The monoamine reuptake inhibitor milnacipran does not affect nociception to acute visceral distension in rats.
The role of antidepressants in the treatment of visceral pain has not been extensively examined. Milnacipran, an antidepressant that inhibits monoamine reuptake, is widely used in the treatment of depression and fibromyalgia. In this study, we sought to determine the activity of milnacipran against acute visceral nociception. Female virgin rats were studied 7 days after bilateral ovariectomy. For uterine cervical distension (UCD), two metal rods were inserted into the cervical osses under general anesthesia for manual distension. Colorectal distension (CRD) was performed by insertion of a balloon catheter into the descending colon and rectum, followed by manual inflation. Two electrodes were inserted into the rectus abdominus muscle for recording UCD- or CRD-induced reflex contraction, which was quantified by electromyography (EMG). A dose response for milnacipran, administered intrathecally or i.v., was obtained for UCD and CRD stimulation. Milnacipran failed to inhibit the UCD-induced EMG response, whether administered i.v. or intrathecally. Similarly, i.v. milnacipran, administered either acutely or chronically, failed to inhibit the CRD-induced EMG response. CRD and UCD are well established animal models for the study of acute visceral pain. Milnacipran, although it provides some unique advantages compared with other antidepressants, is unlikely to produce analgesia after acute administration in the setting of acute visceral pain.


CONCLUSIONS
Neither intrathecal nor i.v. milnacipran, a monoamine reuptake inhibitor, inhibits an acute visceral pain response induced by colorectal or uterine cervical distension.
Shin
Sang-Wook
SW
Department of Anesthesiology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA.
Eisenach
James C
JC
Rao
Srinias G
SG
Tong
Chuanyao
C
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D002404:Catheterization; D003000:Clonidine / Q000494:pharmacology; D003106:Colon / Q000502:physiology; D003521:Cyclopropanes / Q000494:pharmacology*; D004576:Electromyography / Q000187:drug effects; D005260:Female; D007275:Injections, Intravenous; D007278:Injections, Spinal; D000078764:Milnacipran; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology*; D010052:Ovariectomy; D010146:Pain / Q000503:physiopathology*; D010812:Physical Stimulation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012007:Rectum / Q000502:physiology; D014599:Uterus / Q000502:physiology
D000316:Adrenergic alpha-Agonists; D003521:Cyclopropanes; D014179:Neurotransmitter Uptake Inhibitors; D000078764:Milnacipran; D003000:Clonidine