ALLODYNIA EVOKED BY INTRATHECAL ADMINISTRATION OF PROSTAGLANDIN E(2) TO CONSCIOUS MICE
ALLODYNIA EVOKED BY INTRATHECAL ADMINISTRATION OF PROSTAGLANDIN E(2) TO CONSCIOUS MICE
复制标题
DOI：
10.1016/0304-3959(94)90226-7
复制
发表时间：
1994-05-01
期刊：
影响因子：
7.4
通讯作者：
HAYAISHI, O
中科院分区：
文献类型：
--
作者：
MINAMI, T;UDA, R;HAYAISHI, O
我们最近报道，对有意识的小鼠鞘内 (i.t.) 施用前列腺素 (PG) F-2 α 会诱发异常性疼痛，这种疼痛是由无害性刷牙胁腹引起的。在本研究中，我们证明 i.t.对有意识的小鼠施用 PGD(2) 和 PGE(2) 也会导致异常性疼痛。 PGD(2)对异常性疼痛的剂量依赖性显示出偏斜的钟形模式(0.1ng-2.5μg/小鼠)，并且在鞘内注射15分钟后观察到最大异常性疼痛效果为1.0μg。 PGD(2)诱导的异常性疼痛表现出与PGF(2α)诱导相似的时程和剂量依赖性，但得分较低。另一方面，PGE(2)对异常性疼痛的剂量依赖性在10fg至2.0μg/小鼠的宽剂量范围内显示出钟形模式。在it后5分钟观察到0.01-0.1μg的最大异常性疼痛效果。注射后，反应在50分钟的实验时间内逐渐下降。鞘内注射马钱子碱和 GABA(A) 拮抗剂荷包牡丹碱也能在清醒小鼠中引起异常性疼痛。士的宁和荷包牡丹碱引起的异常性疼痛的时间进程分别与PGE(2)和PGF(2α)引起的异常疼痛的时间进程一致。 PGE(2) 诱发的异常性疼痛可通过士的宁敏感性甘氨酸受体激动剂牛磺酸、NMDA 受体拮抗剂氯胺酮和高剂量的 α(2)-肾上腺素能激动剂可乐定以剂量依赖性缓解，但不能通过 GABA(A) 激动剂蝇蕈醇或 GABA(B) 激动剂巴氯芬缓解。相比之下，可乐定和巴氯芬可显着抑制PGF(2α)诱导的异常性疼痛，但牛磺酸、氯胺酮或蝇蕈醇则不能抑制这种异常性疼痛。此外，通过热板试验评估的PGE(2)诱导的痛觉过敏并未被牛磺酸或可乐定抑制。这些结果证明PGE(2)诱导的异常性疼痛的机制不同于PGF(2α)诱导的异常性疼痛和PGE(2)诱导的痛觉过敏。
We recently reported that intrathecal (i.t.) administration of prostaglandin (PG) F-2 alpha to conscious mice induced allodynia that was elicited by non-noxious brushing of the flanks, In the presents study, we demonstrate that i.t. administration of PGD(2) and PGE(2) to conscious mice also results in allodynia. Dose dependency of PGD(2) for allodynia showed a skewed bell-shaped pattern (0.1 ng-2.5 mu g/mouse), and the maximal allodynic effect was observed with 1.0 mu g at 15 min after intrathecal injection. PGD(2)-induced allodynia showed a time course and dose dependency similar to that induced by PGF(2 alpha), but with lower scores. On the other hand, dose dependency of PGE(2) for allodynia showed a bell-shaped pattern over a wide range of dosage from 10 fg to 2.0 mu g/mouse. The maximal allodynic effect was observed with 0.01-0.1 mu g at 5 min after i.t. injection, and the response gradually decreased over the experimental period of 50 min. Intrathecally administered strychnine and the GABA(A) antagonist bicuculline also induced allodynia in conscious mice. The time courses of allodynia evoked by strychnine and bicuculline coincided with those by PGE(2) and PGF(2 alpha) respectively. PGE(2)-induced allodynia was dose-dependently relieved by the strychnine-sensitive glycine receptor agonist taurine, the NMDA receptor antagonist ketamine, and a high dose of the alpha(2)-adrenergic agonist clonidine, but not by the GABA(A) agonist muscimol or by the GABA(B) agonist baclofen. In contrast, PGF(2 alpha)-induced allodynia was dramatically inhibited by clonidine and baclofen, but not by taurine, ketamine or muscimol. In addition, PGE(2)-induced hyperalgesia assessed by the hot plate test was not suppressed by taurine or clonidine. These results demonstrate that the mechanism of PGE(2)-induced allodynia is different from that of PGF(2 alpha)-induced allodynia and from that of PGE(2)-induced hyperalgesia.