Intracellular Signaling in Primary Sensory Neurons and Persistent Pain

Cheng, Jen-Kun; Ji, Ru-Rong

doi:10.1007/s11064-008-9711-z

Cited by 266Pain Mechanisms and TreatmentsIon Channels and ReceptorsPain Management and Treatment

Intracellular Signaling in Primary Sensory Neurons and Persistent Pain

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Cheng, Jen-Kun, Ji, Ru-Rong·2008·Neurochemical Research

DOI 10.1007/s11064-008-9711-zPMC PMC2570619

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Abstract

During evolution, living organisms develop a specialized apparatus called nociceptors to sense their environment and avoid hazardous situations. Intense stimulation of high threshold C- and Adelta-fibers of nociceptive primary sensory neurons will elicit pain, which is acute and protective under normal conditions. A further evolution of the early pain system results in the development of nociceptor sensitization under injury or disease conditions, leading to enhanced pain states. This sensitization in the peripheral nervous system is also called peripheral sensitization, as compared to its counterpart, central sensitization. Inflammatory mediators such as proinflammatory cytokines (TNF-alpha, IL-1beta), PGE(2), bradykinin, and NGF increase the sensitivity and excitability of nociceptors by enhancing the activity of pronociceptive receptors and ion channels (e.g., TRPV1 and Na(v)1.8). We will review the evidence demonstrating that activation of multiple intracellular signal pathways such as MAPK pathways in primary sensory neurons results in the induction and maintenance of peripheral sensitization and produces persistent pain. Targeting the critical signaling pathways in the periphery will tackle pain at the source.

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Nerve growth factor can act on nerves to cause pain and promote nerve growth.
“NGF can also act on those nerves to produce pain and facilitate nerve growth”
From Chronic pelvic pain and endometriosis: translational evidence of the relationship and implications (2011) · cites this paper as Cheng and Ji, 2008
The Introduction (page not provided) says NGF acts on sensory neurons, sensitizes nociceptors, and contributes to heat hyperalgesia, supporting the pain portion. It discusses NGF's role in maintaining nociceptor phenotype but does not say that NGF facilitates nerve growth. (LLM, conf=0.86)
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Authors: Cheng, J.-K., & Ji, R.-R.
Affiliations: Brigham and Women's Hospital (US)
Corresponding author: Ji, Ru-Rong
ORCID: Cheng, Jen-Kun
Ji, Ru-Rong
Venue: Neurochemical Research
Publisher: Springer Science and Business Media LLC
Published: 2008-04-22
Volume: 33
Issue: 10
Pages: 1970-1978
ISSN: 0364-3190 (ISSN-L)
1573-6903
DOI: 10.1007/s11064-008-9711-z
PMC: PMC2570619
OpenAlex: W1971066754
Cited by: 266
References: 111
Citations by year: 2026: 5 · 2025: 6 · 2024: 6 · 2023: 55 · 2022: 7 · 2021: 9 · 2020: 24 · 2019: 8 · 2018: 12 · 2017: 16 · 2016: 16 · 2015: 12 · 2014: 10 · 2013: 12 · 2012: 12
FWCI: 11.50
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
Locations: Neurochemical Research (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Institutes of Health
National Institute on Aging (P30AG012300)
Fogarty International Center (TW7180, R03TW007180)
National Institute of Neurological Disorders and Stroke (R01NS054932, NS 54932)
National Institute of Dental and Craniofacial Research (R01DE017794, DE17794)
Topics: Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
Health Sciences › Medicine › Anesthesiology and Pain Medicine › Pain Management and Treatment
Keywords: chronic pain, primary sensory neurons, nociceptors, peripheral sensitization, central sensitization, intracellular signaling, MAPK signaling, inflammatory cytokines, TNF-α, IL-1β, prostaglandin E2, bradykinin, nerve growth factor, TRPV1, Nav1.8, inflammatory mediators
MeSH terms: Action Potentials, Animals, Humans, Nociceptors, Pain, Protein Kinase C, Sensory Receptor Cells, Signal Transduction, Cyclic AMP-Dependent Protein Kinases, Peripheral Nervous System, Phosphatidylinositol 3-Kinases, MAP Kinase Signaling System

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Intracellular Signaling in Primary Sensory Neurons and Persistent Pain

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