Perrot S, Guilbaud G, Kayser V
Unité de Recherches de Physiopharmacologie du Système Nerveux, INSERM U161, 2 rue d'Alésia, 75014, Paris, France.
Pain. 1999 Nov;83(2):249-57. doi: 10.1016/s0304-3959(99)00110-4.
Recent studies suggest that peripheral morphine may represent a valuable treatment in inflammatory painful diseases. This study examined effects of intraplantar morphine against noxious pressure and paw edema in rats with repeated acute inflammation induced by two carrageenin injections 7 days apart. This model mimics at least partly some aspects of recurrent inflammatory pain encountered in the clinical situation. In the first part of the experiment, the effect of intraplantar morphine into the inflamed hindpaw was determined 3 h after carrageenin injection. Intraplantar morphine (50-200 microg) produced significant elevations of vocalization thresholds to paw pressure in inflamed but not in non-inflamed paws after both carrageenin injection; these effects were reversible by intraplantar naloxone methiodide (40 microg). The effects of intraplantar morphine (150 microg) were similar in magnitude to that of intravenous morphine (1 mg/kg) after first carrageenin injection. In contrast, at doses of 150-200 microg, they were significantly lower after second ipsilateral carrageenin injection 7 days later, than first injection. Intraplantar morphine (100-200 microg) had no effect on paw edema associated with both carrageenin injections. In the second part of the experiment, intraplantar morphine was injected 10 min before the first injection of carrageenin. Intraplantar morphine (50 microg) was ineffective, whereas morphine (100-200 microg) prevented reduction of vocalization thresholds to paw pressure of inflamed hindpaw for 3 h. The intraplantar injection of morphine (100 and 150 microg) produced a transient increase in the volume of inflamed hindpaw, not reversible by intraplantar naloxone methiodide (40 microg). Pretreatment with intraplantar morphine had no effect on reduction of vocalization thresholds to paw pressure and edema related to a second ipsilateral injection of carrageenin 7 days later. These findings suggest that peripheral morphine may be useful for the clinical management of acute inflammatory pain rather than in recurrent inflammatory painful situations.
最近的研究表明，外周给予吗啡可能是治疗炎性疼痛性疾病的一种有效方法。本研究考察了足底注射吗啡对间隔7天两次注射角叉菜胶诱导的反复急性炎症大鼠的伤害性压力和爪部水肿的影响。该模型至少部分模拟了临床中遇到的复发性炎性疼痛的某些方面。在实验的第一部分，在注射角叉菜胶3小时后测定向发炎后爪足底注射吗啡的效果。在两次注射角叉菜胶后，足底注射吗啡（50 - 200微克）使发炎爪部对爪部压力的发声阈值显著升高，但对未发炎爪部无此作用；这些作用可被足底注射甲基硫酸纳洛酮（40微克）逆转。首次注射角叉菜胶后，足底注射吗啡（150微克）的效果在程度上与静脉注射吗啡（1毫克/千克）相似。相反，在7天后第二次同侧注射角叉菜胶后，剂量为150 - 200微克时，其效果显著低于首次注射。足底注射吗啡（100 - 200微克）对两次注射角叉菜胶所致的爪部水肿均无作用。在实验的第二部分，在首次注射角叉菜胶前10分钟注射足底吗啡。足底注射吗啡（50微克）无效，而吗啡（100 - 200微克）可使发炎后爪对爪部压力的发声阈值在3小时内不降低。足底注射吗啡（100和150微克）使发炎后爪体积短暂增加，且不能被足底注射甲基硫酸纳洛酮（40微克）逆转。预先足底注射吗啡对7天后第二次同侧注射角叉菜胶所致的爪部压力发声阈值降低和水肿无作用。这些发现表明，外周给予吗啡可能对急性炎性疼痛的临床治疗有用，而非用于复发性炎性疼痛情况。
