The Antinociceptive Effect of Sympathetic Block is Mediated by Transforming Growth Factor β in a Mouse Model of Radiculopathy

AbstractAlthough 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 chemotherapy-induced peripheral neuropathy model, mSYMPX attenuated pain behaviorsvia 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. Micros ympathectomy prevented mechanical hypersensitivity and further upregulatedTgfb1 andTgfbr1. Intrathecal delivery of TGF- β1 rapidly relieved the LID-induced mechanical hypersensitivity, and TGF-βR1 antagonists rapidly unmasked the mechanical hypersensitivity after LID+mSYMPX.In situ hybridization showed thatTgfb1 was largely expressed in DRG macrophages, andTgfbr1 in neurons. We suggest that TGF- β signaling is a general underlying mechanism of local sympathetic blockade.
Source: Neuroscience Bulletin - Category: Neuroscience Source Type: research