CB2受体激动剂JWH015对大鼠神经病理性疼痛的治疗作用

Objective To test whether activation of CB2 receptor would induce antinociception and investigate the role of in-trathecal JWH015 in the modulation of Tyr-1472 phosphorylation of the spinal NR2B subunit in a model of neuropathic pain. Meth-otis 84 male SD rats with intrathecal catheter insertion were randomly divided into 3 groups: sham + 50% DMSO group (Sham group); CCD + 50%DMSO group(Vehicle group); CCD+JWH015 group(JWH015 group). Seven days after Sham or CCD(without in-trathecal injection), the lumbosacral spinal cords of 6 Sham rats and 6 CCD rats were collected for immunohistochemical study to de-termine the spinal expression of Tyr-1472 phosphorylated NR2B subunit(baseline). The rest were intrathcally injected with 50%DMSO 10 μl or JWH015 10 μg seven days after Sham or CCD. For behavioral studies, the data of paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL) were measured in Sham group or CCD group, before intrathecal injection and 1, 2, 4, 8, 24, 72 h after intrathecal injection (n=6). For immunohistochemical study, the lumbosacral spinal cords were collected 4, 8, 24, 72 h after intrathecal injection(n=6). Results Compared with the baseline before operation, the PWMT and the PWTL of Vehicle group and JWHOI5 group began to decrease before intrathecal injection(P<0.01). Compared with Vehicle group, PWMT and PWTL of JWH015 group increased markedly 1, 2 and 4 h after intrathecal injection (P0.05). Tyr-1472 phosphorylated NR2B subunit expression in the superficial dorsal horn was weak in all sham groups, but increased significantly 7 days after CCD. While intrathecal 50%DMSO did not decrease the expres-sion of Tyr-1472 phosphorylated NR2B subunit in the superficial dorsal horn, the expression of Tyr-1472 phosphorylated NR2B sub-unit in the superficial dorsal horn decreased obviously 4 h and 8 h after intrathcal JWH015. However, the expression of Tyr-1472 phosphorylated NR2B subunit in the superficial dorsal horn increased again 24 h and 72 h after intrathcal JWH015. Conclusion In-trathecal administration of CB2 receptor agonist JWHOI5 may provide analgesic effect, which is probably attributed to the decrease in the spinal expression of Tyr-1472 phosphorylated NR2B subunit.     

CB2受体激动剂JWH015对大鼠神经病理性疼痛的治疗作用

Objective To test whether activation of CB2 receptor would induce antinociception and investigate the role of in-trathecal JWH015 in the modulation of Tyr-1472 phosphorylation of the spinal NR2B subunit in a model of neuropathic pain. Meth-otis 84 male SD rats with intrathecal catheter insertion were randomly divided into 3 groups: sham + 50% DMSO group (Sham group); CCD + 50%DMSO group(Vehicle group); CCD+JWH015 group(JWH015 group). Seven days after Sham or CCD(without in-trathecal injection), the lumbosacral spinal cords of 6 Sham rats and 6 CCD rats were collected for immunohistochemical study to de-termine the spinal expression of Tyr-1472 phosphorylated NR2B subunit(baseline). The rest were intrathcally injected with 50%DMSO 10 μl or JWH015 10 μg seven days after Sham or CCD. For behavioral studies, the data of paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL) were measured in Sham group or CCD group, before intrathecal injection and 1, 2, 4, 8, 24, 72 h after intrathecal injection (n=6). For immunohistochemical study, the lumbosacral spinal cords were collected 4, 8, 24, 72 h after intrathecal injection(n=6). Results Compared with the baseline before operation, the PWMT and the PWTL of Vehicle group and JWHOI5 group began to decrease before intrathecal injection(P<0.01). Compared with Vehicle group, PWMT and PWTL of JWH015 group increased markedly 1, 2 and 4 h after intrathecal injection (P0.05). Tyr-1472 phosphorylated NR2B subunit expression in the superficial dorsal horn was weak in all sham groups, but increased significantly 7 days after CCD. While intrathecal 50%DMSO did not decrease the expres-sion of Tyr-1472 phosphorylated NR2B subunit in the superficial dorsal horn, the expression of Tyr-1472 phosphorylated NR2B sub-unit in the superficial dorsal horn decreased obviously 4 h and 8 h after intrathcal JWH015. However, the expression of Tyr-1472 phosphorylated NR2B subunit in the superficial dorsal horn increased again 24 h and 72 h after intrathcal JWH015. Conclusion In-trathecal administration of CB2 receptor agonist JWHOI5 may provide analgesic effect, which is probably attributed to the decrease in the spinal expression of Tyr-1472 phosphorylated NR2B subunit.     

CB2受体激动剂JWH015对大鼠神经病理性疼痛的治疗作用

Objective To test whether activation of CB2 receptor would induce antinociception and investigate the role of in-trathecal JWH015 in the modulation of Tyr-1472 phosphorylation of the spinal NR2B subunit in a model of neuropathic pain. Meth-otis 84 male SD rats with intrathecal catheter insertion were randomly divided into 3 groups: sham + 50% DMSO group (Sham group); CCD + 50%DMSO group(Vehicle group); CCD+JWH015 group(JWH015 group). Seven days after Sham or CCD(without in-trathecal injection), the lumbosacral spinal cords of 6 Sham rats and 6 CCD rats were collected for immunohistochemical study to de-termine the spinal expression of Tyr-1472 phosphorylated NR2B subunit(baseline). The rest were intrathcally injected with 50%DMSO 10 μl or JWH015 10 μg seven days after Sham or CCD. For behavioral studies, the data of paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL) were measured in Sham group or CCD group, before intrathecal injection and 1, 2, 4, 8, 24, 72 h after intrathecal injection (n=6). For immunohistochemical study, the lumbosacral spinal cords were collected 4, 8, 24, 72 h after intrathecal injection(n=6). Results Compared with the baseline before operation, the PWMT and the PWTL of Vehicle group and JWHOI5 group began to decrease before intrathecal injection(P<0.01). Compared with Vehicle group, PWMT and PWTL of JWH015 group increased markedly 1, 2 and 4 h after intrathecal injection (P0.05). Tyr-1472 phosphorylated NR2B subunit expression in the superficial dorsal horn was weak in all sham groups, but increased significantly 7 days after CCD. While intrathecal 50%DMSO did not decrease the expres-sion of Tyr-1472 phosphorylated NR2B subunit in the superficial dorsal horn, the expression of Tyr-1472 phosphorylated NR2B sub-unit in the superficial dorsal horn decreased obviously 4 h and 8 h after intrathcal JWH015. However, the expression of Tyr-1472 phosphorylated NR2B subunit in the superficial dorsal horn increased again 24 h and 72 h after intrathcal JWH015. Conclusion In-trathecal administration of CB2 receptor agonist JWHOI5 may provide analgesic effect, which is probably attributed to the decrease in the spinal expression of Tyr-1472 phosphorylated NR2B subunit.     

CB2受体激动剂JWH015对大鼠神经病理性疼痛的治疗作用

Objective To test whether activation of CB2 receptor would induce antinociception and investigate the role of in-trathecal JWH015 in the modulation of Tyr-1472 phosphorylation of the spinal NR2B subunit in a model of neuropathic pain. Meth-otis 84 male SD rats with intrathecal catheter insertion were randomly divided into 3 groups: sham + 50% DMSO group (Sham group); CCD + 50%DMSO group(Vehicle group); CCD+JWH015 group(JWH015 group). Seven days after Sham or CCD(without in-trathecal injection), the lumbosacral spinal cords of 6 Sham rats and 6 CCD rats were collected for immunohistochemical study to de-termine the spinal expression of Tyr-1472 phosphorylated NR2B subunit(baseline). The rest were intrathcally injected with 50%DMSO 10 μl or JWH015 10 μg seven days after Sham or CCD. For behavioral studies, the data of paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL) were measured in Sham group or CCD group, before intrathecal injection and 1, 2, 4, 8, 24, 72 h after intrathecal injection (n=6). For immunohistochemical study, the lumbosacral spinal cords were collected 4, 8, 24, 72 h after intrathecal injection(n=6). Results Compared with the baseline before operation, the PWMT and the PWTL of Vehicle group and JWHOI5 group began to decrease before intrathecal injection(P<0.01). Compared with Vehicle group, PWMT and PWTL of JWH015 group increased markedly 1, 2 and 4 h after intrathecal injection (P0.05). Tyr-1472 phosphorylated NR2B subunit expression in the superficial dorsal horn was weak in all sham groups, but increased significantly 7 days after CCD. While intrathecal 50%DMSO did not decrease the expres-sion of Tyr-1472 phosphorylated NR2B subunit in the superficial dorsal horn, the expression of Tyr-1472 phosphorylated NR2B sub-unit in the superficial dorsal horn decreased obviously 4 h and 8 h after intrathcal JWH015. However, the expression of Tyr-1472 phosphorylated NR2B subunit in the superficial dorsal horn increased again 24 h and 72 h after intrathcal JWH015. Conclusion In-trathecal administration of CB2 receptor agonist JWHOI5 may provide analgesic effect, which is probably attributed to the decrease in the spinal expression of Tyr-1472 phosphorylated NR2B subunit.     

CB2受体激动剂JWH015对大鼠神经病理性疼痛的治疗作用

Objective To test whether activation of CB2 receptor would induce antinociception and investigate the role of in-trathecal JWH015 in the modulation of Tyr-1472 phosphorylation of the spinal NR2B subunit in a model of neuropathic pain. Meth-otis 84 male SD rats with intrathecal catheter insertion were randomly divided into 3 groups: sham + 50% DMSO group (Sham group); CCD + 50%DMSO group(Vehicle group); CCD+JWH015 group(JWH015 group). Seven days after Sham or CCD(without in-trathecal injection), the lumbosacral spinal cords of 6 Sham rats and 6 CCD rats were collected for immunohistochemical study to de-termine the spinal expression of Tyr-1472 phosphorylated NR2B subunit(baseline). The rest were intrathcally injected with 50%DMSO 10 μl or JWH015 10 μg seven days after Sham or CCD. For behavioral studies, the data of paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL) were measured in Sham group or CCD group, before intrathecal injection and 1, 2, 4, 8, 24, 72 h after intrathecal injection (n=6). For immunohistochemical study, the lumbosacral spinal cords were collected 4, 8, 24, 72 h after intrathecal injection(n=6). Results Compared with the baseline before operation, the PWMT and the PWTL of Vehicle group and JWHOI5 group began to decrease before intrathecal injection(P<0.01). Compared with Vehicle group, PWMT and PWTL of JWH015 group increased markedly 1, 2 and 4 h after intrathecal injection (P0.05). Tyr-1472 phosphorylated NR2B subunit expression in the superficial dorsal horn was weak in all sham groups, but increased significantly 7 days after CCD. While intrathecal 50%DMSO did not decrease the expres-sion of Tyr-1472 phosphorylated NR2B subunit in the superficial dorsal horn, the expression of Tyr-1472 phosphorylated NR2B sub-unit in the superficial dorsal horn decreased obviously 4 h and 8 h after intrathcal JWH015. However, the expression of Tyr-1472 phosphorylated NR2B subunit in the superficial dorsal horn increased again 24 h and 72 h after intrathcal JWH015. Conclusion In-trathecal administration of CB2 receptor agonist JWHOI5 may provide analgesic effect, which is probably attributed to the decrease in the spinal expression of Tyr-1472 phosphorylated NR2B subunit.     

CB2受体激动剂JWH015对大鼠神经病理性疼痛的治疗作用

Objective To test whether activation of CB2 receptor would induce antinociception and investigate the role of in-trathecal JWH015 in the modulation of Tyr-1472 phosphorylation of the spinal NR2B subunit in a model of neuropathic pain. Meth-otis 84 male SD rats with intrathecal catheter insertion were randomly divided into 3 groups: sham + 50% DMSO group (Sham group); CCD + 50%DMSO group(Vehicle group); CCD+JWH015 group(JWH015 group). Seven days after Sham or CCD(without in-trathecal injection), the lumbosacral spinal cords of 6 Sham rats and 6 CCD rats were collected for immunohistochemical study to de-termine the spinal expression of Tyr-1472 phosphorylated NR2B subunit(baseline). The rest were intrathcally injected with 50%DMSO 10 μl or JWH015 10 μg seven days after Sham or CCD. For behavioral studies, the data of paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL) were measured in Sham group or CCD group, before intrathecal injection and 1, 2, 4, 8, 24, 72 h after intrathecal injection (n=6). For immunohistochemical study, the lumbosacral spinal cords were collected 4, 8, 24, 72 h after intrathecal injection(n=6). Results Compared with the baseline before operation, the PWMT and the PWTL of Vehicle group and JWHOI5 group began to decrease before intrathecal injection(P<0.01). Compared with Vehicle group, PWMT and PWTL of JWH015 group increased markedly 1, 2 and 4 h after intrathecal injection (P0.05). Tyr-1472 phosphorylated NR2B subunit expression in the superficial dorsal horn was weak in all sham groups, but increased significantly 7 days after CCD. While intrathecal 50%DMSO did not decrease the expres-sion of Tyr-1472 phosphorylated NR2B subunit in the superficial dorsal horn, the expression of Tyr-1472 phosphorylated NR2B sub-unit in the superficial dorsal horn decreased obviously 4 h and 8 h after intrathcal JWH015. However, the expression of Tyr-1472 phosphorylated NR2B subunit in the superficial dorsal horn increased again 24 h and 72 h after intrathcal JWH015. Conclusion In-trathecal administration of CB2 receptor agonist JWHOI5 may provide analgesic effect, which is probably attributed to the decrease in the spinal expression of Tyr-1472 phosphorylated NR2B subunit.     

CB2受体激动剂JWH015对大鼠神经病理性疼痛的治疗作用

Objective To test whether activation of CB2 receptor would induce antinociception and investigate the role of in-trathecal JWH015 in the modulation of Tyr-1472 phosphorylation of the spinal NR2B subunit in a model of neuropathic pain. Meth-otis 84 male SD rats with intrathecal catheter insertion were randomly divided into 3 groups: sham + 50% DMSO group (Sham group); CCD + 50%DMSO group(Vehicle group); CCD+JWH015 group(JWH015 group). Seven days after Sham or CCD(without in-trathecal injection), the lumbosacral spinal cords of 6 Sham rats and 6 CCD rats were collected for immunohistochemical study to de-termine the spinal expression of Tyr-1472 phosphorylated NR2B subunit(baseline). The rest were intrathcally injected with 50%DMSO 10 μl or JWH015 10 μg seven days after Sham or CCD. For behavioral studies, the data of paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL) were measured in Sham group or CCD group, before intrathecal injection and 1, 2, 4, 8, 24, 72 h after intrathecal injection (n=6). For immunohistochemical study, the lumbosacral spinal cords were collected 4, 8, 24, 72 h after intrathecal injection(n=6). Results Compared with the baseline before operation, the PWMT and the PWTL of Vehicle group and JWHOI5 group began to decrease before intrathecal injection(P<0.01). Compared with Vehicle group, PWMT and PWTL of JWH015 group increased markedly 1, 2 and 4 h after intrathecal injection (P0.05). Tyr-1472 phosphorylated NR2B subunit expression in the superficial dorsal horn was weak in all sham groups, but increased significantly 7 days after CCD. While intrathecal 50%DMSO did not decrease the expres-sion of Tyr-1472 phosphorylated NR2B subunit in the superficial dorsal horn, the expression of Tyr-1472 phosphorylated NR2B sub-unit in the superficial dorsal horn decreased obviously 4 h and 8 h after intrathcal JWH015. However, the expression of Tyr-1472 phosphorylated NR2B subunit in the superficial dorsal horn increased again 24 h and 72 h after intrathcal JWH015. Conclusion In-trathecal administration of CB2 receptor agonist JWHOI5 may provide analgesic effect, which is probably attributed to the decrease in the spinal expression of Tyr-1472 phosphorylated NR2B subunit.     

CB2受体激动剂JWH015对大鼠神经病理性疼痛的治疗作用

Objective To test whether activation of CB2 receptor would induce antinociception and investigate the role of in-trathecal JWH015 in the modulation of Tyr-1472 phosphorylation of the spinal NR2B subunit in a model of neuropathic pain. Meth-otis 84 male SD rats with intrathecal catheter insertion were randomly divided into 3 groups: sham + 50% DMSO group (Sham group); CCD + 50%DMSO group(Vehicle group); CCD+JWH015 group(JWH015 group). Seven days after Sham or CCD(without in-trathecal injection), the lumbosacral spinal cords of 6 Sham rats and 6 CCD rats were collected for immunohistochemical study to de-termine the spinal expression of Tyr-1472 phosphorylated NR2B subunit(baseline). The rest were intrathcally injected with 50%DMSO 10 μl or JWH015 10 μg seven days after Sham or CCD. For behavioral studies, the data of paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL) were measured in Sham group or CCD group, before intrathecal injection and 1, 2, 4, 8, 24, 72 h after intrathecal injection (n=6). For immunohistochemical study, the lumbosacral spinal cords were collected 4, 8, 24, 72 h after intrathecal injection(n=6). Results Compared with the baseline before operation, the PWMT and the PWTL of Vehicle group and JWHOI5 group began to decrease before intrathecal injection(P<0.01). Compared with Vehicle group, PWMT and PWTL of JWH015 group increased markedly 1, 2 and 4 h after intrathecal injection (P0.05). Tyr-1472 phosphorylated NR2B subunit expression in the superficial dorsal horn was weak in all sham groups, but increased significantly 7 days after CCD. While intrathecal 50%DMSO did not decrease the expres-sion of Tyr-1472 phosphorylated NR2B subunit in the superficial dorsal horn, the expression of Tyr-1472 phosphorylated NR2B sub-unit in the superficial dorsal horn decreased obviously 4 h and 8 h after intrathcal JWH015. However, the expression of Tyr-1472 phosphorylated NR2B subunit in the superficial dorsal horn increased again 24 h and 72 h after intrathcal JWH015. Conclusion In-trathecal administration of CB2 receptor agonist JWHOI5 may provide analgesic effect, which is probably attributed to the decrease in the spinal expression of Tyr-1472 phosphorylated NR2B subunit.     

CB2受体激动剂JWH015对大鼠神经病理性疼痛的治疗作用

Objective To test whether activation of CB2 receptor would induce antinociception and investigate the role of in-trathecal JWH015 in the modulation of Tyr-1472 phosphorylation of the spinal NR2B subunit in a model of neuropathic pain. Meth-otis 84 male SD rats with intrathecal catheter insertion were randomly divided into 3 groups: sham + 50% DMSO group (Sham group); CCD + 50%DMSO group(Vehicle group); CCD+JWH015 group(JWH015 group). Seven days after Sham or CCD(without in-trathecal injection), the lumbosacral spinal cords of 6 Sham rats and 6 CCD rats were collected for immunohistochemical study to de-termine the spinal expression of Tyr-1472 phosphorylated NR2B subunit(baseline). The rest were intrathcally injected with 50%DMSO 10 μl or JWH015 10 μg seven days after Sham or CCD. For behavioral studies, the data of paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL) were measured in Sham group or CCD group, before intrathecal injection and 1, 2, 4, 8, 24, 72 h after intrathecal injection (n=6). For immunohistochemical study, the lumbosacral spinal cords were collected 4, 8, 24, 72 h after intrathecal injection(n=6). Results Compared with the baseline before operation, the PWMT and the PWTL of Vehicle group and JWHOI5 group began to decrease before intrathecal injection(P<0.01). Compared with Vehicle group, PWMT and PWTL of JWH015 group increased markedly 1, 2 and 4 h after intrathecal injection (P0.05). Tyr-1472 phosphorylated NR2B subunit expression in the superficial dorsal horn was weak in all sham groups, but increased significantly 7 days after CCD. While intrathecal 50%DMSO did not decrease the expres-sion of Tyr-1472 phosphorylated NR2B subunit in the superficial dorsal horn, the expression of Tyr-1472 phosphorylated NR2B sub-unit in the superficial dorsal horn decreased obviously 4 h and 8 h after intrathcal JWH015. However, the expression of Tyr-1472 phosphorylated NR2B subunit in the superficial dorsal horn increased again 24 h and 72 h after intrathcal JWH015. Conclusion In-trathecal administration of CB2 receptor agonist JWHOI5 may provide analgesic effect, which is probably attributed to the decrease in the spinal expression of Tyr-1472 phosphorylated NR2B subunit.     

鞘内注射Roscovitine缓解大鼠慢性神经病理性疼痛

目的 在SD大鼠脊髓后根神经节慢性压迫(CCD)模型上观察鞘内注射Roscovitine的镇痛效果.方法 用不锈钢棒(长4 mm,直径0.7 mm)持续件压迫脊髓背根神经节(DRG)建立慢性神经病理性疼痛模型.术后第7天鞘内注射溶解于DMSO 10 μl中的Roscovitine 50 μg(R组);同时设CCD术后第7天只给予鞘内注射二甲基亚砜(DMS0)10 μl的CCD组(C组)和非CCD处理、并给予鞘内注射DMSO 10 μl的假手术组(S组).三组均于CCD术前、术后第7天(给药前)及给药后2、24、72 h榆测机械痛缩足阈值(PWMT)和热痛缩足潜伏期(PWTL).CCD术前及给药后72 h用免疫组化技术检测脊髓背角N-甲基-D天冬门氨酸(NMDA)受体2A亚基(NR2A)的表达水平.结果 R组和C组给药前PWMT均较术前显著降低[(3.64±0.40)g vs.(14.38±1.53)g,(3.50±0.77)g vs(13.25±2.21)g],也明显低于S组的(11.31±1.13)g(P<0.05).R组和C组给药前PWTL均较术前显著缩短[(9.28±1.18)s vs(18.34±1.23)s,(8.91±1.08)s vs.(18.59±1.92)s],也短于S组的(18.45±1.44)s(P<0.05).R组PWMT在给药后24 h较给药前和C组显著增加[(7.32±0.69)g vs.(3.64±0.40)g,(3.86±1.14)g](P<0.05),而给药后2 h PWTL,较给药前和C组显著延长[(15.464±1.51)s vs.(9.28±1.18)s,(9.91±1.07)s(P<0.05).给药后72 h,R组脊髓背角NR2A受体表达水平明显低于C组[(0.21±0.02)vs.(0.26±0.01)](P<0.05).结论 鞘内注射Roseovitine能有效改善CCD大鼠痛行为学反应;其作用可能与抑制脊髓背角NR2A受体表达有关.     

鞘内注射细胞周期素依赖性激酶-5抑制剂Roscovitine对慢性背根节压迫大鼠痛行为学的影响

目的 探讨鞘内注射细胞周期素依赖性激酶-5(Cdk5)抑制剂Roscovitine对慢性背根节压迫(CCD)大鼠痛行为学的影响.方法 雄性SD大鼠24只随机分为4组,每组6只:假手术组+50%二甲基亚砜(S组);CCD+50%二甲基哑砜(C组):CCD+Roscovitine 50μg(R组);CCD0组(C0组)C0组不注入任何药物,只作为对照.各组大鼠在CCD或假手术后第7天分别鞘内注射容积为10μl的50%DMSO或Roscovitine 50μg,分别观察给药后的1、4、8 h大鼠机械缩爪阂值(paw withdrawal mechani-cal threshold,PWMT)和热缩爪潜伏期(paw withdrawal thermal latency,PWTL).结果 与基础值相比,除S组外,各组大鼠从术后开始PWMT和PWTL均明显降低(P＜0.05),R组给药后与C组相比PWMT在各时间点无明显改变,PWTL相比明显增加,且保持在较高水平(P＜0.05).结论 脊髓背角Cdk5参与神经病理性疼痛的信号转导过程.     

蛛网膜下腔注射Ro25-6981对切口痛大鼠的镇痛作用研究

目的 研究蛛网膜下腔注射Ro 25-6981,一种新型选择性的N-甲基-D-天门冬氨酸(NMDA)受体NR2B亚基拮抗剂,对切口痛大鼠的镇痛作用.方法 雄性SD大鼠60只,将大鼠采用随机数字表法分为4组,每组15只:对照组(C组)、切口痛组(Ⅰ组)、鞘内注射Ro 25-6981 50μg/25μl组(R1组)、鞘内注射Ro 25-6981 200μg/25μl组(R2组),每组15只.C组和Ⅰ组均鞘内注射5%DMSO溶剂25 μl.Ⅰ组、R1组和R2组在鞘内注射后行右后足切口痛模型制备.所有动物接受鞘内注射和手术均在吸入七氟醚麻醉下进行.术前24 h、术后2、6、24h检测大鼠痛行为学指标,包括50%机械缩足阈值(paw withdrawal mechanical threshold,PWMT)和热缩足反射潜伏期(paw withdrawal thermal latency,PWTL),同时测定鞘内给药前后大鼠的运动功能.结果 与C组和术前基础值比较,Ⅰ组术后各时间点50%PWMT(7.0±0.9)、(6.7±0.7)、(6.4±1.2)g和PWTL(10.3±1.4)、(10.1±1.0)、(10.0±1.0)s均降低(P＜0.05);与Ⅰ组比较,R1组各时间点50%PWMT和PWTL差异无统计学意义(P＞0.05);R2组术后2 h 50%PWMT(9.0±0.8)g和PWTL(13.7±1.0)s与Ⅰ组相比均升高(P＜0.05),6、24 h痛行为学差异无统计学意义;鞘内给药前后大鼠运动功能差异无统计学意义(P＞0.05).结论 鞘内注射选择性的Np2B拮抗剂Ro 25-6981 200.0μg可以对切口痛大鼠产生明显的镇痛作用而不影响运动功能.

Abstract：

Objective To investigate the analgesic effects of intrathecal administration of Ro 25-6981, a selective antagonist of the NR2B subunit of NMDA receptors (NR2B), in a rat model of incision pain. Methods Sixty SD rats were randomly divided into 4 groups: control group (C); incisional pain group (Ⅰ); intrathecal group of Ro 25-6981 at the dose of 50 μg/25 μl(R1);intrathecal group of Ro 25-6981 at the dose of 200 μg/25 μl(R2). Intrathecal injection of 5% DMSO solvent at the dose of 25 μl was administrated in group C and Ⅰ. Rat models of incisional pain on the right hind were prepared after intrathecal injection in group Ⅰ,R1 and R2. All rats were anesthetized with sevoflurane. The 50% paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL) were tested to evaluate the behavioral changes and measured at 24 h before incision and at 2,6,24 h after incision. And the locomotor functions were also examined at the same time points. Results Compared with group C and baseline,the decreases of 50% PWMT (7.0±0.9), (6.7±0.7), (6.4±1.2) g and PWTL (10.3±1.4), ( 10. 1±1.0), (10.0±1.0) s were observed at each time point after incision in group Ⅰ (P＜0.05); Compared with group Ⅰ, significant changes of 50% PWMT and PWTL were not observed at each time point in group R1 (P＞0.05); Compared with group Ⅰ, increases of both 50% PWMT (9.0±0.8) g and PWTL (13.7±1.0) s were observed at 2 h after incision in group R2 (P＜0.05), while no significant changes of 50% PWMT and PWTL were observed at 6 h and 24 h after incision in group R2. No significant changes in locomotor functions were observed before and after intrathecal administration in rats (P＞0.05). Conclusion Intrathecal injection of Ro 25-6981 at the dose of 200.0 μg, the selective antagonist of the NR2B, exerts significant analgesic effects on incision pain in rats without affecting of locomotor functions.     

鞘内注射地塞米松对背根节压迫大鼠镇痛作用的行为学观察

目的 在大鼠慢性背根神经节压迫模型中观察鞘内注射地塞米松的镇痛效果.方法 制作慢性背根神经节压迫模型(CCD组),同时制作不给予背根神经节压迫的假手术模(sham组).所有的实验大鼠在术前3d,术后第3、4、7、10、13、14、15天检测痛行为学指标.包括机械痛缩足阈值(paw withdrawal mechanical threshold,PWMT)和热痛缩足潜伏期(paw with-drawal themud latencv,PWTL).CCD模型组分为10%DWSO对照组(C组)、早期治疗组(ET组)、后期治疗组(LT组)和二次治疗组(TT组).10%DWSO对照组在术后第3天和第13大鞘内给予10%DWSO,早期治疗组于术后第3天分别给予地塞米松,第13天给予10%DWSO.后期治疗组于术后第3天给予10%DWSO,第13天给予地塞米松,二次治疗组术后第3、13天均给予地塞米松.结果 术后3 d空白对照组PWMT(2.67±1.03)较sham组PWMT(11.33±2.94)和术前基础值PWMT(13.33+2.58,13.33±2.58.13.33±2.58)有显著降低(P<0.05)、C组PWTL(8.82±1.82)较sham组(22.14±2.34)和基础值(22.52±1.94,21.59~2.49.22.46±1.52)明显缩短(P<0.05).鞘内给药之后ET组和TT组PWMT增高(P<0.05),PWTL延长(P<0.05);但LT组PWTL、PWMT无明显变化(P>O.05).结论 鞘内注射地塞米松可以有效改善慢性背根神经节压迫引起的痛行为学反应,但具有时间依赖性.     

鞘内注射Akt抑制剂Ⅳ对注射式根性神经痛大鼠痛行为学的影响

目的 探讨鞘内给予Akt抑制剂Ⅳ对注射式根性神经痛大鼠痛行为学的影响.方法 选择成功鞘内置管后无运动障碍的雄性SD大鼠18只,用分段随机分组法分为假手术组(S组)、溶剂对照组(C组)和Akt抑制剂组(A组),每组6只.C组和A组均采用注射surgiflo制备注射式根性神经痛模型,A组于造模前30 min给予Akt抑制剂...     

神经痛大鼠脊髓胶质细胞源性神经营养因子参与多巴胺D2受体激动剂对痛觉过敏的调制作用

目的 研究鞘内注射多巴胺D2受体激动剂喹吡罗对坐骨神经慢性压迫损伤大鼠脊髓水平胶质细胞源性神经营养因子表达的影响,探讨其介导抗伤害作用的可能机制. 方法 实验1：采用完全随机分组方法将30只成年雄性SD大鼠制作坐骨神经慢性压迫损伤（chronic constriction injury of sciatic nerve,CCI）模型分为5组（每组6只）：CCI＋生理盐水（NS组）、CCI＋喹吡罗0.1 μg（Q0.1组）、CCI＋喹吡罗1μg（Q1组）、CCI＋喹吡罗5 μg（Q5组）、CCI＋喹吡罗10 μg（Q10组）,分别在建模后第7天鞘内注射0.1、1、5、10 μg喹吡罗,NS组单次鞘内注射生理盐水10μl.于给药前及给药后0.5、1、2、4、8、16h测定大鼠术侧后足机械缩足反射阈值（paw withdrawal mechanical threshold,PWMT）和热缩足反射潜伏期（paw withdrawal thermal latency,PWTL）.实验2：将54只成年雄性SD大鼠制作CCI模型,并采用完全随机分组方法分为3组（Q5组、Q10组、NS组,每组18只）：Q5组、Q10组分别在建模后第7天鞘内注射5、10μg喹吡罗后0.5、1、2、4、8、16h处死取材,NS组单次鞘内注射生理盐水10μl;另取6只正常大鼠作为模型对照组（M组）,另取6只正常大鼠作为对照组（C组）.采用免疫印迹法测定脊髓背角胶质细胞源性神经营养因子（glial cell line-derived neurotrophic fact,GDNF）蛋白表达的变化. 结果 实验1：与NS组比较,Q0.1组注药后各时间点PWMT和PWTL差异无统计学意义（P＞0.05）,Q1组注药后2 h PWMT[（4.3±1.5）g]及PWTL[（13.2±1.6）s],Q5组注药后1,2、4 h PWMT[（4.7±1.6）、（5.3±1.6）、（4.7±2.1）g]和PWTL[（14.0±1.7）、（15.2±1.5）、（13.4±1.6）s],Q10组注药后1、2、4 h PWMT[（6.0±1.3）、（7.3±1.0）、（5.3±2.1）g]和PWTL [（15.3±1.8）、（17.5±1.2）、（14.9±1.7）s]明显升高（P＜0.05）.实验2：与C组比较,M组GDNF表达（0.95±0.09）明显升高（P＜0.05）.与M组和NS组比较,GDNF的表达Q     

大麻素受体2激动剂JWH-015对骨癌痛大鼠脊髓背角磷酸化环磷酸腺苷反应元件结合蛋白的影响

目的探讨腹腔注射大麻素受体（cannabinoid receptor,CB）2激动剂对骨癌痛大鼠脊髓背角磷酸化环磷酸腺苷反应元件结合蛋白（phosphorylated cyclic AMP respons eclement binding protein,pCREB）表达的影响。方法运用随机数字表法将63只雌性SD大鼠分为3组：肿瘤给药组（J组,15只）、肿瘤对照组（D组,24只）和假手术对照组（S组,24只）。J组、D组的大鼠左侧胫骨上端骨髓腔被注入5μl Walker256大鼠乳腺癌细胞制备骨癌痛模型;S组则注入等量的生理盐水。在造模后第10天,J组腹腔注射JWH-015（100μg/500μ1）,D组、s组注射等量JWH-015溶剂二甲基亚砜（dimethylsulfoxide,DMSO）。每组大鼠于造模前1d,造模后4、7、10d,腹腔注射后2、6、24、48、72h,检测手术侧机械刺激缩足阈值（paw withdrawal mechanical threshold,pwMT）和行走痛行为学评分。D组和S组大鼠于造模后4、7d,J组、D组和S组大鼠于造模后10d及腹腔注射后6、24、72h,取脊髓腰膨大进行免疫印迹分析。结果与S组比较,J组和D组大鼠造模后7d PWMT开始降低（P〈0.05）,造模后10d行走痛行为学评分增加（P〈0.05）,脊髓背角pCREB表达水平于7、10d上调（P〈0.05）.与D组比较,腹腔注射JWH-015后24h,J组PWMT（8.7±1.6）g显著上升（P〈0.05）,行走痛行为学评分（1.0±0.6）分和pCREB的表达（0.56±0.10）明显下降（P〈0.05）。结论腹腔注射JWH-015可能通过下调脊髓背角pCREB的表达改善骨癌痛大鼠的痛行为。     

鞘内注射艾芬地尔对骨癌痛小鼠脊髓NR2B mRNA表达的影响

目的 探讨鞘内注射艾芬地尔对骨癌痛小鼠脊髓N-甲基-D-天冬氨酸(NMDA)受体2B亚基(NR2B)mRNA表达的影响.方法 雄性C3H/HeJ小鼠140只,体重20～25 g,4～6周龄,随机分为5组(n=28):假手术组(S组)、骨癌病组(B组)和艾芬地尔2.5μg、5μg、10μg组(I1-3组).I1-3组和B组于小鼠右侧股骨远端骨髓腔接种NCTC 2472溶骨性纤维肉瘤细胞,建立骨癌痛模型;S组不接种肿瘤细胞.I1～3组于接种肿瘤细胞后14 d分别鞘内注射艾芬地尔2.5、5、10 μg,B组和S组鞘内注射艾芬地尔溶媒.各组于接种肿瘤细胞前1 d、鞘内注射艾芬地尔或溶媒前1 h、注射后2、12和24 h(T1～5)时随机取7只小鼠测定机械痛阈和热痛阈,并于T2～5,时测定后断头处死,取L3～5脊髓,采用RT-PCR法测定脊髓组织NR2B mRNA的表达水平.结果 与S组比较,除I3,组T3时热痛阈差异无统汁学意义(P0.05)外,B组和I1～3组机械痛阈和热痛阈均降低(P<0.05),B组和I1组脊髓组织NR2B mRNA表达上调,I2组该指标表达下调(P<0.05);与B组比较,I2.3组机械痈阈和热痛阈升高,脊髓组织NR2B mRNA表达下调(P<0.05),I1组各时点以上指标差异均无统计学意义(P0.05);与I2组比较,I3组机械痛阈和热痛阈升高,脊髓组织NR2B mRNA表达下调(P<0.05).结论 鞘内注射艾芬地尔可通过阻断含2B亚基的NMDA受体缓解小鼠骨癌痛,并下凋脊髓组织NR2B mRNA的表达抑制痛敏反应.     

二甲基亚砜抑制吗啡诱导热痛觉过敏的实验研究

【摘要】 目的 观察二甲基亚砜(DMSO)对吗啡诱导的热痛觉过敏及其对脊髓背角肿瘤坏死因子(TNF-α)表达的影响。方法 32只SD大鼠随机分为4组,A组(生理盐水+吗啡组)、B组(10%DMSO 5 mL/kg+吗啡组),C组(10%DMSO 5 mL/kg+生理盐水组)和D组(生理盐水组)。各组大鼠分别每d3PM腹腔注射生理盐水或DMSO,30 min后皮下注射吗啡或生理盐水。观察注药前1 d,注药后3 d、6 d、10 d大鼠热刺激撤足潜伏期的变化及脊髓背角TNF?鄄α表达情况。结果 与注药前相比,A组注药后3 d开始热刺激撤足潜伏期缩短,10 d进一步缩短(P<0.01)。与A组比较,B组注药后6 d、10 d热刺激撤足潜伏期延长有统计学意义(P<0.01)。A组脊髓背角TNF?鄄α表达较其它组增高(P<0.01)。B组TNF?鄄α的表达较A组低,较D组高有统计学意义(P<0.01)。结论 DMSO可能通过抑制脊髓背角TNF?鄄α的产生而减轻吗啡诱导的热痛觉过敏。     

脊髓水平神经型一氧化氮合酶在骨癌痛发生中的作用

目的 探讨脊髓水平神经型一氧化氮合酶(neuronal nitric oxide synthase,nNOS)在小鼠骨癌痛发生中的作用.方法 72只C3H/Hej小鼠随机分为肿瘤组(n=40只)和假手术组(n=32只).肿瘤组再分为5组(n=8):T7组(肿瘤细胞接种后7 d),T10组(接种后10 d)和T14组(接种后14 d),L组(接种后14 d+L-NMMA)和C组(接种后14 d+溶剂),假手术组相应分为s7组(假手术7 d)、S10组(假手术10 d)、S14组(假手术14 d)和S组(假手术14 d+溶剂).将含105个纤维肉瘤NCTC 2472细胞的最小必需培养基(α-MEM)注射到小鼠右侧股骨远端骨髓腔内,制作骨癌痛模型.假手术组注入不含肿瘤细胞的α-MEM.按照分组在相应时间点处死小鼠,用RT-PCR的方法检测脊髓腰膨大nNOS mRNA水平.术后14 d,L组小鼠鞘内注射NOS抑制剂L-NMMA 50μg,给药前及给药后2 h、12 h、24 h检测小鼠痛行为学的变化:机械痛缩足阈值(PWMT)和热痛缩足潜伏期(PWTL).结果 肿瘤细胞接种后10 d,脊髓水平nNOS mRNA表达较假手术组增高(P<0.05),而接种后14 d nNOS mRNA水平与假手术鼠无差别;鞘内注射L-NMMA 50 μg明显改善早期骨癌痛小鼠的痛行为.结论 脊髓水平nNOS可能在小鼠骨癌痛发生的早期起作用,而癌痛的维持依赖于其他类型一氧化氮合酶(nitric oxide synthase,NOS).     

脊髓背角卡配因在大鼠足底炎性痛形成中的作用

目的 探讨脊髓背角卡配因在大鼠足底炎性痛形成中的作用.方法 雄性SD大鼠48只,6周龄,体重160～200 g,采用随机数字表法,将其随机分为3组:正常对照组(C组,n=8)、PBS组(n=16)和酵母多糖诱发足底炎性痛组(Z组,n=24).Z组于大鼠左侧后足足底皮下注射酵母多糖1.25 mg,制备酵母多糖诱发足底炎性痛模型,PBS组给予等容量PBS 100μl.分别于给药前(T0)、给药后30 min(T1)、1 h(T2)、2 h(T3)、4 h(T4)、8 h(T5)、24 h(T6)和48 h(T7)时测定左侧后足机械刺激缩足阈值(MWT)、热缩足反应潜伏期(PWTL)和左侧后足足底最大厚度.PBS组于T4时处死8只大鼠,Z组分别于T4、T6和T7时各处死8只大鼠,取左侧脊髓L4～6节段,采用Western blot法测定脊髓背角spectrin αⅡ降解产物、IκBα、环氧化酶-2(COX-2)的表达和NF-κB活性.结果 与C组比较,Z组MWT降低,PWTL缩短,足底最大厚度增厚,脊髓背角spectrin αⅡ降解产物和COX-2的表达上调,IκBα表达下调,NF-κB活性升高(P＜0.05或0.01),PBS组上述指标差异无统计学意义(P＞0.05).结论 脊髓背角卡配因活化参与了大鼠足底炎性痛的形成,其机制与激活NF-κB,上调COX-2表达有关.