Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, USA.
Eur J Pain. 2012 Aug;16(7):1021-32. doi: 10.1002/j.1532-2149.2012.00148.x. Epub 2012 Apr 16.
The analgesic properties and mechanisms of loperamide hydrochloride, a peripherally acting opioid receptor agonist, in neuropathic pain warrant further investigation.
We examined the effects of systemic or local administration of loperamide on heat and mechanical hyperalgesia in rats after an L5 spinal nerve ligation (SNL).
(1) Systemic loperamide (0.3-10 mg/kg, subcutaneous in the back) dose dependently reversed heat hyperalgesia in SNL rats, but did not produce thermal analgesia. Systemic loperamide (3 mg/kg) did not induce thermal antinociception in naïve rats; (2) systemic loperamide-induced anti-heat hyperalgesia was blocked by pretreatment with intraperitoneal naloxone methiodide (5 mg/kg), but not by intraperitoneal naltrindole (5 mg/kg) or intrathecal naltrexone (20 μg/10 μL); (3) local administration of loperamide (150 μg), but not vehicle, into plantar or dorsal hind paw tissue induced thermal analgesia in SNL rats and thermal antinociception in naïve rats; (4) the analgesic effect of intraplantar loperamide (150 μg/15 μL) in SNL rats at 45 min, but not 10 min, post-injection was blocked by pretreatment with an intraplantar injection of naltrexone (75 μg/10 μL); (5) systemic (3.0 mg/kg) and local (150 μg) loperamide reduced the exaggerated duration of hind paw elevation to noxious pinprick stimuli in SNL rats. Intraplantar injection of loperamide also decreased the frequency of pinprick-evoked response in naïve rats.
These findings suggest that both systemic and local administration of loperamide induce an opioid receptor-dependent inhibition of heat and mechanical hyperalgesia in nerve-injured rats, but that local paw administration of loperamide also induces thermal and mechanical antinociception.
盐酸洛哌丁胺作为一种外周作用阿片受体激动剂，其在神经性疼痛中的镇痛特性和机制值得进一步研究。
我们检测了全身或局部给予洛哌丁胺对 L5 脊神经结扎（SNL）后大鼠热和机械性痛觉过敏的影响。
（1）全身给予洛哌丁胺（背部皮下 0.3-10mg/kg）剂量依赖性地逆转 SNL 大鼠的热痛觉过敏，但不产生热镇痛作用。全身给予洛哌丁胺（3mg/kg）在未受伤的大鼠中不会引起热镇痛作用；（2）洛哌丁胺诱导的抗热痛觉过敏作用被腹腔内纳洛酮甲碘化物（5mg/kg）预处理阻断，但被腹腔内纳曲吲哚（5mg/kg）或鞘内纳曲酮（20μg/10μL）预处理不阻断；（3）局部给予洛哌丁胺（150μg），而不是载体，进入足底或背侧后爪组织，在 SNL 大鼠中引起热镇痛作用，并在未受伤的大鼠中引起热镇痛作用；（4）SNL 大鼠足底注射洛哌丁胺（150μg/15μL）45 分钟后的镇痛作用，但不是 10 分钟后的镇痛作用，被足底注射纳曲酮（75μg/10μL）预处理阻断；（5）全身（3.0mg/kg）和局部（150μg）洛哌丁胺减少了 SNL 大鼠对有害针刺刺激的后爪抬高时间的延长。足底注射洛哌丁胺也减少了未受伤大鼠对针刺诱发反应的频率。
这些发现表明，全身和局部给予洛哌丁胺均可抑制神经损伤大鼠的热痛觉过敏和机械性痛觉过敏，但局部足部给予洛哌丁胺也可诱导热和机械性镇痛。
