首页|The Antinociceptive Effect of Sympathetic Block is Mediated by Transforming Growth Factor β in a Mouse Model of Radiculopathy
The Antinociceptive Effect of Sympathetic Block is Mediated by Transforming Growth Factor β in a Mouse Model of Radiculopathy
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Although sympathetic blockade is clinically used to treat pain,the underlying mechanisms remain unclear.We developed a localized microsympathectomy(mSYMPX),by cutting the grey rami entering the spinal nerves near the rodent lumbar dorsal root ganglia(DRG).In a chem-otherapy-induced peripheral neuropathy model,mSYMPX attenuated pain behaviors via DRG macrophages and the anti-inflammatory actions of transforming growth factor-β(TGF-β)and its receptor TGF-βR1.Here,we examined the role of TGF-β in sympathetic-mediated radiculopathy produced by local inflammation of the DRG(LID).Mice showed mechanical hypersensitivity and transcriptional and protein upregulation of TGF-β1 and TGF-βR1 three days after LID.Microsympathectomy prevented mechanical hypersensitivity and further upregulated Tgfb1 and Tgfbr1.Intrathecal delivery of TGF-β1 rapidly relieved the LID-induced mechanical hypersensitivity,and TGF-βR1 antago-nists rapidly unmasked the mechanical hypersensitivity after LID+mSYMPX.In situ hybridization showed that Tgfb1 was largely expressed in DRG macrophages,and Tgfbr1 in neurons.We suggest that TGF-β signaling is a general underlying mechanism of local sympathetic blockade.
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维普
