Interleukin-1alpha has antiallodynic and antihyperalgesic activities in a rat neuropathic pain model

Nerve injury and the consequent release of interleukins (ILs) are processes implicated ill pain transmission. To study the potential role of IL-1 in the pathogenesis of allodynia and hyperalgesia, IL-1 alpha and comparative IL-1 beta, IL-6, and IL-10 mRNA levels were quantified using competitive RT-PCR Of the lumbar spinal cord and dorsal root ganglia (DRG; L5-L6) three and seven days after chronic constriction injury (CO) in rats. Microglial and astroglial activation in the ipsilateral spinal cord and DRG were observed after injury. In naive and CCI-exposed rats, IL-1alpha mRNA and protein were not detected in the spinal cord. IL-1beta and IL-6 mRNAs were strongly ipsilaterally elevated on day seven after CCI. In the ipsilateral DRG, IL-1alpha, IL-6, and IL-10 rnRNA levels were increased on days three and seven; IL-1beta was elevated only oil day seven. Western blot analysis revealed both the presence of IL-1alpha proteins (45 and 31 kDa) in the DRG and the down-regulation of these proteins after CCI Intrathecal administration or IL-1alpha (50-500 ng) in native rats did not influence nociceptive transmission, but IL-1beta (50-500 ng) induced hyperalgesia. In rats exposed to CCI, in IL-1alpha or IL-1 receptor antagonist dose-dependently attenuated symptoms of neuropathic pain; however, no effect of IL-1beta was observed. In sum, the first days after CCI showed it high abundance of IL-1alpha in the DRG. Together with the antiallodynic and antihyperalgesic effects observed after IL-1alpha administration, this finding indicates in important role for IL-1alpha in the development of neuropathic pain symptoms. (C) 2008 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.