Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados (Cinvestav), Sede Sur, México, D.F., Mexico.
Eur J Pain. 2013 Oct;17(9):1365-73. doi: 10.1002/j.1532-2149.2013.00305.x. Epub 2013 Mar 25.
l-Kynurenine has antinociceptive effects in acute and inflammatory pain. This study determined the effect of l-kynurenine and its metabolite (kynurenic acid) on rats subjected to neuropathic pain.
L5/L6 spinal nerve ligation induced tactile allodynia as measured with von Frey filaments using the up-down method. High-performance liquid chromatography and Western blot analysis determined kynurenic acid levels and expression of kynurenine amino transferase II (KAT II), respectively.
l-Kynurenine (50-200 mg/kg, i.p.) or probenecid (100 mg/kg, i.p.) did not affect allodynia in neuropathic rats. In contrast, l-kynurenine (50-200 mg/kg, i.p.) in combination with probenecid (100 mg/kg, i.p.), an inhibitor of organic anion transport, reversed allodynia. Furthermore, intrathecal kynurenic acid (1-30 μg) reversed allodynia. Probenecid (100 mg/kg, i.p.) supplementation enhanced the maximal antiallodynic effect of intrathecal kynurenic acid (10 μg). Only the combined administration of l-kynurenine (200 mg/kg)/probenecid (100 mg/kg) increased the kynurenic acid concentration in cerebrospinal fluid. KAT II is expressed in dorsal root ganglia and dorsal spinal cord. KAT II expression was unchanged by the spinal nerve ligation or l-kynurenine/probenecid combination. The kynurenine/probenecid combination did not affect motor activity.
l-Kynurenine produces its antiallodynic effect in the central nervous system through kynurenic acid. This effect may result from blockade of N-methyl-d-aspartate receptors. KAT II is expressed in dorsal root ganglion and dorsal spinal cord. Combined l-kynurenine and probenecid therapy has the potential to reduce neuropathic pain in humans.
L-犬尿氨酸在急性和炎症性疼痛中具有镇痛作用。本研究旨在确定 L-犬尿氨酸及其代谢产物（犬尿喹啉酸）对神经病理性疼痛大鼠的影响。
采用 von Frey 纤维丝法通过上下法测定 L5/L6 脊神经结扎引起的触诱发痛。高效液相色谱和 Western blot 分析分别测定犬尿喹啉酸水平和犬尿氨酸氨基转移酶 II（KAT II）的表达。
L-犬尿氨酸（50-200mg/kg，腹腔注射）或丙磺舒（100mg/kg，腹腔注射）均不影响神经病理性大鼠的触诱发痛。相反，L-犬尿氨酸（50-200mg/kg，腹腔注射）与丙磺舒（100mg/kg，腹腔注射）联合使用，一种有机阴离子转运抑制剂，可逆转触诱发痛。此外，鞘内给予犬尿喹啉酸（1-30μg）可逆转触诱发痛。丙磺舒（100mg/kg，腹腔注射）可增强鞘内犬尿喹啉酸（10μg）的最大抗触诱发痛作用。只有 L-犬尿氨酸（200mg/kg）/丙磺舒（100mg/kg）联合给药才能增加脑脊液中犬尿喹啉酸的浓度。KAT II 在背根神经节和背侧脊髓中表达。脊神经结扎或 L-犬尿氨酸/丙磺舒联合给药均不改变 KAT II 的表达。犬尿氨酸/丙磺舒联合用药不影响运动活动。
L-犬尿氨酸通过犬尿喹啉酸在中枢神经系统中产生镇痛作用。这种作用可能是由于阻断 N-甲基-D-天冬氨酸受体所致。KAT II 在背根神经节和背侧脊髓中表达。联合使用 L-犬尿氨酸和丙磺舒治疗有可能减轻人类的神经病理性疼痛。
