Birder L A, de Groat W C
University of Pittsburgh, PA 15261, USA. Lbirder+@pitt.edu
Somatosens Mot Res. 1998;15(1):5-12. doi: 10.1080/08990229870916.
Previous studies have revealed that chemical irritation of the urinary bladder and urethral mucosa increases the expression of the immediate-early gene, c-fos, in the lumbosacral spinal cord of the rat. The present experiments were undertaken to determine whether drugs known to suppress bladder reflex pathways or spinal nociceptive mechanisms would influence c-fos expression induced by chemical irritation of the lower urinary tract (LUT). Capsaicin (100 mg/kg subcutaneous (s.c.), 7 days prior to the experiment) which does not block bladder reflexes but does desensitize C-fiber afferents, reduced (89%) the number of Fos-positive cells in the lumbosacral spinal cord induced by acetic acid-induced irritation of the LUT. Morphine (2.5 mg/kg, intravenous (i.v.)) or a low dose of baclofen, a GABA(B) agonist, both of which markedly suppressed reflex bladder activity, did not alter spinal c-fos expression induced by LUT irritation. However, a larger dose of baclofen (10 mg/kg, i.v.) reduced by 45% the number of Fos-positive cells. Clonidine (200 microg/kg, i.v.), an alpha2 adrenergic agonist, depressed bladder reflexes but produced only a small decrease (25%) in c-fos expression in lateral laminae V-VII of the cord. The ganglionic blocking agent, hexamethonium, which blocks autonomic but not afferent pathways to the LUT, decreased c-fos expression by 50%. The results indicate that certain drugs can differentially affect reflex bladder activity and c-fos expression and that analgesic drugs which suppress somatic nociceptive pathways do not necessarily affect the c-fos expression induced by visceral nociceptive input.
先前的研究表明，对大鼠膀胱和尿道黏膜进行化学刺激会增加大鼠腰骶脊髓中即早基因c-fos的表达。本实验旨在确定已知可抑制膀胱反射通路或脊髓伤害性感受机制的药物是否会影响下尿路（LUT）化学刺激诱导的c-fos表达。辣椒素（实验前7天皮下注射（s.c.）100 mg/kg）虽不阻断膀胱反射，但会使C纤维传入神经脱敏，可减少（89%）乙酸诱导的LUT刺激所引起的腰骶脊髓中Fos阳性细胞的数量。吗啡（静脉注射（i.v.）2.5 mg/kg）或低剂量的巴氯芬（一种GABA(B)激动剂），二者均能显著抑制膀胱反射活动，但并未改变LUT刺激诱导的脊髓c-fos表达。然而，较大剂量的巴氯芬（静脉注射10 mg/kg）可使Fos阳性细胞数量减少45%。可乐定（静脉注射200 μg/kg），一种α2肾上腺素能激动剂，可抑制膀胱反射，但仅使脊髓V-VII层外侧的c-fos表达略有下降（25%）。神经节阻断剂六甲铵可阻断至LUT的自主神经通路但不阻断传入神经通路，可使c-fos表达降低50%。结果表明，某些药物可对膀胱反射活动和c-fos表达产生不同影响，且抑制躯体伤害性感受通路的镇痛药不一定会影响内脏伤害性传入所诱导的c-fos表达。
