鞘内注射MK-801对炎性痛大鼠海马NOS表达及NO含量的影响

目的：观察鞘内给予N-甲基-D-天门冬氨酸（NMDA）受体拮抗剂MK-801对足底注射甲醛诱导的自发痛反应和海马一氧化氮合酶（NOS）表达及一氧化氮（N0）含量的影响,探讨炎性痛诱导海马NO产生增多的机制。方法：通过观察舔足反射时间反映大鼠自发痛程度;采用NADPH—d组织化学法测定大鼠海马NOS表达;硝酸还原酶法测定海马组织NO含量。结果：足底注射甲醛后动物即出现舔、咬、摇动注射侧脚掌等自发痛相关表现,预先鞘内注射MK-801可使大鼠第二时相自发病程度显著降低,但对第一时相痛反应程度无明显影响。注射甲醛后12h时,海马CA1、CA2～3区及DG区NOS阳性细胞数目、阳性细胞染色深度均显著增加,海马组织NO含量显著增加;预先鞘内注射MK-801,可使甲醛炎性痛大鼠海马各区NOS阳性细胞数目明显减少,阳性细胞染色深度明显变浅,海马NO含量明显降低。结论：鞘内注射MK-801可逆转甲醛炎性痛诱导的海马NOS表达及NO产生的增加,表明甲醛炎性痛诱导的海马NO产生增加主要是由于伤害性信息传入所引起。

Intrathecal injection of MK-801 inhibited the nos activity and no content of hippocampus in rat during the process of formalin-induced inflammatory pain

Aim： To study the effect of intrathecal injection of MK-801, a NMDA receptor antagonist, on the NOS activity and NO content of hippacampus in rat during the process of formalin-induced inflammatory pain as well as the pain behavior of rat. Methods： The degree of pain was determined by observing the time of licking and biting the injected paw. NOS expression in the hippocampus was determined by using NADPH- d histochemical staining. NO content of hippocampus was determined by assaying NO3^- and NO2^-. Results： Subcutaneous injection of formalin elicited a characteristic pain behaviottral response consisting of licking and biting the injected paw, etc. Intrathecal injection of MK-801 could shorten obviously the time of licking and biting representing pain behavioural response in phase 2. It is suggested that intmtheeal injection of MK-801 could block the pain behavioural response induced by formalin（ P 〈 0.05 ）. The number and staining degree of NADPH-d positive neurons in formalin group significantly increased at 12 h after the formalin injection in CA1, CA2 - 3 and DG of hippocampus compared with control group as well as NO content, however, the number and staining degree of NADPH-d positive neurons in formalin ＋ MK-801 group significantly decreased in contrast to those of formalin 12 h group as well as the NO content（ P 〈 0.01 ）. Conclusion： Intrathecal injection of NMDA receptor antagonist MK-801 could inhibit the NOS activity and NO production in hippocampus of rat, which showed the increase of hippocampal NO production was mainly induced by the peripheral nociceptive information input.