Muscle Inflammation Induces a Protein Kinase Cε–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 ∼5 days) results in a state of chronic-latent hyperalgesia, revealed by injection of prostaglandin E2 (PGE2) 10 days after carrageenan at the same site. In carrageenan-pretreated muscle, PGE2 produced hyperalgesia that was unattenuated even 14 days after injection, markedly longer than the 4-hour hyperalgesia induced by PGE2 in naive rats. This chronic-latent hyperalgesia was reversed as well as prevented by spinal intrathecal injection of oligodeoxynucleotide antisense to protein kinase Cε, a second messenger implicated in long-lasting plasticity in cutaneous nociceptors.PerspectiveWe 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.