Yoshimura M, Yonehara N
Central Research Laboratory of Maruishi Pharmaceutical Co., LTD., 2-2-18 Imazunaka, Tsurumi-ku, Osaka 538-0042, Japan.
Pharmacol Res. 2001 Aug;44(2):105-11. doi: 10.1006/phrs.2001.0830.
We investigated the effect of topical application of capsaicin cream on withdrawal latency in the hind foot of rat in response to radiant heat in an experimental model of neuropathic pain. A neuropathic state was induced by loose ligation of the sciatic nerve with chromic gut suture. A marked thermal hyperalgesia was observed in response to heat stimulus applied to the operated side from 3 days through 2 weeks, followed by a gradual return to the control level by 35 days after surgery. Capsaicin cream applied to both the bilateral hind instep and sole once a day for a continuous period of 2 weeks or 4 weeks alleviated thermal hyperalgesia in a dose-dependent manner. A remarkable effect was observed 2 weeks after the start of the application and this effect proved to be reversible. On the other hand, in sham-operated animals when capsaicin cream was applied once daily from day 7 after the sham operation, from 1 day through 3 weeks following capsaicin application, withdrawal latency of the sham-operated paws of the capsaicin-treated group was significantly increased as compared to that of the vehicle cream-treated group. The effects of antagonists of glutamate receptor and tachykinin receptors were investigated 7 days post surgery. Pretreatment with MK-801 (0.5 mg kg(-1), i.p.), but not with CNQX (0.5 mg kg(-1), i.p.), reversed the thermal hyperalgesia following nerve injury. Neither of RP67580 (1--10 mg kg(-1), i.p.) nor SR48968 (1--10 mg kg(-1), i.p.) had any effect on the withdrawal latency in the injured and non-injured hind paw. These results suggest that although the manifestation of effectiveness may be delayed by changes in networks of neurotransmitters related to the nociceptive pathways following nerve injury, longer-term repetitive application of capsaicin cream has a significant therapeutic effect on subjects with painful peripheral neuropathy.
在神经性疼痛实验模型中，我们研究了局部应用辣椒素乳膏对大鼠后足对辐射热的撤足潜伏期的影响。通过用铬制肠线对坐骨神经进行宽松结扎诱导出神经病变状态。从术后3天到2周，对手术侧施加热刺激时观察到明显的热痛觉过敏，术后35天逐渐恢复到对照水平。每天一次在双侧后足背和足底连续涂抹2周或4周的辣椒素乳膏，以剂量依赖的方式减轻热痛觉过敏。在开始涂抹后2周观察到显著效果，且该效果被证明是可逆的。另一方面，在假手术动物中，从假手术后第7天开始每天涂抹一次辣椒素乳膏，在涂抹辣椒素后1天到3周，与赋形剂乳膏处理组相比，辣椒素处理组假手术爪子的撤足潜伏期显著增加。在术后7天研究了谷氨酸受体拮抗剂和速激肽受体拮抗剂的作用。用MK - 801（0.5mg/kg，腹腔注射）预处理可逆转神经损伤后的热痛觉过敏，但用CNQX（0.5mg/kg，腹腔注射）预处理则不能。RP67580（1 - 10mg/kg，腹腔注射）和SR48968（1 - 10mg/kg，腹腔注射）对受伤和未受伤后爪的撤足潜伏期均无任何影响。这些结果表明，尽管神经损伤后与伤害性感受通路相关的神经递质网络变化可能会延迟疗效的显现，但长期重复应用辣椒素乳膏对疼痛性周围神经病变患者具有显著的治疗效果。
