Cytokine involvement in dynorphin-induced allodynia

Dynorphin A is an endogenous opioid peptide, which has previously been shown to produce a long-lasting allodynia and hyperalgesia in mice, behavioral states consistent with signs of clinically observed neuropathic pain. This dynorphin-induced allodynia was used as a pharmacological, central model of neuropathic pain. In this study, we examined the involvement of the cytokine LL-1 beta, the transcription factor nuclear factor kappa B (NF-kappa B), and de novo protein synthesis in the development of allodynia induced by intrathecal (i.t.) administration of dynorphin in male ICR mice. Pretreatment with the protein synthesis inhibitor cycloheximide (0.3-85 nmol), the NF-kappa B inhibitor pyrrolidinedithiocarbamate (PDTC) (0.001-1000 pmol), the lL-1 receptor antagonist (IL-1ra) protein (0.01-100 ng), the caspase-1 inhibitor (YVAD) (0.1-300 pmol), and the anti-inflammatory cytokine IL-10 (0.1-300 ng) all dose-dependently reduced the induction of dynorphin-induced allodynia. Finally, IL-10 administered within the first 24 h after the dynorphin insult prevented the development of chronic allodynia. These results demonstrate that the anti-inflammatory cytokines IL-10 and IL-1ra impede the development of dynorphin-induced allodynia. These results also suggest that production of new proteins through NF-kappa B activation is required for the induction of allodynia. We speculate that IL-1ra, IL-10, PDTC and cycloheximide, interfere with the central pro-inflammatory cascade. Modulation of cytokine activity in the spinal cord may therefore prove to be an effective therapeutic strategy for the treatment of chronic pain. (C) 2000 International Association for the Study of Pain. Published by Elsevier Science B.V.