Regular exercise reverses sensory hypersensitivity in a rat neuropathic pain model: Role of endogenous opioids

Nicola J. Stagg, Heriberto P. Mata, Mohab M. Ibrahim, Erik J Henriksen, Frank Porreca, Todd W Vanderah, T. Philip Malan

Research output: Contribution to journalArticle

131 Citations (Scopus)

Abstract

Background: Exercise is often prescribed as a therapy for chronic pain. Short-term exercise briefly increases the production of endogenous analgesics, leading to transient antinociception. In limited studies, exercise produced sustained increases in endogenous opioids, sustained analgesia, or diminished measures of chronic pain. This study tests the hypothesis that regular aerobic exercise leads to sustained reversal of neuropathic pain by activating endogenous opioid-mediated pain modulatory systems. Methods: After baseline measurements, the L5 and L6 spinal nerves of male Sprague-Dawley rats were tightly ligated. Animals were randomized to sedentary or 5-week treadmill exercise-trained groups. Thermal and tactile sensitivities were assessed 23 h after exercise, using paw withdrawal thresholds to von Frey filaments and withdrawal latencies to noxious heat. Opioid receptor antagonists were administered by subcutaneous, intrathecal, or intracerebroventricular injection. Opioid peptides were quantified using immunohistochemistry with densitometry. Results: Exercise training ameliorated thermal and tactile hypersensitivity in spinal nerve-ligated animals within 3 weeks. Sensory hypersensitivity returned 5 days after discontinuation of exercise training. The effects of exercise were reversed by using systemically or intracerebroventricularly administered opioid receptor antagonists and prevented by continuous infusion of naltrexone. Exercise increased β-endorphin and met-enkephalin content in the rostral ventromedial medulla and the mid-brain periaqueductal gray area. Conclusions: Regular moderate aerobic exercise reversed signs of neuropathic pain and increased endogenous opioid content in brainstem regions important in pain modulation. Exercise effects were reversed by opioid receptor antagonists. These results suggest that exercise-induced reversal of neuropathic pain results from an up-regulation of endogenous opioids.

Original languageEnglish (US)
Pages (from-to)940-948
Number of pages9
JournalAnesthesiology
Volume114
Issue number4
DOIs
StatePublished - Apr 2011

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Neuralgia
Opioid Analgesics
Narcotic Antagonists
Hypersensitivity
Exercise
Spinal Nerves
Hot Temperature
Touch
Chronic Pain
Endorphins
Pain
Methionine Enkephalin
Periaqueductal Gray
Naltrexone
Opioid Peptides
Densitometry
Analgesia
Brain Stem
Sprague Dawley Rats
Analgesics

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

Cite this

Regular exercise reverses sensory hypersensitivity in a rat neuropathic pain model : Role of endogenous opioids. / Stagg, Nicola J.; Mata, Heriberto P.; Ibrahim, Mohab M.; Henriksen, Erik J; Porreca, Frank; Vanderah, Todd W; Malan, T. Philip.

In: Anesthesiology, Vol. 114, No. 4, 04.2011, p. 940-948.

Research output: Contribution to journalArticle

Stagg, Nicola J. ; Mata, Heriberto P. ; Ibrahim, Mohab M. ; Henriksen, Erik J ; Porreca, Frank ; Vanderah, Todd W ; Malan, T. Philip. / Regular exercise reverses sensory hypersensitivity in a rat neuropathic pain model : Role of endogenous opioids. In: Anesthesiology. 2011 ; Vol. 114, No. 4. pp. 940-948.
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