Cited by 2,685Pain Mechanisms and TreatmentsIon Channels and ReceptorsIon channel regulation and function

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Molecular mechanisms of nociception

Julius, David, Basbaum, Allan I.·2001·Nature

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Abstract

The sensation of pain alerts us to real or impending injury and triggers appropriate protective responses. Unfortunately, pain often outlives its usefulness as a warning system and instead becomes chronic and debilitating. This transition to a chronic phase involves changes within the spinal cord and brain, but there is also remarkable modulation where pain messages are initiated - at the level of the primary sensory neuron. Efforts to determine how these neurons detect pain-producing stimuli of a thermal, mechanical or chemical nature have revealed new signalling mechanisms and brought us closer to understanding the molecular events that facilitate transitions from acute to persistent pain.

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Self-citation
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“Some sensory neurons (Aδ-fiber and C-fiber) have high thresholds of activation and only generate action potentials in response to noxious stimuli [1].”
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“Both of the compounds also showed significant anti-inflammatory activity in the second phase as well, which is thought to occur due to suppression of prostaglandins, kinins and proteases synthesis induced by carrageenan and egg albumin during this phase [62].”
Background
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“Both these structures are responsible for the awareness of pain, pain-related affective reactions (fear, aggression, anger) and the formation of pain-related behavioral models [8].”
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Best Practices in Management of Postpartum Pain
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Differential development of TRPV1-expressing sensory nerves in peripheral organs
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“In addition to opioids, a variety of neurotransmitters, modulators and their receptors have been implicated in the control of spinal nociceptive processing descending from the RVM (Julius and Basbaum 2001; Millan 2002).”
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Down-Regulation of Tumor-Associated NADH Oxidase, tNOX (ENOX2), Enhances Capsaicin-Induced Inhibition of Gastric Cancer Cell Growth
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“spinal cord and in trigeminal ganglia for the sensation of pain [49] and is activated by several noxious stimuli such as heat, voltage, and vanilloids.”
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“The ion channel activated by capsaicin, TRPV1, is a ligand-gated channel activated by noxious heat (P 43 C), low pH, and polyunsaturated fatty acids [46] and is essential for the development of inflammatory hyperalgesia [16,26].”
Background
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“It is believed that capsaicin directly activates a non-selective ionotropic channel in primary sensory neurons, the capsaicin receptor, also known as the transient receptor potential vanilloid 1 (TRPV1) (Calixto et al., 2005; Julius and Basbaum, 2001; Szallasi and Blumberg, 1999).”
Background
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“During tendinopathy, the inflammatory mediators play as a vital role in evoking pain via direct or indirect activation and sensitization of nociceptors [49].”
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“As with spinal sensory afferents [16,17], the ‘‘transient”
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“Among these are voltage-gated Ca 2+ channels (VGCCs) [17].”
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“Numerous studies have been suggested that release of ATP is closely related to SP (Julius and Basbaum, 2001; Sluka, 2002).”
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“, hot plate test) [46], the present findings seem to suggest the potential of MEMC as an antagonist of TRPV1 receptors at the peripheral and central levels.”
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“Journal of Pain Research 2012:5 proinflammatory cytokines, eg, tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-1β, can promote nociceptor hypersensitivity,(1,3,6) whereas other factors, such as anti-inflammatory cytokines, eg, IL-10 and IL-4, and endogenous opioids, can have the opposite effect on nociceptor…”
Painful prosthesis: approaching the patient with persistent pain following total hip and knee arthroplasty.
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“When these barriers are invaded with pathogens nociceptors are activated due to inflammation and tissue breakdown [5].”
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Targeting TRPV1 as an Alternative Approach to Narcotic Analgesics to Treat Chronic Pain Conditions
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“Peripheral sensitization is a phenomenon, which involves an increase in the responsiveness of nociceptive ion channels and a reduction in activation threshold of nociceptive neurons (19, 20 ).”
BackgroundInfluential

Authors: Julius, D., & Basbaum, A. I.
Affiliations: University of California, San Francisco (US)
Corresponding author: Julius, David
ORCID: Julius, David
Basbaum, Allan I.
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2001-09
Volume: 413
Issue: 6852
Pages: 203-210
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/35093019
OpenAlex: W1883044208
Cited by: 2,685
References: 73
Citations by year: 2026: 63 · 2025: 66 · 2024: 95 · 2023: 91 · 2022: 100 · 2021: 103 · 2020: 94 · 2019: 138 · 2018: 119 · 2017: 113 · 2016: 109 · 2015: 114 · 2014: 147 · 2013: 144 · 2012: 117
FWCI: 8.09
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
RePEc: Research Papers in Economics (submittedVersion)
Funders: Bristol-Myers Squibb
National Institutes of Health
National Institute of Mental Health
Topics: Health Sciences › Medicine › Physiology (medical) › Pain Mechanisms and Treatments
Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
Keywords: nociception, pain, chronic pain, primary sensory neurons, pain detection, thermal pain, mechanical pain, chemical pain, acute to chronic pain transition, pain signalling, molecular mechanisms
MeSH terms: Animals, Forecasting, Humans, Neurons, Afferent, Pain, Signal Transduction

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