Muscle inflammation induces a protein kinase Cepsilon-dependent chronic-latent muscle pain.
Skeletal muscle injuries can induce chronic pain, but the underlying mechanism is unknown. One possible cause has been suggested to be an increased sensitivity to inflammatory mediators. We demonstrate that self-limited inflammatory hyperalgesia induced by intramuscular carrageenan (lasting approximately 5 days) results in a state of chronic-latent hyperalgesia, revealed by injection of prostaglandin E(2) (PGE(2)) 10 days after carrageenan at the same site. In carrageenan-pretreated muscle, PGE(2) produced hyperalgesia that was unattenuated even 14 days after injection, markedly longer than the 4-hour hyperalgesia induced by PGE(2) in naive rats. This chronic-latent hyperalgesia was reversed as well as prevented by spinal intrathecal injection of oligodeoxynucleotide antisense to protein kinase Cepsilon, a second messenger implicated in long-lasting plasticity in cutaneous nociceptors.


CONCLUSIONS
We describe a novel experimental model for chronic muscle pain, produced by mild acute muscle inflammation, that has clinical significance since it has the potential to reveal cellular processes by which acute inflammation or muscle trauma underlies chronic muscle pain.
Dina
Olayinka A
OA
Department of Oral and Maxillofacial Surgery, University of California San Francisco, San Francisco, California 94143, USA.
Levine
Jon D
JD
Green
Paul G
PG
D000818:Animals; D002351:Carrageenan / Q000009:adverse effects; D002908:Chronic Disease; D015232:Dinoprostone / Q000378:metabolism / Q000494:pharmacology; D004195:Disease Models, Animal; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D006930:Hyperalgesia / Q000139:chemically induced / Q000201:enzymology / Q000503:physiopathology; D007273:Injections, Intramuscular; D007278:Injections, Spinal; D008297:Male; D018482:Muscle, Skeletal / Q000201:enzymology* / Q000294:innervation / Q000503:physiopathology; D009220:Myositis / Q000139:chemically induced / Q000201:enzymology* / Q000503:physiopathology; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D009475:Neurons, Afferent / Q000187:drug effects / Q000201:enzymology; D009619:Nociceptors / Q000187:drug effects / Q000201:enzymology* / Q000503:physiopathology; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology; D010146:Pain / Q000139:chemically induced / Q000201:enzymology* / Q000503:physiopathology; D051744:Protein Kinase C-epsilon / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D020319:Oligodeoxyribonucleotides, Antisense; D002351:Carrageenan; D051744:Protein Kinase C-epsilon; D015232:Dinoprostone