Prior voluntary wheel running attenuates neuropathic pain

Abstract

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.

High-fat diet and aging interact to produce neuroinflammation and impair hippocampal- and amygdalar-dependent memory

“…Based on prior data demonstrating that voluntary wheel running attenuates the inflammatory response to bacterial infection, stress, and surgery (Barrientos, et al, 2011, Grace, et al, 2016, Speaker, et al, 2014), here we assessed whether voluntary exercise in aged rats would prevent hippocampal- and amygdala-dependent memory impairments caused by HFD, and if it would do this by altering levels of IL-1β (n=6 in each group). Rats ran an average of ~100 meters per day over 6 weeks, as we have reported previously (Barrientos, et al, 2011).…”

Depression of home cage wheel running: a reliable and clinically relevant method to assess migraine pain in rats

“…Although depression of wheel running provides an objective and clinically relevant measure of migraine pain, exercise itself has been shown to reduce pain [11]. However, this type of exercise-induced antinociception typically requires multiple weeks of daily wheel running [24].…”

How does physical activity modulate pain?

“…Voluntary wheel running prior to induction of either chronic muscle pain or neuropathic pain prevented the development of hyperalgesia [6;14], suggesting a protective effect of physical activity. Further, regular physical activity and exercise reduces excitability of central neurons, measured by phosphorylation of the NR1 subunit of the NMDA receptor, alters neuroimmune signaling in the central nervous system, and increases release of endogenous opioids and serotonin in the brainstem pain inhibitory pathways [2;14;15].…”