Analgesic effect of milnacipran is associated with c-Fos expression in the anterior cingulate cortex in the rat neuropathic pain model.
The objective of the present study was to examine whether milnacipran, a serotonin-noradrenaline reuptake inhibitor, has an analgesic effect in rats with neuropathic pain. In addition, the c-Fos expression was investigated in the supraspinal sites of the brain and in the spinal dorsal horn in association with the nociceptive processing in rats with neuropathic pain produced by chronic constriction injury (CCI) in the sciatic nerve. In the CCI-induced neuropathic rats, behavioral testing for determining the change in the withdrawal threshold to mechanical stimulation and immunohistochemical detection of c-Fos were both performed. The anti-allodynic effect derived from milnacipran gradually increased over the observation period, indicating that the delayed-onset analgesia might be elicited by the continuous administration of milnacipran. The increased level of c-Fos expression in the anterior cingulate cortex (ACC) induced by noxious mechanical stimulation was significantly inhibited by the continuous administration of milnacipran, indicating that milnacipran might cause a functional modification in the nociceptive processing in the ACC.
Takeda
Ryuichiro
R
Department of Psychiatry, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki-gun, Miyazaki 889-1692, Japan. psytr@fc.miyazaki-u.ac.jp
Watanabe
Yuko
Y
Ikeda
Tetsuya
T
Abe
Hiroshi
H
Ebihara
Kosuke
K
Matsuo
Hisae
H
Nonaka
Hiroi
H
Hashiguchi
Hiroyuki
H
Nishimori
Toshikazu
T
Ishida
Yasushi
Y
D000344:Afferent Pathways / Q000187:drug effects / Q000378:metabolism; D000700:Analgesics / Q000627:therapeutic use*; D000818:Animals; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D002908:Chronic Disease / Q000188:drug therapy; D003521:Cyclopropanes / Q000627:therapeutic use*; D004195:Disease Models, Animal; D006179:Gyrus Cinguli / Q000187:drug effects* / Q000378:metabolism*; D007150:Immunohistochemistry; D008026:Ligation; D000078764:Milnacipran; D009437:Neuralgia / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D009619:Nociceptors / Q000187:drug effects / Q000378:metabolism; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D010148:Intractable Pain / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D010523:Peripheral Nervous System Diseases / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology; D020671:Posterior Horn Cells / Q000187:drug effects / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020426:Sciatic Neuropathy / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D000700:Analgesics; D015415:Biomarkers; D003521:Cyclopropanes; D000078764:Milnacipran; D016760:Proto-Oncogene Proteins c-fos; D017367:Selective Serotonin Reuptake Inhibitors