TY - JOUR
T1 - Analgesic effect of milnacipran is associated with c-Fos expression in the anterior cingulate cortex in the rat neuropathic pain model
AU - Takeda, Ryuichiro
AU - Watanabe, Yuko
AU - Ikeda, Tetsuya
AU - Abe, Hiroshi
AU - Ebihara, Kosuke
AU - Matsuo, Hisae
AU - Nonaka, Hiroi
AU - Hashiguchi, Hiroyuki
AU - Nishimori, Toshikazu
AU - Ishida, Yasushi
N1 - Funding Information:
The authors wish to thank Asahi Kasei Pharma, Tokyo, Japan, for their generous gift of milnacipran. This research was supported by Grants-in-Aid for Scientific Research from the Japanese Society for the Promotion for Science. We thank Ms. Fumiko Tsuda for excellent technical assistance.
PY - 2009/8
Y1 - 2009/8
N2 - 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.
AB - 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.
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U2 - 10.1016/j.neures.2009.04.010
DO - 10.1016/j.neures.2009.04.010
M3 - Article
C2 - 19383518
AN - SCOPUS:67349150717
VL - 64
SP - 380
EP - 384
JO - Neuroscience Research
JF - Neuroscience Research
SN - 0168-0102
IS - 4
ER -