Role of interleukin-6 in chronic muscle hyperalgesic priming.
After recovery from acute muscle pain even minor subsequent muscle use can initiate recurrence of the same mechanical hyperalgesia months or years after the initial injury. We have recently developed a model of this chronic latent hyperalgesia in the rat. In this study, we have examined the possibility that interleukin-6 (IL-6), an inflammatory mediator produced during acute muscle inflammation, can mediate the production of this chronic latent hyperalgesic state in which subsequent exposure to inflammatory mediators produces a markedly prolonged mechanical hyperalgesia. We now report that i.m. injection of IL-6 produced mechanical hyperalgesia, lasting several hours, that was prevented by intrathecal injection of antisense to glycoprotein 130 (gp130), an IL-6 receptor subunit. Furthermore, following complete recovery from i.m. IL-6-induced hyperalgesia, i.m. prostaglandin E(2) produced a mechanical hyperalgesia that was remarkably prolonged compared with naïve controls, indicating the presence of chronic latent hyperalgesia. This ability of IL-6 to produce chronic latent hyperalgesia was prevented by intrathecal administration of antisense for gp130. Furthermore, gp130 antisense also prevented chronic latent hyperalgesia produced by i.m. injection of the inflammogen, carrageenan. These results identify a role for IL-6 in acute inflammatory muscle pain and as a potential target against which therapies might be directed to treat chronic muscle pain.
Dina
O A
OA
Department Oral and Maxillofacial Surgery, University of California San Francisco, San Francisco, CA 94143, USA.
Green
P G
PG
Levine
J D
JD
D000704:Analysis of Variance; D000818:Animals; D002351:Carrageenan / Q000009:adverse effects; D004195:Disease Models, Animal; D006930:Hyperalgesia / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology*; D007375:Interleukin-1 / Q000009:adverse effects / Q000378:metabolism*; D015850:Interleukin-6 / Q000009:adverse effects; D008297:Male; D009132:Muscles; D020319:Oligodeoxyribonucleotides, Antisense / Q000008:administration & dosage; D010147:Pain Measurement / Q000379:methods; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D019947:Receptors, Interleukin-6 / Q000737:chemistry
D007375:Interleukin-1; D015850:Interleukin-6; D020319:Oligodeoxyribonucleotides, Antisense; D019947:Receptors, Interleukin-6; D002351:Carrageenan