交感传出在大鼠糖尿病性痛过敏中的作用

EFFECTS OF SYMPATHETIC EFFERENT IN DIABETIC HYPERALGESIA IN RAT

交感传出和前列腺素（ＰＧｓ）在周围神经不全损伤和炎症所引起的痛过敏中起重要作用，它们对糖尿病性痛过敏的影响尚不清楚。本工作先给大鼠腹腔注射６－羟多巴胺（６－ＯＨＤＡ）损毁交感节后神经元（ＳＰＧＮＳ）末梢后，再给予链脲佐菌素（ＳＴＺ）以建立６－ＯＨＤＡ糖尿病大鼠模型，在连续４周的观察中这组大鼠伤害性爪回缩阈值（ＮＰＷＴ）和甩尾反射潜伏期（ＴＦＬ）没有明显变化，而糖尿病组大鼠的痛阈显著降低，并伴有痛过敏。皮内注射ＮＡ可使糖尿病痛过敏大鼠的ＮＰＷＴ显著降低，酚妥拉明或育亨宾能使它们的ＮＰＷＴ明显升高，而哌唑嗪则不影响其ＮＰＷＴ。去甲肾上腺素（ＮＡ）和酚妥拉明不影响对照组大鼠的ＮＰＷＴ。给６－ＯＨＤＡ糖尿病组大鼠皮内注射ＮＡ或酚妥拉明都不能明显改变大鼠的ＮＰＷＴ。ＰＧＥ１，ＰＧＥ２和ＰＧＤ２能使对照组和糖尿病组大鼠的ＮＰＷＴ均明显降低、结果提示，ＳＰＧＮｓ末梢参与糖尿病大鼠的痛过敏，ＮＡ作用于ＳＰＧＮｓ末梢的突触前α２－受体，刺激ＳＰＧＮｓ末梢合成和释放ＰＧｓ增多，后者作用于初级传入伤害感受器，引起大鼠产生痛过敏。

While sympathetic efferents and prostaglandins (PGs) play an important role inhyperalgesia of partial injury of peripheral nerves and inflammation, whether these arealso involved in diabetic hyperalgesia is unknown. With intraperitoneal injection of 6-hydroxydopamine (6-OHDA) to eliminate effects of sympathetic postganglionic neurons (SPGNs) terminals, a model of diabetic rats with infused 6-OHDA could be set upby injection of streptozotocin (STZ). Nociceptive paw-withdrawal threshold (NPWT)and tail flick latency (TFL) in 6-OHDA/diabetic rats were not changed significantly inthe following four weeks. However, in diabetic group rats, pain threshold was decreased significantly and accompanied by development of hyperalgesia. NPWT was significantly decreased with noradrenaline (NA) in diabetic hyperalgesic rats and increased with phentolamine or yohimbine, but not by prazocin. In the control rats,NPWT are not changed significantly by NA or phentolamine, and in 6-OHDA/diabeticrats, neither NA nor phentolamine also affected on NPWT significantly. However,NPWT may be significantly decreased by PGEI, PGE2 and PGD2 in both the controland the diabetic hyperalgesic rats. The above results suggested that SPGNs terminals areinvolved in hyperalgesia of diabetic rats, NA accelerated synthesis of PGs and releasedby way of presynaptic effect on a2-adrenergic receptors at the SPGNs terminals, PGs,in turn, directly acted on the primary afferent nociceptors, producing hyperalgesia.