INTRATHECAL PROSTAGLANDIN E(1) PRODUCES A LONG-LASTING ALLODYNIC STATE

The existence of prostaglandin (PG) receptors in the spinal cord has b een demonstrated, but their role in sensory processing is not yet well defined. PGE(1) is widely used clinically as a vasodilator. The prese nt study was designed to investigate the effects of intrathecally admi nistered PGE(1) on the transmission of different types of sensory info rmation, including that associated with noxious somatic, noxious visce ral, and non-noxious somatic stimulation. The tail-flick (TF) test was employed to measure responses to noxious somatic stimuli, and the col orectal distension test was used to examine responses to noxious visce ral stimuli. Withdrawal response to mechanical pressure produced by Se mmes-Weinstein mono-filaments (SWMs) was measured as an assessment of sensitivity to non-noxious mechanical somatic stimulation. TF latencie s and colorectal distension thresholds decreased for a short time (10- 20 min) following the intrathecal (i.t.) administration of both 100 ng or 500 ng of PGE(1). In sharp contrast to these short duration effect s, there was a long-lasting increase in agitation scores (allodynia) p roduced by 3 different intensities of SWMs (0.217, 0.745 and 2.35 g) a fter administration of PGE(1). The changes in agitation scores to SWMs were dependent on the dose of PGE(1) and the intensity of stimulation . This increase of agitation score was seen when PGE(1) was administer ed through the i.t. catheter or by direct i.t. puncture and the increa se lasted for at least 2 days after drug administration. Intrathecal a dministration of saline, however, did not produce any changes in TF la tencies, colorectal distension thresholds, or agitation scores produce d by SWMs. No significant histological difference was seen between spi nal cords exposed to 500 ng PGE(1) and saline 48 h after drug administ ration. These results demonstrate that PGE(1) may trigger a hypersensi tive (allodynic and/or hyperalgesic) state in sensory processing pathw ays at the spinal level. They also indicate that long-lasting changes in processing of non-noxious, but not noxious, information produced by PGE(1) continues after the disappearance of the direct action of PGE( 1).