MK-801降低鞘内注射强啡肽A(1-17)对福尔马林诱导的大鼠痛反应的增强效应

本实验用福尔马林试验在动物痛模型上观察了鞘内单纯注射生理盐水 (NS)、NMDA受体阻断剂MK 80 1、阿片受体阻断剂纳洛酮 (naloxone)、强啡肽A DynA (1 17) ]以及先用MK 80 1或纳洛酮再注射DynA (1 17)对动物的行为痛反应的影响。大鼠后肢脚掌皮下注射福尔马林后出现的行为痛反应显示有 2个时相 ,即首先出现持续较短的第一时相和 3～ 6min后出现的持续较长的第二时相。实验结果显示 ,各组的第一时相无明显差异 ;而第二时相则有差异 :鞘内注射DynA (1 17)组第二时相痛反应持续时间 (489 5± 2 2 5s)明显较单纯鞘内注射NS组(3 44 7± 12 9s)、MK 80 1组 (3 3 1 4± 2 0 7s)和纳洛酮组 (3 5 2 5± 18 4s)长 (均为P <0 0 1) ;而先用NMDA受体阻断剂MK 80 1后再注射DynA (1 17) ,则第二时相行为痛反应的持续时间 (2 85 7± 19 4s)较单纯注射DynA (1 17)组明显缩短 (P <0 0 1) ,但与单纯鞘内注射MK 80 1组相比无明显差异 ;先用阿片受体阻断剂纳洛酮后再注射DynA (1 17) ,则动物的第二时相行为痛反应 (473 8± 17 8s)与单纯注射DynA (1 17)组相比无明显差异 ,而与单纯注射NS组或纳洛酮组相比则明显增强 (分别为P <0 0 1)。因此本实验结果提示 :(1)在脊髓水平的DynA(1 17)具有促进福尔马林所诱导的第二

MK-801 suppresses dynorphin A (1-17)-induced facilitation of nociceptive responses to formalin in rats

To explore the facilitation of nociceptive response by dynorphin (Dyn ) A in a model of formalin test in rats, the effects of single intrathecal injection (i.t.) of normal saline (NS), MK-801 (antagonist of NMDA receptor), naloxone (antagonist of opioid receptor), or Dyn A (1-17) were observed, and the effects of i.t. MK-801 or naloxone followed by i.t. Dyn A (1-17) were observed as well. The nociceptive licking and biting induced by injection of formalin exhibited two phases. The first phase lasted for a relatively short period of 3-9 min, and the second phase lasted for a relatively longer period after a 3 to 6- min quietness. The results showed that there were no differences in the first phase in all groups; however, there were differences in the second phase as follows: (1) the duration of nociceptive response was significantly increased in Dyn A (1-17) group (489.5+/-22.5 s) as compared to that of NS group (344.7+/-12.9 s), MK-801 group (331.4+/-20.7 s) or naloxone group (352.5+/-18.4 s) (P<0.01 in three cases); (2) the duration of nociceptive response was significantly shortened in MK-801 plus Dyn A (1-17) group (285.7+/-19.4 s) as compared to that of Dyn A (1-17) group (P<0.01), but there were no significant differences as compared to that of MK-801 group; and (3) there was no significant difference in the second phase between naloxone plus Dyn A (1-17) group (473.8+/-17.8 s) and Dyn A (1-17) group, but the duration of nociceptive response was longer than that of NS group or naloxone group (P<0.01 in both). The results obtained suggest: (1) at the spinal cord, Dyn A (1-17) facilitates nociceptive responses; (2) NMDA receptors, but not opioid receptors, are possibly involved in the nociception by Dyn A (1-17).