Background & Aims

Sympathectomy or localized sympathetic blocks are used to treat visceral, vascular, and neuropathic pain in humans. In animal models, sympathetic innervations of the sensory ganglia are believed to play pivotal role in various pathological pain conditions by regulating local immune/inflammatory responses, never regeneration, and abnormal neuronal firing. Recently, our lab found that a localized “microsympathectomy” (mSYMPX), i.e. cutting the lumbar sympathetic postganglionic grey rami, resulted in death of sensory neurons in the DRG in rats and mice. Here, we investigated possible functional consequences of sympathectomy-induced cell death and its underlying mechanisms.

Methods

Adult mice of both sexes received mSYMPX or sham on the right side near L4 and L3 DRGs followed by behavioral measures of mechanical and thermal sensitivity of the hind paws and in vivo calcium imaging.

Results

We found the mSYMPX significantly decreased responses to pinprick applied to the ventral surface of the ipsilateral hindpaws. We next measured the number of L4 DRG neurons activated by mechanical stimulation of the hindpaws via in vivo calcium imaging in GCaMP6s/Pirt-cre mice. We found that the number of neurons responding to paw poking with a series of von-Frey filaments was significantly reduced in the right, sympathectomized L4 DRG compared to the contralateral side. The reduction was observed for both innoxious and noxious mechanical stimuli. Similar results were observed at all examined time points (days 1, 3, 7 and 28). We further examined neuronal cell death after mSYMPX and found reduced fluorescently labeled sensory neuron projections to the ipsilateral spinal cord, downregulated anti-apoptotic proteins, and upregulated apoptotic proteins after mSYMPX.

Conclusions

Our results suggest that DRG sensory neuron death may contribute to sympathectomy-induced hypoalgesia and that sensory neuron survival in adult mice depends on intact sympathetic innervations.

References

Xie W, Strong JA, Zhang J-M. Localized sympathectomy reduces peripheral nerve regeneration and pain behaviors in two rat neuropathic pain models. Pain. 2020, 161:1925-1936.
Zhu, X., Xie, W., Zhang, J.-D., Strong, J. A., and Zhang, J.-M: Sympathectomy decreases pain behaviors and nerve regeneration by downregulating monocyte chemokine CCL2 in dorsal root ganglia in the rat tibial nerve crush model. Pain. 2022, 163:e106-e120.
Tonello R, Xie W, Lee SH, Wang M, Liu X, Strong JA, Zhang J-M, Berta T. Local Sympathectomy Promotes Anti-inflammatory Responses and Relief of Paclitaxel-induced Mechanical and Cold Allodynia in Mice. Anesthesiology. 2020, 132:1540-1553
Xie, W., Chen, S., Strong, J.A., Li, A-L, Lewkowich, I.P., and Zhang, J-M. Localized sympathectomy reduces mechanical hypersensitivity by restoring normal immune homeostasis in rat models of inflammatory pain. J Neurosci, 2016, 36(33): 8712-8725.

Presenting Author

Debora Denardin Lückemeyer

Poster Authors

Debora Denardin Lückemeyer

PhD

University of Cincinnati

Lead Author

E-mail

Wenrui Xie; PhD

University of Cincinnati

Lead Author

E-mail

Beatriz Lima Adjafre

MSc

University of Cincinnati

Lead Author

E-mail

Judith A. Strong

PhD

University of Cincinnati

Lead Author

E-mail

Temugin Berta

University of Cincinnati

Lead Author

E-mail

Jun-Ming Zhang

University of Cincinnati

Lead Author

E-mail

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