Prolonged suppression of plasma LH levels in male rats after a single injection of an LH-RH agonist in poly(DL-lactide-co-glycolide) microcapsules

The authors have examined the effects of a subcutaneous injection of the LH-RH agonist D-Trp6-LH-RH formulated in biodegradable poly(DL-lactide-co-glycolide) microcapsules on plasma levels of D-Trp6LH-RH, LH, and PRL in adult, gonadectomized male rats. Immunoreactive D-Trp6-LH-RH was detectable in the plasma of these animals at 1, 2, 3, and 4 weeks after injection. LH concentrations were greatly reduced 1 week after administering the D-Trp6-LH-RH microcapsule, continued to decrease during the following week, and remained suppressed until the end of the study, 6 weeks after the injection. Plasma PRL levels appeared elevated 1 to 2 weeks after the injection and suppressed thereafter, but these effects were significant only in animals rendered hyperprolactinemic by transplantation of an isologous pituitary under the renal capsule. These results demonstrate that an LH-RH agonist formulated in biodegradable microcapsules and administered as a subcutaneous injection can exert marked biologic effects in rats for at least 6 weeks. These findings also suggest that prolonged exposure to an LH-RH agonist may first produce stimulation, followed by an inhibition of PRL release from both in situ and ectopic pituitaries.     

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

目的 研究鞘内注射CB2受体激动剂JWH015对背根节慢性压迫(chronic compression of the dorsal root ganglia,CCD)大鼠痛阈和脊髓背角磷酸化NMDA受体NR2B亚基表达的影响,探讨CB2受体激动剂的镇痛作用及其可能机制.方法 鞘内置管成功后的雄性SD大鼠84只,随机分为3组:假手术+50%二甲基亚砜(dimethyl sulphoxide,DMSO)组(Sham组)、CCD+50%DMSO组(Vehicle组)、CCD+JWH015组(JWH015组).Sham组和Vehicle组各有6只大鼠在假手术或CCD后第7天(鞘内未给药)取脊髓标本,作为免疫组织化学法检测脊髓背角Tyr-1472磷酸化NR2B亚基表达的基础值.其余大鼠在假手术或CCD后第7天分别鞘内注射50%DMS010μl或JWH015 10μg.假手术或CCD之前、鞘内给药之前、之后1、2、4、8、24、72 h分别记录机械刺激缩足反射阈值(paw withdrawal mechanical threshold,PWMT)和热刺激缩足反射潜伏期(paw withdrawalthermal latency,PWTL)(n=6),鞘内给药之后4、8、24、72 h分别取脊髓标本(n=6),应用免疫组织化学法检测脊髓背角Tyr-1472磷酸化NR2B亚基的表达情况.结果 鞘内给药前Vehicle组和JWH015组大鼠的PWMT和PWTL均较基础值明显下降(P<0.01);与Vehicle组相比,JWH015组在给药后1、2、4 h PWMT和PWTL显著升高(P<0.01),但在给药后8、24、72 h差异无统计学意义(P>0.05);Sham组大鼠脊髓背角Tyr-1472磷酸化NR2B业基均呈低水平表达,但在CCD后第7天表达水平明显增强;鞘内注射50%DMSO后在各时间点均未能减弱CCD大鼠脊髓背角Tyr-1472磷酸化NR2B亚基的表达;鞘内注射JWH015在给药后4、8 h能明显减弱CCD大鼠脊髓背角Tyr-1472磷酸化NR2B亚基的表达,但在给药后24、72 h Tyr-1472磷酸化NR2B亚基的表达再次增强.结论 CB2受体激动剂JWH015对大鼠的神经病理性疼痛有治疗作用,该作用可能与抑制脊髓背角Tyr-1472磷酸化NR2B亚基的表达有关.     

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.     

大鼠鞘内注射曲马多的抗伤害性效应及与脊髓α2受体效应的关系

目的 探讨鞘内注射曲马多抗伤害性效应及与脊髓α_2受体效应的关系。方法 Wistar大鼠蛛网膜下腔埋管后随机分为5组(n=8):生理盐水对照组、曲马多10μg组、育亨宾10μg组、育亨宾1mμg+曲马多10μg组。育亨宾10μ+纳洛酮10μg+曲马多10μg组。于大鼠左后爪掌心皮下注射2.5％福尔马林50μl后鞘内注入上述药物,从福尔马林注射后的30min开始对大鼠的表现行为进行Dubuisson ＆ Dennis评分。另取一组大鼠断头处死后取腰段脊髓制成细胞膜悬液,以~3H-育亨宾为放射性标记配基,盐酸育亨宾为非标记配基,曲马多为竞争剂,行标记配基的饱和结合反应及竞争取代反应,并计算~3H-育亨宾与脊髓α_2受体结合的平衡解离常数(KD)及曲马多与~3H-育亨宾竞争结合脊髓α_2。受体的抑制常数(KI)。结果 鞘内注入10μg的曲马多能显著抑制福尔马林注射后大鼠的疼痛反应。10μg育亨宾单独鞘内注入无明显抗伤害性效应(P>0.05),预处理可使10μg曲马多鞘内注入后大鼠的伤害效应评分最多可增加56%,但仍低于对照组大鼠的伤害性效应评分(P<0.05);增加纳洛酮10μg预处理可使10μg曲马多鞘内注入后大鼠的伤害效应评分增加200％。受体放射性分析表明~3H-育亨宾的KD值为1.79nmol/L,曲马多的KI值为34.14μmol/L,IC_(50)为68.25μmol/L,提示曲马多与     

The antinociceptive effect of intrathecal tramadol in rats: the role of alpha 2-adrenoceptors in the spinal cord

Purposes  

The alpha 2 (α₂)-adrenoceptor is highly important in the antinociception of tramadol administered systemically and intrathecally. However, it is unclear whether tramadol at the spinal level exerts an antinociceptive effect by directly binding with α₂-adrenoceptors in the spinal cord. This study was conducted to investigate the relationship between α₂-adrenoceptors and the antinociception of tramadol at the spinal level.     

生物降解聚-DL-乳酸腰椎椎间融合器体内降解的生物力学研究

目的 探讨聚-DL-乳酸(poly DL-lactic acid,PDLLA)可降解腰椎椎间融合器在体内降解过程的生物力学变化规律,为进一步临床研究提供理论基础.方法 48头健康成年家猪随机分为实验组和对照组,分别在L4.5椎间隙植入填充自体骨的PDLLA可吸收腰椎椎间融合器或大小相当的自体骨块.分别在术后1、3、6、9、12及18个月处死动物取材.在脊柱三维运动试验机上模拟腰椎的三维运动进行屈伸、左右侧屈和左右轴向旋转运动,进行非破坏性生物力学测试来观察融合节段的稳定性.结果 1个月时两组在各个状态的运动范围差异均无统计学意义,术后3个月实验组的运动范围均大于对照组,但其差异除后伸状态外均无统计学意义.在术后6个月时实验组的测量结果 均大于对照组,此时二者在右旋最小,后伸最大,两组测量值只有在后伸状态差异有统计学意义.在术后9个月时测量结果 除左右旋转运动外实验组均高于对照组,此时仍是右旋最小,实验组后伸状态最大,对照组在右侧屈最大,但各状态数值相比差别趋于减小,此阶段只有后伸状态差异有统计学意义.术后12个月时只有后伸和左屈时实验组大于对照组,其余均小于对照组,两组相比后伸状态有统计学意义.术后18个月时两组各状态的运动范围相近.结论 PDLLA可降解腰椎椎间融合器植入体内前3个月为自身稳定期,3～6个月为易松动期,6～9个月处于稳定与非稳定之间的临界期,9～12个月进入稳定期,植入体内12～18个月达到骨融合期.     

Refractory status epilepticus after inadvertent intrathecal injection of tranexamic acid treated by magnesium sulfate

We present a case of accidental injection of tranexamic acid during spinal anesthesia for an elective cesarean delivery. Immediately following intrathecal injection of 2 mL of solution, the patient complained of severe back pain, followed by muscle spasm and tetany. As there was no evidence of spinal block, the medications given were checked and a ‘used’ ampoule of tranexamic acid was found on the spinal tray. General anesthesia was induced but muscle spasm and tetany persisted despite administration of a non-depolarizing muscle relaxant. Hemodynamic instability, ventricular tachycardia, and status epilepticus developed, which were refractory to phenytoin, diazepam, and infusions of thiopental, midazolam and amiodarone. Magnesium sulfate was administered postoperatively in the intensive care unit, following which the frequency of seizures decreased, eventually stopping. Unfortunately, on postoperative day three the patient died from cardiopulmonary arrest after an oxygen supply failure that was not associated with the initial event. This report underlines the importance of double-checking medications before injection in order to avoid a drug error. As well, it suggests that magnesium sulfate may be useful in stopping seizures caused by the intrathecal injection of tranexamic acid.     

An assessment of the antinociceptive efficacy of intrathecal and epidural contulakin-G in rats and dogs

Contulakin-G is a novel conopeptide with an incompletely defined mechanism of action. To assess nociceptive activity we delivered Contulakin-G as a bolus intrathecally (0.03, 0.1, 0.3, 3 nmol) or epidurally (10, 30, 89 nmol) in rats. Intrathecal Contulakin G significantly decreased Phase II and, to a lesser degree, Phase I paw flinching produced by intradermal formalin. Intrathecal and epidural doses of ED50s were 0.07 nmol and 45 nmol, respectively, giving an epidural/intrathecal ED50 ratio = 647). In dogs, intrathecal Contulakin-G (50-500 nmoL) produced a dose-dependent increase in the thermally evoked skin twitch latency by 30 min after administration, as did morphine (150 and 450 nmol). Epidural morphine (750 and 7500 nmol), but not epidural 1000 nmol Contulakin-G, also significantly decreased skin twitch in dogs. No changes in motor function were seen in any rats or dogs receiving these doses of Contulakin-G. In dogs, no physiologically significant dose-dependent changes in motor function, heart rate, arterial blood pressure, or body temperature were found. Contulakin-G is a potent antinociceptive drug when delivered intrathecally with no observable negative side effects in rats or dogs and may provide an alternative to opioid spinal analgesics.     

The effect of antinociceptive drugs tested at different times after nerve injury in rats

Given the evolving nature of anatomical and functional changes in the nervous system that are involved in the development of neuropathic pain, it is possible that the differing time course after injury underlies the inconsistent efficacy of drugs in neuropathic pain patients. In the current study, we evaluated the behavioral effects of two standard drugs used clinically for neuropathic pain, the anticonvulsant gabapentin and antidepressant imipramine, in rats at different times after peripheral nerve injury. Rats that underwent the spared nerve injury procedure responded to an innocuous mechanical stimulus (von Frey filament) 2, 4, and 8 wk after injury. Gabapentin dose-dependently suppressed mechanical sensitivity at all time points tested but the potency of gabapentin was three-fold less 4 wk postinjury (135 mg/kg) compared with 2 and 8 wk postinjury (41 and 44 mg/kg, respectively). In contrast, imipramine lacked significant efficacy at 2 and 8 wk postinjury but slightly attenuated mechanical hypersensitivity at 4 wk postinjury. The results show that drug effects may change over time in the neuropathic state, which should be an important consideration in the evaluation of drugs in preclinical animal pain models and has implications for temporal approaches to therapy in the clinic.     

鞘内注射重组大鼠脂质运载蛋白-2对大鼠吗啡镇痛效能的影响

目的观察鞘内注射重组大鼠脂质运载蛋白-2(LCN2)对大鼠吗啡镇痛效能的影响,并探讨其分子机制。方法健康雄性SD大鼠32只,体重150~180g,采用随机数字表法将鞘内置管成功的大鼠随机分为四组(n=8):Ⅰ组为对照组:鞘内注射MES缓冲液10μl,Ⅱ组、Ⅲ组和Ⅳ组分别鞘内注射10μl含LCN2蛋白0.02、0.2、2μg的MES溶液,每天1次,连续5d。分别在鞘内给药前和给药后第6、7、8天皮下注射吗啡10mg/kg,吗啡注射前和注射后45min测定大鼠热辐射缩足潜伏期(PWTL),并计算最大可能镇痛效应百分比(MPE)。第8天行为学测试结束后处死动物,取脊髓腰膨大,采用Western blot法检测磷酸化p38丝裂原活化蛋白激酶(p-p38 MAPK)的表达;采用免疫组织化学法检测星型胶质细胞标志物胶质纤维酸性蛋白(GFAP)的表达。结果与Ⅰ组和给药前比较,Ⅱ组大鼠鞘内给药后基础PWTL和MPE差异无统计学意义,Ⅲ组、Ⅳ组鞘内给药后第6、7、8天基础PWTL和MPE均明显降低(P0.05);与Ⅰ组比较,Ⅱ组鞘内给药后脊髓腰膨大内pp38 MAPK、脊髓背角GFAP表达差异无统计学意义,Ⅲ组、Ⅳ组脊髓腰膨大内p-p38MAPK、脊髓背角GFAP表达明显增加(P0.05)。结论大鼠连续5d鞘内注射LCN2蛋白0.2、2μg能够诱导热痛敏并导致吗啡镇痛效能下降,其机制可能与活化脊髓内星型胶质细胞和p38 MAPK有关。