Source
Laboratory of Neurobiology, Department of Biology, Faculty of Chemistry and Biology, University of Santiago of Chile, Ave. Libertador B. O'Higgins 3363, Casilla 40 Correo 33, Santiago, Chile. luis.constandil@usach.cl
Abstract
INTRODUCTION:
Cytokines produced by spinal cord glia after peripheral injuries have a relevant role in the maintenance of pain states. Thus, while IL-1beta is overexpressed in the spinal cords of animals submitted to experimental arthritis and other chronic pain models, intrathecal administration of IL-1beta 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-1beta 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 microg 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-1beta 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-1beta 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-1beta on spinal wind-up in healthy rats is produced by an unidentified glial mediator, while the inhibitory effects of IL-1beta 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-1beta 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.