Abstract
Introduction
Despite increasing utilization of spinal cord stimulation (SCS), its effects on chemoefficacy,
cancer progression, and chemotherapy-induced peripheral neuropathy (CIPN) pain remain
unclear. Up to 30% of adults who are cancer survivors may suffer from CIPN, and there
are currently no effective preventative treatments.
Materials and Methods
Through a combination of bioluminescent imaging, behavioral, biochemical, and immunohistochemical
approaches, we investigated the role of SCS and paclitaxel (PTX) on tumor growth and
PTX-induced peripheral neuropathy (PIPN) pain development in T-cell–deficient male rats (Crl:NIH-Foxn1rnu) with xenograft human non–small cell lung cancer. We hypothesized that SCS can prevent
CIPN pain and enhance chemoefficacy partially by modulating macrophages, fractalkine
(CX3CL1), and inflammatory cytokines.
Results
We show that preemptive SCS enhanced the antitumor efficacy of PTX and prevented PIPN
pain. Without SCS, rats with and without tumors developed robust PIPN pain-related
mechanical hypersensitivity, but only those with tumors developed cold hypersensitivity,
suggesting T-cell dependence for different PIPN pain modalities. SCS increased soluble
CX3CL1 and macrophages and decreased neuronal and nonneuronal insoluble CX3CL1 expression
and inflammation in dorsal root ganglia.
Conclusion
Collectively, our findings suggest that preemptive SCS is a promising strategy to
increase chemoefficacy and prevent PIPN pain via CX3CL1-macrophage modulation.
Keywords
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Article info
Publication history
Published online: April 11, 2023
Accepted:
March 13,
2023
Received in revised form:
February 19,
2023
Received:
January 5,
2023
Publication stage
In Press Corrected ProofFootnotes
Source(s) of financial support: This study was conducted at the Johns Hopkins University and supported by grants from the National Cancer Institute–National Institutes of Health (Bethesda, MD) CA255428 (Eellan Sivanesan); the Foundation of Anesthesia Education and Research (Eellan Sivanesan); the American Society of Regional Anesthesia and Pain Medicine (Eellan Sivanesan); the Blaustein Pain Education and Research Endowment (Eellan Sivanesan); and the Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University–School of Medicine, Stimulating and Advancing ACCM Research Award (Eellan Sivanesan). This study was partially supported by grants from the National Institute of Neurological Disorders and Stroke (NINDS)—National Institutes of Health (NIH) (Bethesda, MD) NS110598 and NINDS–NIH NS117761 (Yun Guan). Funders had no role in study design, data collection, or data interpretation, or in the decision to submit the work for publication.
Conflict of Interest: Eellan Sivanesan, Karla R. Sanchez, Chi Zhang, Shao-Qiu He, and Kimberly E. Stephens reported no conflict of interest. Bengt Linderoth is a consultant for Elekta AB. Srinivasa N. Raja is a consultant for AbbVie, Averitas Pharma, Bayer, and Lexicon Pharmaceuticals. Yun Guan and Srinivasa N. Raja are principal and coinvestigators in a research grant from Medtronic, Inc. Yun Guan received a research award from TissueTech, Inc.
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© 2023 International Neuromodulation Society. Published by Elsevier Inc. All rights reserved.
