Eccentric exercise induces chronic alterations in musculoskeletal nociception in the rat.
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.
Alvarez
Pedro
P
Department of Oral and Maxillofacial Surgery, University of California San Francisco, San Francisco, CA 94143-0440, USA.
Levine
Jon D
JD
Green
Paul G
PG
D000818:Animals; D015232:Dinoprostone / Q000494:pharmacology; D004195:Disease Models, Animal; D006614:Hindlimb / Q000187:drug effects / Q000503:physiopathology; D006930:Hyperalgesia / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D018482:Muscle, Skeletal / Q000503:physiopathology; D009140:Musculoskeletal Diseases / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology / Q000627:therapeutic use; D010146:Pain / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D010805:Physical Conditioning, Animal / Q000502:physiology*; D051744:Protein Kinase C-epsilon / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors; D000093242:Interleukin-6 Inhibitors
D015232:Dinoprostone; D020319:Oligodeoxyribonucleotides, Antisense; D051744:Protein Kinase C-epsilon; D014409:Tumor Necrosis Factor-alpha; D000093242:Interleukin-6 Inhibitors