Kolhekar R, Meller S T, Gebhart G F
Department of Pharmacology, University of Iowa, Iowa City 52242.
Neuroscience. 1993 Nov;57(2):385-95. doi: 10.1016/0306-4522(93)90070-v.
The effects of N-methyl-D-aspartate (100 amol-1 nmol) on the nociceptive tail-flick reflex were studied in awake rats. Lesser doses of N-methyl-D-aspartate (100 amol-10 pmol) administered intrathecally to the lumbar spinal cord produced a dose-dependent facilitation of the tail-flick reflex (maximum at 0.5-1 min). The greatest dose tested (1 nmol) inhibited the tail-flick reflex (maximum at 2-5 min) and produced a caudally directed scratching and biting behavior accompanied by vocalizations. Intrathecal pretreatment with the N-methyl-D-aspartate receptor antagonist, D-2-amino-5-phosphonovaleric acid (1 fmol-1 pmol), which produced no change in baseline tail-flick latency, blocked all N-methyl-D-aspartate produced effects in a dose-dependent manner (100 fmol D-2-amino-5-phosphonovaleric acid produced maximum blockage for about 40 min). The magnitude and duration of N-methyl-D-aspartate-produced biphasic effects on tail-flick latency were similar in awake and lightly pentobarbital-anesthetized rats, but caudally directed biting and scratching behavior was not produced in lightly anesthetized rats. Reversible spinalization at T8-T10 in lightly anesthetized rats (produced by cold-block) completely abolished inhibition of the tail-flick reflex produced by 1 nmol N-methyl-D-aspartate whereas facilitation produced by 10 pmol N-methyl-D-aspartate remained unchanged, indicating that N-methyl-D-aspartate-produced facilitation is a local, segmental effect and that N-methyl-D-aspartate-produced inhibition requires a supraspinal loop. To examine the nature of the supraspinal loop, potential contributions of descending noradrenergic and serotonergic systems were studied. Intrathecal pretreatment with 100 nmol phentolamine completely blocked N-methyl-D-aspartate-produced inhibition of the tail-flick reflex, while N-methyl-D-aspartate-produced facilitation and caudally directed biting and scratching behavior remained unchanged. Intrathecal pretreatment with 50 nmol methysergide reversed the inhibitory effect of 1 nmol N-methyl-D-aspartate, resulting in a potent and prolonged facilitation which could be blocked by D-2-amino-5-phosphonovaleric acid. (1 pmol). Intrathecal pretreatment with an alternate substrate for nitric oxide synthase, NG-nitro-L-arginine methyl ester (100 nmol), completely blocked N-methyl-D-aspartate-produced facilitation of the tail-flick reflex, whereas N-methyl-D-aspartate-produced inhibition and caudally directed biting and scratching behavior were unaffected.(ABSTRACT TRUNCATED AT 400 WORDS)
在清醒大鼠中研究了N-甲基-D-天冬氨酸（100 amol - 1 nmol）对伤害性甩尾反射的影响。鞘内注射较小剂量的N-甲基-D-天冬氨酸（100 amol - 10 pmol）至腰段脊髓，可产生剂量依赖性的甩尾反射易化作用（在0.5 - 1分钟时达到最大值）。所测试的最大剂量（1 nmol）抑制甩尾反射（在2 - 5分钟时达到最大值），并产生尾向搔抓和咬的行为，伴有鸣叫。用N-甲基-D-天冬氨酸受体拮抗剂D-2-氨基-5-磷酸戊酸（1 fmol - 1 pmol）进行鞘内预处理，该预处理对基线甩尾潜伏期无影响，以剂量依赖性方式阻断了所有N-甲基-D-天冬氨酸产生的效应（100 fmol D-2-氨基-5-磷酸戊酸产生约40分钟的最大阻断作用）。N-甲基-D-天冬氨酸对甩尾潜伏期产生的双相效应的幅度和持续时间在清醒和轻度戊巴比妥麻醉的大鼠中相似，但轻度麻醉的大鼠未产生尾向咬和搔抓行为。轻度麻醉大鼠（通过冷阻断产生）在T8 - T10处进行可逆性脊髓横断，完全消除了1 nmol N-甲基-D-天冬氨酸对甩尾反射的抑制作用，而10 pmol N-甲基-D-天冬氨酸产生的易化作用保持不变，表明N-甲基-D-天冬氨酸产生的易化作用是局部节段性效应，而N-甲基-D-天冬氨酸产生的抑制作用需要一个脊髓上环路。为了研究脊髓上环路的性质，研究了下行去甲肾上腺素能和5-羟色胺能系统的潜在作用。用100 nmol酚妥拉明进行鞘内预处理，完全阻断了N-甲基-D-天冬氨酸对甩尾反射的抑制作用，而N-甲基-D-天冬氨酸产生的易化作用以及尾向咬和搔抓行为保持不变。用50 nmol麦角新碱进行鞘内预处理，逆转了1 nmol N-甲基-D-天冬氨酸的抑制作用，导致一种强效且持久的易化作用，该作用可被D-2-氨基-5-磷酸戊酸（1 pmol）阻断。用一氧化氮合酶的替代底物NG-硝基-L-精氨酸甲酯（100 nmol）进行鞘内预处理，完全阻断了N-甲基-D-天冬氨酸对甩尾反射的易化作用，而N-甲基-D-天冬氨酸产生的抑制作用以及尾向咬和搔抓行为未受影响。（摘要截短至400字）
