An analysis and strategy is urgently needed to address the future of the posts that are now supported by DfID -- options include the integration of some posts into support budgets or setting horizons for winding up activities and absorbing ongoing responsibilities.
(10, 30 and 90 μg) induced dose-dependent inhibition of wind-up activity (ED50=52.06 μg i.t)., an effect that was prevented by 100 μg i.t. of luzindole.
Intrathecal IL-1β 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.
Representative traces for the effects of IL-1β administration on wind-up activity are shown in Figure 2c.
This intrathecal dose of IL-1β has been shown to increase C-fiber evoked responses and wind-up activity in spinal cords of normal rats [ 8, 9].
Afterwards, trains of 12 stimuli each at 1 Hz were delivered to the toes in order to develop wind-up activity.
Accordingly, upon analyzing the global effect of IL-1β on wind-up activity during the complete 40-minute period of testing (% change of AUCs), two-way ANOVA identified the propentofylline treatment, but not the monoarthritic condition, as a factor influencing the effect of IL-1β on wind-up activity in both normal and monoarthritic rats.
As previously reported, wind-up activity in dorsal horn neurons is a C-fiber-mediated synaptic potentiation phenomenon of particular importance for the development and maintenance of chronic pain [ 21], but the role of glia and cytokines on wind-up activity in arthritic animals has received little attention.
This observation suggests 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.
Afterwards, a basal recording of both integrated C-reflex responses and wind-up activity prior to the intrathecal administration of recombinant IL-1β (2 ng/10 μl, equivalent to 11.4 nM) or saline (10 μl).
Interestingly, the present results demonstrated that the intrathecal propentofylline pre-treatment turned the excitatory effect of IL-1β on spinal cord wind-up activity into inhibition, in both normal and monoarthritic rats.
