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Neuromodulation, Specialized Proresolving Mediators, and Resolution of Pain.

Publication ,  Journal Article
Tao, X; Lee, MS; Donnelly, CR; Ji, R-R
Published in: Neurotherapeutics
July 2020

The current crises in opioid abuse and chronic pain call for the development of nonopioid and nonpharmacological therapeutics for pain relief. Neuromodulation-based approaches, such as spinal cord stimulation, dorsal root ganglion simulation, and nerve stimulation including vagus nerve stimulation, have shown efficacy in achieving pain control in preclinical and clinical studies. However, the mechanisms by which neuromodulation alleviates pain are not fully understood. Accumulating evidence suggests that neuromodulation regulates inflammation and neuroinflammation-a localized inflammation in peripheral nerves, dorsal root ganglia/trigeminal ganglia, and spinal cord/brain-through neuro-immune interactions. Specialized proresolving mediators (SPMs) such as resolvins, protectins, maresins, and lipoxins are lipid molecules produced during the resolution phase of inflammation and exhibit multiple beneficial effects in resolving inflammation in various animal models. Recent studies suggest that SPMs inhibit inflammatory pain, postoperative pain, neuropathic pain, and cancer pain in rodent models via immune, glial, and neuronal modulations. It is noteworthy that sham surgery is sufficient to elevate resolvin levels and may serve as a model of resolution. Interestingly, it has been shown that the vagus nerve produces SPMs and vagus nerve stimulation (VNS) induces SPM production in vitro. In this review, we discuss how neuromodulation such as VNS controls pain via immunomodulation and neuro-immune interactions and highlight possible involvement of SPMs. In particular, we demonstrate that VNS via auricular electroacupuncture effectively attenuates chemotherapy-induced neuropathic pain. Furthermore, auricular stimulation is able to increase resolvin levels in mice. Thus, we propose that neuromodulation may control pain and inflammation/neuroinflammatioin via SPMs. Finally, we discuss key questions that remain unanswered in our understanding of how neuromodulation-based therapies provide short-term and long-term pain relief.

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Published In

Neurotherapeutics

DOI

EISSN

1878-7479

Publication Date

July 2020

Volume

17

Issue

3

Start / End Page

886 / 899

Location

United States

Related Subject Headings

  • Vagus Nerve Stimulation
  • Pain Management
  • Pain
  • Neurology & Neurosurgery
  • Neuroimmunomodulation
  • Lipoxins
  • Lipid Metabolism
  • Inflammation Mediators
  • Humans
  • Docosahexaenoic Acids
 

Citation

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Tao, X., Lee, M. S., Donnelly, C. R., & Ji, R.-R. (2020). Neuromodulation, Specialized Proresolving Mediators, and Resolution of Pain. Neurotherapeutics, 17(3), 886–899. https://doi.org/10.1007/s13311-020-00892-9
Tao, Xueshu, Michael S. Lee, Christopher R. Donnelly, and Ru-Rong Ji. “Neuromodulation, Specialized Proresolving Mediators, and Resolution of Pain.Neurotherapeutics 17, no. 3 (July 2020): 886–99. https://doi.org/10.1007/s13311-020-00892-9.
Tao X, Lee MS, Donnelly CR, Ji R-R. Neuromodulation, Specialized Proresolving Mediators, and Resolution of Pain. Neurotherapeutics. 2020 Jul;17(3):886–99.
Tao, Xueshu, et al. “Neuromodulation, Specialized Proresolving Mediators, and Resolution of Pain.Neurotherapeutics, vol. 17, no. 3, July 2020, pp. 886–99. Pubmed, doi:10.1007/s13311-020-00892-9.
Tao X, Lee MS, Donnelly CR, Ji R-R. Neuromodulation, Specialized Proresolving Mediators, and Resolution of Pain. Neurotherapeutics. 2020 Jul;17(3):886–899.
Journal cover image

Published In

Neurotherapeutics

DOI

EISSN

1878-7479

Publication Date

July 2020

Volume

17

Issue

3

Start / End Page

886 / 899

Location

United States

Related Subject Headings

  • Vagus Nerve Stimulation
  • Pain Management
  • Pain
  • Neurology & Neurosurgery
  • Neuroimmunomodulation
  • Lipoxins
  • Lipid Metabolism
  • Inflammation Mediators
  • Humans
  • Docosahexaenoic Acids