Recent behavioral and electrophysiological studies have attributed an important role to dorsal root reflexes (DRRs) in the initiation and development of
neurogenic inflammation produced by intradermal
capsaicin (CAP). The DRRs can occur in peptidergic fibers, resulting in peripheral release of neuromediators that produce vasodilation, plasma extravasation and subsequently
hyperalgesia and
allodynia. In this study, we have evaluated the effect of spinal administration of
bumetanide (a blocker of the Na+-K+-2Cl- cotransporter, NKCC) on DRR activity, changes in cutaneous blood flow (vasodilation), hindpaw
edema,
mechanical allodynia, and
hyperalgesia induced by
intradermal injection of 1% CAP in Sprague-Dawley rats. Vasodilation was monitored using
laser Doppler flowmetry, neurogenic
edema was evaluated by measurements of hindpaw volume, and secondary
mechanical allodynia and hyperalesia were tested using von Frey filaments (10 and 200 mN) applied to the plantar surface of the paw. Changes in the blood flow were blocked significantly by intrathecal
bumetanide at 10 and 100 microM in both pre- and posttreatment studies. Spinal
bumetanide at 10 and 100 microM blocked neurogenic
edema when it was administered before CAP injection, but only
bumetanide at 100 microM administered after CAP injection reduced the paw
edema significantly. Furthermore, the administration of
bumetanide onto the spinal cord reduced the increment in DRR activity produced by CAP. Finally, both secondary
mechanical allodynia and hyperalesia were reduced by
bumetanide at 1, 10, and 100 microM. Taken together these results suggest that NKCC is involved in the increases in DRR activity,
neurogenic inflammation and
hyperalgesia and
allodynia induced by intradermal CAP.