Jagla Grzegorz, Mika Joanna, Makuch Wioletta, Obara Ilona, Wordliczek Jerzy, Przewlocka Barbara
Department of Pain Treatment and Palliative Care, University Hospital, Kraków, Poland; Department of Anatomy, Medical College Jagiellonian University, Kraków, Poland.
Department of Pain Pharmacology, Institute of Pharmacology, Kraków, Poland.
Pharmacol Rep. 2014 Jun;66(3):459-65. doi: 10.1016/j.pharep.2013.11.004. Epub 2014 Apr 3.
The therapy of neuropathic pain may include the use of co-analgesics, such as antidepressants, however, their desired analgesic effect is associated with significant side effects. An alternative approach to this is their local administration which has been proposed, but there is little data regarding their local co-administration with morphine and the nature of the interaction between morphine and either doxepin or venlafaxine, two antidepressant drugs that have been recently used in neuropathic pain therapies.
This study was performed on rats after chronic constriction injury (CCI) to the sciatic nerve. The von Frey and Hargreaves' tests were used to assess mechanical allodynia and thermal hyperalgesia, respectively, after intraplantar (ipl) or subcutaneous (sc) administration of amitriptyline, doxepin, or venlafaxine, or their ipl co-administration with morphine on day 12-16 after injury.
The ipl administration of amitriptyline (3, 15 mg), doxepin (1, 5, 10, 15 mg), or venlafaxine (2, 7 mg) was effective in antagonizing CCI-induced allodynia. Their sc injection at a site distal to the injured side, did not induce alterations in pain thresholds, which supports the local mode of action. Of the three antidepressants used in this study, only ipl co-administration of amitriptyline with morphine significantly enhanced its effect in contrast to doxepin and venlafaxine, both of which weakened the analgesic effect of morphine.
In summary, the results suggest that when amitriptyline (but not doxepin or venlafaxine) is locally co-administered with morphine the effectiveness under neuropathic pain is enhanced, although additional studies are necessary to explain differential mechanisms of interaction of antidepressant drugs with morphine after local administration.
神经性疼痛的治疗可能包括使用辅助镇痛药，如抗抑郁药，然而，它们预期的镇痛效果伴随着显著的副作用。对此的一种替代方法是局部给药，这一方法已被提出，但关于它们与吗啡局部联合给药以及吗啡与多塞平或文拉法辛（最近用于神经性疼痛治疗的两种抗抑郁药）之间相互作用的性质的数据很少。
本研究在大鼠坐骨神经慢性缩窄损伤（CCI）后进行。在损伤后第12 - 16天，通过足底内（ipl）或皮下（sc）给予阿米替林、多塞平或文拉法辛，或它们与吗啡的ipl联合给药后，分别使用von Frey和哈格里夫斯试验来评估机械性异常性疼痛和热痛觉过敏。
足底内给予阿米替林（3、15毫克）、多塞平（1、5、10、15毫克）或文拉法辛（2、7毫克）可有效对抗CCI诱导的异常性疼痛。在损伤侧远端部位进行皮下注射，未引起疼痛阈值的改变，这支持了局部作用模式。在本研究中使用的三种抗抑郁药中，与多塞平和文拉法辛相比，只有阿米替林与吗啡的ipl联合给药显著增强了其效果，而后两者均减弱了吗啡的镇痛效果。
总之，结果表明，当阿米替林（而非多塞平或文拉法辛）与吗啡局部联合给药时，神经性疼痛情况下的有效性会增强，尽管需要进一步研究来解释局部给药后抗抑郁药与吗啡相互作用的不同机制。
