Role of interleukin-6 in chronic muscle hyperalgesic priming

Abstract

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 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 produce a markedly prolonged mechanical hyperalgesia. We now report that intramuscular injection of IL-6 produced mechanical hyperalgesia, lasting several hours, that was prevented by intrathecal injection of antisense to gp130, an IL-6 receptor subunit. Furthermore, following complete recovery from intramuscular IL-6-induced hyperalgesia, intramuscular PGE 2 produced a mechanical hyperalgesia that was remarkably prolonged compared to naïve controls, indicating the presence of chronic latent hyperalgesia. This ability of IL-6 to produce chronic latent hyperalgesia was prevented by intrathecal admininstration of antisense for gp130. Furthermore, gp130 antisense also prevented chronic latent hyperalgesia produced by intramuscular 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.

Fibromyalgia and obesity: the hidden link

“…Okifuji et al [29] reported that obesity in FMS is related to the greater levels of proinflammatory indices. Results from animal research strongly support the involvement of proinflammatory cytokines in central sensitization [66] and the development of chronic latent hyperalgesia in muscles [67].…”

Bradykinin and Nerve Growth Factor Play Pivotal Roles in Muscular Mechanical Hyperalgesia after Exercise (Delayed-Onset Muscle Soreness)

“…However, the causal relationships among cytokines, pain, and other changes have not been analyzed. As to the role of cytokines, Dina et al (2008) reported an interesting mechanism in which IL-6, after acutely inducing mechanical hyperalgesia, primes later prolongation of muscle mechanical hyperalgesia induced by another agent. In our present results, upregulation of IL-6 was observed at some time points, but anti-IL-6 antibody failed to reverse the developed mechanical hyperalgesia after LC.…”

Stress Induces a Switch of Intracellular Signaling in Sensory Neurons in a Model of Generalized Pain

“…Because fibromyalgia syndrome affects the muscles, we tested whether there is increased sensitivity to immune mediator, PGE 2 in muscle in the sound-stressed rats compared with nonstressed controls. Mechanical nociceptive threshold in the gastrocnemius muscle was quantified using a digital force transducer (Chatillon; model DFI2; Amtek) (Dina et al, 2008). Rats were restrained in a vented tubular Plexiglas holder with slated openings on the side that allow easy access to the hindlimb.…”