Spinal Cord Stimulation Enhances Microglial Activation in the Spinal Cord of Nerve-Injured Rats

Abstract

Microglia can modulate spinal nociceptive transmission. Yet, their role in spinal cord stimulation (SCS)-induced pain inhibition is unclear. Here, we examined how SCS affects microglial activation in the lumbar cord of rats with chronic constriction injury (CCI) of the sciatic nerve. Male rats received conventional SCS (50 Hz, 80% motor threshold, 180 min, 2 sessions/day) or sham stimulation on days 18–20 post-CCI. SCS transiently attenuated the mechanical hypersensitivity in the ipsilateral hind paw and increased OX-42 immunoreactivity in the bilateral dorsal horns. SCS also upregulated the mRNAs of M1-like markers, but not M2-like markers. Inducible NOS protein expression was increased, but brain-derived neurotrophic factor was decreased after SCS. Intrathecal minocycline (1 μg–100 μg), which inhibits microglial activation, dose-dependently attenuated the mechanical hypersensitivity. Pretreatment with low-dose minocycline (1 μg, 30 min) prolonged the SCS-induced pain inhibition. These findings suggest that conventional SCS may paradoxically increase spinal M1-like microglial activity and thereby compromise its own ability to inhibit pain.

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Acknowledgements

We thank Claire F. Levine, MS, ELS (Scientific Editor, Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University), for editing the manuscript and Medtronic, Inc. (Minneapolis, MN, USA) for generously providing the rodent electrodes for spinal cord stimulation. This work was supported by a grant from the Neurosurgery Pain Research Institute at the Johns Hopkins University and subsidized by the National Institutes of Health (Bethesda, Maryland, USA) (NS110598). The efforts of B.S. were supported by an award from the China Scholarship Council for Chinese PhD candidates to study abroad.

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Correspondence to Yun Guan.

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Dr. Yun Guan received research grant support from Medtronic, Inc., Minneapolis, MN. However, none of the authors has a commercial interest in the material presented in this paper. There are no other relationships that might lead to a conflict of interest in the current study. The authors declare no competing interests.

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Shu, B., He, S. & Guan, Y. Spinal Cord Stimulation Enhances Microglial Activation in the Spinal Cord of Nerve-Injured Rats. Neurosci. Bull. (2020). https://doi.org/10.1007/s12264-020-00568-6

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Keywords

  • Spinal cord stimulation
  • Microglia
  • Neuropathic pain
  • Spinal cord
  • Rat