persist even with no more inflammatory stimulus present. To evaluate the therapeutic effect of physical exercise, we first induced persistent hyperalgesia through 14 days of PGE2 hind paw injections and, after that, mice have access to the regular voluntary running wheel. To evaluate the preventive effect of physical exercise, we first left the mice with access to the regular voluntary running wheel and, after that, we performed 14 days of PGE2 hind paw injection. Our results showed that voluntary running wheel exercise reduced persistent mechanical and chemical hyperalgesia intensity induced by repetitive inflammatory stimulus. In addition, we showed that this therapeutic effect is long-lasting and is observed even if started belatedly, i.e. two weeks after the development of hyperalgesia. Also, our results showed that voluntary running wheel exercise absolutely prevented persistent mechanical and chemical hyperalgesia induction. We can conclude that physical exercise has therapeutic and preventive effect on inflammatory stimulus-induced persistent hyperalgesia. Our data from animal experiments bypass placebo effects bias of the human studies and reinforce physical exercise clinical recommendations to treat and prevent chronic pain.

SUBMITTER: Sartori CR

PROVIDER: S-EPMC7553300 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Running wheel exercise induces therapeutic and preventive effects on inflammatory stimulus-induced persistent hyperalgesia in mice.

Sartori Cesar Renato CR Pagliusi Marco M Bonet Ivan José Magayewski IJM Tambeli Claudia Herrera CH Parada Carlos Amilcar CA

PloS one 20201013 10

Chronic pain affects significant portion of the world's population and physical exercise has been extensively indicated as non-pharmacological clinical intervention to relieve symptoms in chronic pain conditions. In general, studies on pain chronification and physical exercise intervention have focused on neuropathic pain, although chronic pain commonly results from an original inflammatory episode. Based on this, the objective of the present study was to investigate the therapeutic and preventi ...[more]

PMID: 33048957

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Project description:Chemotherapy-induced cognitive impairment (chemobrain) and muscle wasting (cachexia) are persisting side effects which adversely affect the quality of life of cancer survivors. We therefore investigated the efficacy of physical exercise as a non-pharmacological intervention to reverse the adverse effects of chemotherapy. We examined whether physical exercise in terms of voluntary wheel running could prevent chemotherapy-induced cognitive and motor impairments in mice treated with the multi-kinase inhibitor sorafenib. Adult male BALB/c mice were subdivided into runner and non-runner groups and orally administered with sorafenib (60 mg/kg) or vehicle continuously for four weeks. Mice could freely access the running wheel anytime during sorafenib or vehicle treatment. We found that sorafenib treatment reduced body weight gain (% of change, vehicle: 3.28 ± 3.29, sorafenib: -9.24 ± 1.52, p = 0.0004), impaired hippocampal-dependent spatial memory in the Y maze (exploration index, vehicle: 35.57 ± 11.38%, sorafenib: -29.62 ± 7.90%, p < 0.0001), increased anhedonia-like behaviour in the sucrose preference test (sucrose preference, vehicle: 66.57 ± 3.52%, sorafenib: 44.54 ± 4.25%, p = 0.0005) and impaired motor skill acquisition in rotarod test (latency to fall on day 1: 37.87 ± 8.05 and day 2: 37.22 ± 12.26 s, p > 0.05) but did not induce muscle wasting or reduce grip strength. Concomitant voluntary running reduced anhedonia-like behaviour (sucrose preference, sedentary: 44.54 ± 4.25%, runners: 59.33 ± 4.02%, p = 0.0357), restored impairment in motor skill acquisition (latency to fall on day 1: 50.85 ± 15.45 and day 2: 168.50 ± 37.08 s, p = 0.0004), but failed to rescue spatial memory deficit. Immunostaining results revealed that sorafenib treatment did not affect the number of proliferating cells and immature neurons in the hippocampal dentate gyrus (DG), whereas running significantly increased cell proliferation in both vehicle- (total Ki-67+ cells, sedentary: 16,687.34 ± 72.63, exercise: 3320.03 ± 182.57, p < 0.0001) and sorafenib-treated mice (Ki-67+ cells in the ventral DG, sedentary: 688.82.34 ± 38.16, exercise: 979.53 ± 73.88, p < 0.0400). Our results suggest that spatial memory impairment and anhedonia-like behaviour precede the presence of muscle wasting, and these behavioural deficits are independent of the changes in adult hippocampal neurogenesis. Running effectively prevents body weight loss, improves motor skill acquisition and reduces anhedonia-like behaviour associated with increased proliferating cells and immature neurons in DG. Taken together, they support physical exercise rehabilitation as an effective strategy to prevent chemotherapy side effects in terms of mood dysregulation and motor deficit.

Dataset Information

Running wheel exercise induces therapeutic and preventive effects on inflammatory stimulus-induced persistent hyperalgesia in mice.

Publications

Running wheel exercise induces therapeutic and preventive effects on inflammatory stimulus-induced persistent hyperalgesia in mice.

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