| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1995: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1994: ¥1,200,000 (Direct Cost: ¥1,200,000)
|
|---|
| Research Abstract |
The present study was designed to investigate the effects of intrathecally administered PGE_1 and PGF_<2alpha> 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 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. Morphine (1-10mug), baclofen (0.1-1.0mug), or saline was administered through the i.t.catheter implanted in the lumbar region, 30 min before i.t.injection of PGF_<2alpha> (100ng). Measurements were repeated for 3 hours and at 24 and 48 hours after injection of PGF_<2alpha>.
Tail flick latencies colorectal distension thresholds decreased for a short time (10 to
… More
20 min) following the intrathecal administration of both 500ng of PGE_1 or 100ng of PGF_<2alpha>. In sharp contrast to these short duration effects, there was a long-lasting increase in agitation scores (allodynia) produced by three different intensities of SWMs (0.217,0.745 and 2.35g) after administration of PGE_1 and PGF_<2alpha>. The changes in agitation scores to SWMs were dependent on the dose of PGs and the intensity of stimulation. Morphine and baclofen supressed the PGF_<2alpha>-induced allodynia in dose- and time-dependent fashion, while saline had no effect. The highest dose of morphine almost completely relieved the allodynia for 120-180 min, and after that, the hypersensitive state was restored to the level of saline control group. In contrast, five out of seven treated with 1 mug of baclofen showed no allodynia for 48 hrs. No significant histological difference was seen between spinal cords exposed to PGs and saline 48 hours after drug administration.
These results demonstrate that PGs 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 information, but not noxious information, produced by PGs continues after the disappearance of the direct action of PGs. GABA_B receptor system in the spinal cord may be involved in the initiation of PGF_<2alpha>-induced allodynia. Less
|
