Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2010 Sep;32(5):819-25.
doi: 10.1111/j.1460-9568.2010.07359.x. Epub 2010 Aug 19.

Eccentric exercise induces chronic alterations in musculoskeletal nociception in the rat

Pedro Alvarez  1 , Jon D Levine, Paul G Green
Affiliations

Eccentric exercise induces chronic alterations in musculoskeletal nociception in the rat

Pedro Alvarez et al. Eur J Neurosci. 2010 Sep.

Abstract

Eccentric muscle exercise is a common cause of acute and chronic (lasting days to weeks) musculoskeletal pain. To evaluate the mechanisms involved, we have employed a model in the rat, in which eccentric hind limb exercise produces both acute mechanical hyperalgesia as well as long-term changes characterized by enhanced hyperalgesia to subsequent exposure to an inflammatory mediator. Eccentric exercise of the hind limb produced mechanical hyperalgesia, measured in the gastrocnemius muscle, which returned to baseline at 120 h post-exercise. When nociceptive thresholds had returned to baseline, intramuscular injection of prostaglandin E(2) (PGE(2) ) induced hyperalgesia that was unattenuated 240 h later, much longer than PGE(2) -induced hyperalgesia in unexercised rats (4 h). This marked prolongation of PGE(2) hyperalgesia induced by eccentric exercise was prevented by the spinal intrathecal injection of oligodeoxynucleotide antisense to protein kinase Cε, a second messenger in nociceptors implicated in the induction of chronic pain. Exercise-induced hyperalgesia and prolongation of PGE(2) hyperalgesia were inhibited by the spinal intrathecal administration of antisense for the interleukin-6 but not the tumor necrosis factor α type 1 receptor. These findings provide further insight into the mechanism underlying exercise-induced chronic muscle pain, and suggest novel approaches for the prevention and treatment of exercise- or work-related chronic musculoskeletal pain syndromes.

PubMed Disclaimer

Figures

Figure 1
Figure 1. Eccentric exercise induces muscle hyperalgesia
The ipsilateral hind limb was exercised eccentrically for 15 min (filled squares) and after exercise mechanical nociceptive threshold of the gastrocnemius muscle in both hind limbs measured over time. Compared to contralateral limbs (filled circle) there was a significant decrease in nociceptive threshold in the vibrated limbs, which lasted at least 120 h post-exercise.
Figure 2
Figure 2. Eccentric exercise induces hyperalgesic priming
Seven days after eccentric exercise, following recovery of nociceptive threshold to pre-exercise baseline, PGE2 (1 μg) was injected into both the ipsilateral and contralateral gastrocnemius muscle. In non-exercised contralateral limbs (filled circles) PGE2-induced hyperalgesia had completely resolved within 4 h, while in the exercised limbs (filled squares), hyperalgesia was greatly prolonged, being undiminished 240 h after PGE2 administration.
Figure 3
Figure 3. PKCε antisense inhibits exercise-induced hyperalgesia
Intrathecal administration of ODN antisense against PKCε for 3 days before and 3 days after eccentric exercise suppressed the acute hyperalgesia in the exercised leg (open squares), while hyperalgesia was still present in exercised leg of mismatch ODN treated rats (filled squares). There was no significant effect of treatment in the contralateral limbs (two-way ANOVA F1,60 = 3.4; P = 0.095).
Figure 4
Figure 4. PKCε antisense inhibits exercise-induced hyperalgesic priming
In rats that had received ODN antisense against PKCε, for 3 days before and 3 days after vibration (open squares, n=6), PGE2–induced hyperalgesia returned to baseline by 4 h post PGE2, while in mismatch-treated rats (filled squares), PGE2 hyperalgesia remained elevated 240 h after exercise. There was no significant effect of treatment in the contralateral limbs (two-way ANOVA F1,70 = 0.4; P = 0.53).
Figure 5
Figure 5. IL-6 receptor antisense prevents exercise-induced hyperalgesia
In rats that received antisense ODN to gp130 (open squares) for 3 days prior and 3 days after exercise, hyperalgesia in the exercised leg was significantly less than in exercised leg of rats receiving mismatch ODN to gp130 (filled squares). There was a significant effect of treatment in the contralateral limbs (two-way ANOVA F1,60 = 6.5; P = 0.021), with a significant difference only at the 24 h time point (Bonferroni post-hoc test, P<0.001).
Figure 6
Figure 6. IL-6 receptor antisense prevents exercise-induced hyperalgesic priming
In rats that received ODN antisense to gp130 (open squares, n=6) for 3 days prior and 3 days after exercise, PGE2–induced hyperalgesia returned to baseline by 4 h post PGE2, in contrast to rats treated with mismatch ODN in which PGE2 produced hyperalgesia that remained enhanced 72 h after exercise. There was a significant effect of antisense treatment in the contralateral limbs (two-way ANOVA, F1,64 = 9.75; P = 0.007), with a significant difference only at the 4 h time point (Bonferroni post-hoc test, P<0.001).
Figure 7
Figure 7. TNFα type-1 receptor antisense does not prevent exercise-induced hyperalgesia
In rats that received ODN antisense to TNFα receptor type 1 (open squares) for 3 days prior and 3 days after exercise, hyperalgesia in the exercised leg was not significantly different compared to that in exercised leg of rats receiving mismatch ODN (filled squares; two-way ANOVA F1,90 = 0.4; P = 0.54). There was no significant effect of treatment in the contralateral limbs (two-way ANOVA F1,90 = 0.29; P = 0.600).
Figure 8
Figure 8. TNFα type-1 receptor antisense does not completely prevent exercise-induced hyperalgesic priming
In rats that received ODN antisense to TNFα receptor type-1 (open squares) for 3 days prior and 3 days after exercise, PGE2–induced hyperalgesia remained elevated 72 h post PGE2, similar to rats treated with mismatch ODN. However, hyperalgesia was significantly less at the 4 h time point in antisense- compared to mismatch-treated rats. There was no significant effect of treatment in the contralateral limbs (two-way ANOVA F1,60 = 0.04; P = 0.84).
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Al-Shatti T, Barr AE, Safadi FF, Amin M, Barbe MF. Increase in inflammatory cytokines in median nerves in a rat model of repetitive motion injury. J. Neuroimmunol. 2005;167:13–22. - PMC - PubMed
    1. Alessandri-Haber N, Dina OA, Yeh JJ, Parada CA, Reichling DB, Levine JD. Transient receptor potential vanilloid 4 is essential in chemotherapy-induced neuropathic pain in the rat. J. Neurosci. 2004;24:4444–4452. - PMC - PubMed
    1. Alessandri-Haber N, Yeh JJ, Boyd AE, Parada CA, Chen X, Reichling DB, Levine JD. Hypotonicity induces TRPV4-mediated nociception in rat. Neuron. 2003;39:497–511. - PubMed
    1. Aley KO, Levine JD. Multiple receptors involved in peripheral alpha 2, mu, and A1 antinociception, tolerance, and withdrawal. J. Neurosci. 1997;17:735–44. - PMC - PubMed
    1. Aley KO, Messing RO, Mochly-Rosen D, Levine JD. Chronic hypersensitivity for inflammatory nociceptor sensitization mediated by the epsilon isozyme of protein kinase C. J. Neurosci. 2000;20:4680–4685. - PMC - PubMed

Publication types

MeSH terms