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Cited by 1,314Pain Mechanisms and TreatmentsIon Channels and ReceptorsNeuroinflammation and Neurodegeneration Mechanisms

Pain regulation by non-neuronal cells and inflammation

Open access
Ji, Ru-Rong, Chamessian, Alexander, Zhang, Yu-Qiu·2016·Science
DOI 10.1126/science.aaf8924PMC PMC5488328
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Abstract

Acute pain is protective and a cardinal feature of inflammation. Chronic pain after arthritis, nerve injury, cancer, and chemotherapy is associated with chronic neuroinflammation, a local inflammation in the peripheral or central nervous system. Accumulating evidence suggests that non-neuronal cells such as immune cells, glial cells, keratinocytes, cancer cells, and stem cells play active roles in the pathogenesis and resolution of pain. We review how non-neuronal cells interact with nociceptive neurons by secreting neuroactive signaling molecules that modulate pain. Recent studies also suggest that bacterial infections regulate pain through direct actions on sensory neurons, and specific receptors are present in nociceptors to detect danger signals from infections. We also discuss new therapeutic strategies to control neuroinflammation for the prevention and treatment of chronic pain.

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  • Non-neuronal cells, including circulating and central immune cells, have been implicated in the modulation of chronic pain through the regulation of central sensitization.

    “Non-neuronal cells, including circulating and central immune cells, have been implicated in the modulation of chronic pain through the regulation of central sensitization (11).”

    From Nociplastic pain: the prominent role of non-neuronal cells in central and peripheral sensitization (2026) · cites this paper as [11]

    The Introduction links central sensitization to chronic pain, and the section on central glial cells describes microglial mediators changing spinal synaptic transmission and enhancing pain signaling. The T-Lymphocytes section also reports that infiltrating T cells affect pain sensitivity. However, the Monocytes and macrophages section describes circulating cells acting mainly in the periphery and says their spinal infiltration after nerve injury is limited; the review does not establish central sensitization as the mechanism for circulating immune cells generally. Page numbers are unavailable in our copy. (LLM, conf=0.84)

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Cited by

Sorted by citations

Authors
Ji, R.-R., Chamessian, A., & Zhang, Y.-Q.
Affiliations
  • Duke Medical Center (US)
  • Fudan University (CN)
Corresponding author
Ji, Ru-Rong
ORCID
Venue
Science
Publisher
American Association for the Advancement of Science (AAAS)
Published
2016-11-04
Volume
354
Issue
6312
Pages
572-577
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
DOI
10.1126/science.aaf8924
PMC
PMC5488328
OpenAlex
W2547814918
Cited by
1,314
References
6
Citations by year
2026: 125 · 2025: 150 · 2024: 149 · 2023: 150 · 2022: 172 · 2021: 170 · 2020: 147 · 2019: 102 · 2018: 92 · 2017: 55 · 2014: 1
FWCI
9.74
Type
journal article
Language
en
Open access
Locations
  • Science (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • DukeSpace (Duke University) (submittedVersion, cc-by-nc-nd)
Funders
  • NIH (DE17794, DE22743, NS87988)
  • National Natural Science Foundation of China (31420103903)
Topics
  • Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
  • Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
pain modulation, non-neuronal cells, neuroinflammation, chronic pain, acute pain, nociceptors, glial cells, immune cells, keratinocytes, cancer pain, chemotherapy-induced pain, nerve injury, bacterial infection, damage-associated molecular patterns, pain resolution, pain therapeutics
MeSH terms
Animals, Bacterial Infections, Ganglia, Spinal, Humans, Macrophages, Monocytes, Neoplasms, Neuritis, Neuroglia, Nociceptors, Pain, Spinal Cord, T-Lymphocytes, Keratinocytes, Toll-Like Receptors, Mice, Rats, Chronic Pain

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