Role of prostaglandins on sensory transduction

本研究旨在研究鞘内注射前列腺素E_1和前列腺素F_2α和前列腺素F_2对伤害性躯体、伤害性内脏和非伤害性躯体刺激相关的不同类型感觉信息传递的影响。甩尾试验用于测量对伤害性躯体刺激的反应，结直肠扩张试验用于检测对伤害性内脏刺激的反应。测量Semmes-Weinstein单丝(SWMS)对机械压力的收缩反应，以评估其对非伤害性机械躯体刺激的敏感性。吗啡(1-10 mg)、巴氯芬(0.1-1.0 mg)或生理盐水，于静脉注射前列腺素F_(2α)(100 Ng)前30分钟经腰穿导管注入。在注射前列腺素F_2α后3小时、24小时和48小时重复测量。甩尾潜伏期短时间内(10%至…鞘内注射前列腺素E_1 500 ng或前列腺素F_2 100 ng后20分钟以上。与这些短期效应形成鲜明对比的是，三种不同强度的SWMS(0.217、0.745和2.35g)在给予PGE_1和PGF_2α&gt；后，产生的兴奋评分(痛觉异常)有较长时间的增加。SWMS的激越分数的变化依赖于PGs的剂量和刺激强度。吗啡和巴氯芬以剂量和时间依赖的方式抑制前列腺素F_2α和巴氯芬引起的痛觉过敏，而生理盐水则无此作用。最大剂量吗啡可在120~180min内使痛觉过敏症状基本缓解，之后过敏状态恢复至生理盐水对照组水平。相比之下，接受1杯巴氯芬治疗的7人中，有5人在48小时内没有出现痛觉过敏。给药后48h，PGs组大鼠脊髓组织学与生理盐水组无明显差异，提示PGs可在脊髓水平引起感觉加工通路的超敏(痛觉过敏和/或痛觉过敏)状态。它们还表明，在PGs的直接作用消失后，PGs产生的非有害信息而不是有害信息的加工过程中的长期变化继续存在。脊髓内GABA_B受体系统可能参与了PGF_2α和GT_2诱导的痛觉过敏的发生。较少

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