BACKGROUND: Serotonin and norepinephrine are known as agents of the nonopiate endogenous descending pain control system. Recently, selective serotonin norepinephrine receptor inhibitors (SNRIs) have been developed as antidepressants. We studied the effects of milnacipran, a SNRI in a spinal nerve ligation (SNL) model and formalin test.

METHODS: Male Sprague-Dawley rats weighing 200-250 gm were used for this study. In the SNL model, under an anesthetic state, the 5th lumbar spinal nerve was ligated and a PE-10 catheter was inserted into the subarachnoid space. Milnacipran was injected intraperitoneally or intrathecally and the threshold of tactile allodynia was measured. In the formalin test, milnacipran was administered intraperitoneally or intrathecally. 30 minutes after intraperitoneal injection or 60 minutes after intrathecal injection the formalin test was performed and flinching was counted for 60 minutes.

RESULTS: In the spinal nerve ligation model, pain response decreased significantly (P < 0.05). But, after intraperitoneal milnacipran administration in the spinal nerve ligation model, no difference in mechanical allodynia was observed between among groups. In formalin test, intraperitoneal and intrathecal milnacipran administration decreased phase I response, but there was no change in phase II response.

CONCLUSIONS: Milnacipran reduced neuropathic pain after intrathecal administration. But there was no difference after intraperitoneal administration. Intraperitoneal and intrathecal milnacipran administration in formalin test reduced only the acute phase, but no difference in chronic chemical induced centralization pain was observed.