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Administrations of thalidomide into the rostral ventromedial medulla produce antinociceptive effects in a rat model of postoperative pain
Authors:Tieying Song  Xiaojing Ma  Pengyu Ma  Kunfeng Gu  Jianhui Zhao  Yunliang Yang  Bo Jiang  Yuxia Li  Chunping Wang
Affiliation:Department of Anesthesiology, The First Hospital of Shijiazhuang, No. 36 Fanxi Road, Chang'an District, Shijiazhuang, Hebei province, China
Abstract:The rostral ventromedial medulla (RVM) is highly involved in pain signal transmissions. Previous studies have shown that thalidomide is anti‐nociceptive. Thus, we evaluated the neurobiological mechanisms of thalidomide in the RVM in the regulation of postoperative pain. We used a rat model of postoperative pain to investigate the effects of intra‐RVM thalidomide treatments on postoperative pain, and evaluate the role of cannabinoid receptors in the effects of intra‐RVM thalidomide treatments on GABAergic neurotransmission in the RVM neurons. We found intra‐RVM thalidomide treatments reduced incisional surgery induced mechanical allodynia. This phenomenon was associated with attenuation of the frequency and amplitude of miniature inhibitory postsynaptic currents (mIPSCs) and spontaneous IPSCs (sIPSCs) in RVM neurons. Furthermore, applications of WIN 55,212‐3 mesylate, a non‐selective cannabinoid receptor antagonist reversed the effects of repeated thalidomide treatment on the frequency but not the amplitude of mIPSCs and sIPSCs. Finally, we found that repeated thalidomide treatment robustly enhanced CB2 receptor expression, but slightly reduced CB1 receptor expression, in the RVM. These results suggested that the antinociceptive effects of thalidomide in the RVM likely involve the attenuation of GABA release, which are critically regulated by cannabinoid receptors.
Keywords:thalidomide  postoperative pain  rostral ventromedial medulla  cannabinoid receptor  antinociceptive effects
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