Mechanisms mediating vibration-induced chronic musculoskeletal pain analyzed in the rat.
While occupational exposure to vibration is a common cause of acute and chronic musculoskeletal pain, eliminating exposure produces limited symptomatic improvement, and reexposure precipitates rapid recurrence or exacerbation. To evaluate mechanisms underlying these pain syndromes, we have developed a model in the rat, in which exposure to vibration (60-80Hz) induces, in skeletal muscle, both acute mechanical hyperalgesia as well as long-term changes characterized by enhanced hyperalgesia to a proinflammatory cytokine or reexposure to vibration. Exposure of a hind limb to vibration-produced mechanical hyperalgesia measured in the gastrocnemius muscle of the exposed hind limb, which persisted for approximately 2 weeks. When nociceptive thresholds had returned to baseline, exposure to a proinflammatory cytokine or reexposure to vibration produced markedly prolonged hyperalgesia. The chronic prolongation of vibration- and cytokine-hyperalgesia was prevented by spinal intrathecal injection of oligodeoxynucleotide (ODN) antisense to protein kinase Cepsilon, a second messenger in nociceptors implicated in the induction and maintenance of chronic pain. Vibration-induced hyperalgesia was inhibited by spinal intrathecal administration of ODN antisense to receptors for the type-1 tumor necrosis factor-alpha (TNFalpha) receptor. Finally, in TNFalpha-pretreated muscle, subsequent vibration-induced hyperalgesia was markedly prolonged.


CONCLUSIONS
These studies establish a model of vibration-induced acute and chronic musculoskeletal pain, and identify the proinflammatory cytokine TNFalpha and the second messenger protein kinase Cepsilon as targets against which therapies might be directed to prevent and/or treat this common and very debilitating chronic pain syndrome.
Dina
Olayinka A
OA
Department of Oral and Maxillofacial Surgery, University of California San Francisco, San Francisco, California, USA.
Joseph
Elizabeth K
EK
Levine
Jon D
JD
Green
Paul G
PG
D000818:Animals; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D006614:Hindlimb / Q000187:drug effects / Q000503:physiopathology; D006930:Hyperalgesia / Q000209:etiology / Q000503:physiopathology; D007249:Inflammation / Q000209:etiology / Q000503:physiopathology; D018836:Inflammation Mediators / Q000494:pharmacology; D007278:Injections, Spinal; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects / Q000503:physiopathology; D009140:Musculoskeletal Diseases / Q000209:etiology* / Q000503:physiopathology*; D016273:Occupational Exposure / Q000009:adverse effects*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology / Q000627:therapeutic use; D010146:Pain / Q000209:etiology* / Q000503:physiopathology*; D017288:Pain Threshold / Q000502:physiology; D051744:Protein Kinase C-epsilon / Q000037:antagonists & inhibitors / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000037:antagonists & inhibitors / Q000235:genetics; D015290:Second Messenger Systems / Q000187:drug effects / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014732:Vibration / Q000009:adverse effects*
D016207:Cytokines; D018836:Inflammation Mediators; D016376:Oligonucleotides, Antisense; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha; D051744:Protein Kinase C-epsilon