Effect of interleukin-1 beta on spinal cord nociceptive transmission of normal and monoarthritic rats after disruption of glial function

Introduction Cytokines produced by spinal cord glia after peripheral injuries have a relevant role in the maintenance of pain states. Thus, while IL-1 beta is overexpressed in the spinal cords of animals submitted to experimental arthritis and other chronic pain models, intrathecal administration of IL-1 beta to healthy animals induces hyperalgesia and allodynia and enhances wind-up activity in dorsal horn neurons. Methods To investigate the functional contribution of glial cells in the spinal cord nociceptive transmission, the effect of intrathecally administered IL-1 beta was studied in both normal and adjuvant-induced arthritic rats with or without glial inhibition. Four weeks after induction of monoarthritis, rats were treated with the glial cell inhibitor propentofylline (10 mu g i.t. daily during 10 days) and submitted to a C-fiber-mediated reflex paradigm evoked by single and repetitive (wind-up) electric stimulation. Results Both the propentofylline treatment and the monoarthritic condition modified the stimulating current required for threshold activation of C reflex responses. Intrathecal IL-1 beta increased spinal cord wind-up activity in normal and monoarthritic rats without propentofylline pre-treatment, but resulted in decreased wind-up activity in normal and monoarthritic propentofylline-treated animals. Intrathecal saline did not produce any effect. Thus, glial inactivation reverted into inhibition the excitatory effect of IL-1 beta on spinal cord wind-up, irrespective of the normal or monoarthritic condition of rats. Conclusions The results suggest that the excitatory effect of nanomolar doses of IL-1 beta on spinal wind-up in healthy rats is produced by an unidentified glial mediator, while the inhibitory effects of IL-1 beta on wind-up activity in animals with inactivated glia resulted from a direct effect of the cytokine on dorsal horn neurons. The present study failed to demonstrate a differential sensitivity of normal and monoarthritic rats to IL-1 beta administration into the spinal cord and to disruption of beta glial function, as both normal and monoarthritic animals changes wind-up activity in the same direction after propentofylline treatment, suggesting that after glial inhibition normal and monoarthritic animals behave similarly relative to the capability of dorsal horn neurons to generate wind-up activity when repeatedly stimulated by C-fibers.