Intrathecal prostaglandin E 1 produces a long-lasting allodynic state

Abstract

The existence of prostaglandin (PG) receptors in the spinal cord has been demonstrated, but their role in sensory processing is not yet well defined. PGE 1 is widely used clinically as a vasodilator. The present study was designed to investigate the effects of intrathecally administered PGE 1 on the transmission of different types of sensory information, including that associated with noxious somatic, noxious visceral, and non-noxious somatic stimulation. The tail-flick (TF) test was employed to measure responses to noxious somatic stimuli, and the colorectal distension test was used to examine responses to noxious visceral stimuli. Withdrawal response to mechanical pressure produced by Semmes-Weinstein mono-filaments (SWMs) was measured as an assessment of sensitivity to non-noxious mechanical somatic stimulation. TF latencies 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 effects, there was a long-lasting increase in agitation scores (allodynia) produced by 3 different intensities of SWMs (0.217, 0.745 and 2.35 g) after 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 administered through the i.t. catheter or by direct i.t. puncture and the increase lasted for at least 2 days after drug administration. Intrathecal administration of saline, however, did not produce any changes in TF latencies, colorectal distension thresholds, or agitation scores produced by SWMs. No significant histological difference was seen between spinal cords exposed to 500 ng PGE 1 and saline 48 h after drug administration. These results demonstrate that PGE 1 may trigger a hypersensitive (allodynic and/or hyperalgesic) state in sensory processing pathways 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.