Molecular mechanisms of nociception
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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It is possible that a ZnIUD would cause users less pain and bleeding compared to the CuIUD, due to the absence of localised inflammation.
“Therefore, it is possible that a ZnIUD would cause users less pain and bleeding compared to the CuIUD, due to the absence of localised inflammation (24,25).”
From Zinc as a non-hormonal contraceptive: a better alternative to the copper intrauterine device (IUD) (2022) · cites this paper as [24]
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“VR-1 receptors are sensitive to capsaicin, and their physiological role is sensing thermal stimuli [81].”
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“C-fiber nociceptors locally produce CGRP and Substance P upon activation by these stressors, and these neuropeptides coordinate local stress adaptations known as neuro-inflammation (Julius and Basbaum, 2001).”
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Nociceptors Are Interleukin-1β Sensors
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“Nociceptor activators, the external stimuli that drive this pain, act on specific high threshold heat-, mechanical- or chemicalsensitive ion channel transducers expressed by the nociceptors, to produce inward currents in their peripheral terminals (Julius and Basbaum, 2001).”
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“peripheral, spinal and cerebral nervous system [25,40,50,80].”
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“The specificity of putative TRPV1 actions beyond primary sensory neurons, where its expression levels are by far the highes”
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Resolvins RvE1 and RvD1 attenuate inflammatory pain via central and peripheral actions
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“…both pharmacological and electrophysicological approaches (Bodnar et al., 1991; Morgan et al., 1992; Kiefel et al., 1993; Rossi et al., 1993, 1994b; Gutstein et al., 1998; Mitchell et al., 1998; Fields and Martin, 2001; Julius and Basbaum, 2001; Basbaum and Julius, 2006; Basbaum et al., 2009).”
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“robust or dramatic (Figure 4). Since many inflammatory factors activating PLC-coupled receptors are involved in the inflammatory response [ 47 ,48].”
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Pharmacological blockade of the vanilloid receptor TRPV1 elicits marked hyperthermia in humans
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“7), capsaicin, resiniferatoxin, components of the ‘‘inflammatory soup,” products of lipoxygenase, and G-protein coupled receptor signaling, making it a molecular integrator of pain transduction [1,14,17,29].”
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The emergence of transcriptional identity in somatosensory neurons
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“And, indeed, nociceptive neurons of varying subtypes are differentiated by histological, electrophysiological, and molecular characteristics (Julius and Basbaum, 2001).”
BackgroundPain and immunity: implications for host defence
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Molecular basis of infrared detection by snakes
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Self-citationThe Cell and Molecular Basis of Mechanical, Cold, and Inflammatory Pain
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Molecular mechanisms of cancer pain
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“Recent work has shown that specific sets of ion channels and transmembrane receptors appear largely confined to primary afferent neurons where they likely contribute to the detection and transmission of differ- ent kinds of nociceptive stimuli (Julius and Basbaum, 2001).”
BackgroundPeripheral thermosensation in mammals
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“Although glutamate is the major excitatory neurotransmitter of all primary afferents, the C nociceptors can also be subdivided into an NGF/TrkA-dependent, peptidergic population and a GDNF/cRet-dependent, nonpeptidergic subset (Julius and Basbaum, 2001; Snider and McMahon, 1998).”
BackgroundSelf-citationCancer pain and its impact on diagnosis, survival and quality of life
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TREK‐1, a K+ channel involved in polymodal pain perception
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“…especially in relation with TRPV1, an Naþ and Ca2þ permeable channel expressed in small diameter DRG neurons associated with the detection of noxious heat (Caterina et al, 1997; Julius and Basbaum, 2001) and activated by the noxious ligand capsaicin (Caterina et al, 1997; Voets et al, 2004).”
BackgroundInfluentialRegulated Exocytosis Contributes to Protein Kinase C Potentiation of Vanilloid Receptor Activity
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Targeting Astrocyte Signaling for Chronic Pain
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“, substance P and calcitonin gene-related peptide), which are released from the primary afferents.(1) The information is further relayed to the thalamus, and it finally reaches the parietal lobe of the cerebral cortex for pain perception.”
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“Capsaicin activates C-fibers via the TRPV1 channel, producing inflammation and hyperalgesia (Julius and Basbaum, 2001).”
BackgroundNasal chemosensory cells use bitter taste signaling to detect irritants and bacterial signals
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“) and TrpM8 (mints) (21, 22) as well as ASICs (for responsiveness to acids).”
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The mechano‐activated K+ channels TRAAK and TREK‐1 control both warm and cold perception
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“Identification of ion channels involved in peripheral nociceptor activation is essential to our understanding of mechanisms of pain perception (Julius and Basbaum, 2001; Abrahamsen et al, 2008).”
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Selective Blockade of the Capsaicin Receptor TRPV1 Attenuates Bone Cancer Pain
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“…- induced pain behaviors is that other receptors ( such as bradykinin , P2X 3 , and prostaglandin receptors , or acid - sensing ion channel 3 and voltage - gated sodium channels ) may also be involved in the generation and maintenance of this pain state ( Julius and Basbaum , 2001 ; Mantyh et al .”
BackgroundSelf-citationREVIEW: From nociception to pain perception: imaging the spinal and supraspinal pathways
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“…classification of peripheral nociceptors, there have been considerable advances recently in our understanding of the molecular basis of nociception (Hunt & Mantyh, 2001; Julius & Basbaum, 2001) and thermosensation (Cesare et al. 1999; Peier et al. 2002; Jordt et al. 2003; Patapoutian et al. 2003).”
BackgroundMechanisms of low back pain: a guide for diagnosis and therapy
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“The spinal dorsal horn is a major site of integration of somatosensory information and is composed of several interneuron populations forming descending inhibitory and facilitatory pathways, able to modulate the transmission of nociceptive signals 35 .”
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BackgroundCell Signaling and the Genesis of Neuropathic Pain
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“Neuronal plasticity occurs in primary afferent neurons, as well as spinal dorsal horn neurons (Woolf and Costigan, 1999; Woolf and Salter, 2000; Julius and Basbaum, 2001; Scholz and Woolf, 2002).”
BackgroundMolecular Determinants of Vanilloid Sensitivity in TRPV1
Gavva, N. R., Klionsky, L., Qu, Y., Shi, L., Tamir, R., Edenson, S., Zhang, T. J., Viswanadhan, V. N., Tóth, A., Pearce, L. V., et al. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m312577200 · Cited by 356 · see citing works
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Adenosine in the spinal cord and periphery: release and regulation of pain
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Pain and Nociception: Mechanisms of Cancer-Induced Bone Pain
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“TRPV1 activation in sensory neurons causes nociception (Julius and Basbaum, 2001).”
BackgroundAntinociceptive and Antioxidant Activities of Phytol In Vivo and In Vitro Models
Bertozzo, C. C. D. M. S., Salvadori, M. G. D. S. S., Mota, V. G., Costa, L. M., de Almeida, A. A. C., de Oliveira, G. A. L., Costa, J. P., de Sousa, D. P., de Freitas, R. M., & de Almeida, R. N. (2013) · Neuroscience Journal · doi:10.1155/2013/949452 · Cited by 346 · see citing works
“This method, first described by Woolfe and Macdonald [34], consists of quantifying the reaction time to the thermal stimulus caused by a plate heated to a temperature of 53 ± 1C, based on a pain threshold that, depending on the type of fiber, ranges from 43 to 53C [3].”
BackgroundMethodEmerging roles of resolvins in the resolution of inflammation and pain
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Lessons from peppers and peppermint: the molecular logic of thermosensation
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“Loss of Nociceptive Ion Channels and Sensory Receptors in Runx1 Mice The expression of high threshold ion channels defines the specialized peripheral receptive properties of nociceptor subclasses (Hunt and Mantyh, 2001; Jordt et al., 2003; Julius and Basbaum, 2001; Lewin et al., 2004; Patapoutian et al., 2003; Wood, 2…”
BackgroundInfluentialCalcium-Permeable Ion Channels in Pain Signaling
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LPS Sensitizes TRPV1 via Activation of TLR4 in Trigeminal Sensory Neurons
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“The traditional hypothesis for pain associated with bacterial infections includes sensitization and activation of nociceptors by inflammatory mediators released from immune cells in response to the presence of bacteria or their constituents and toxins (Cunha et al., 1992; Julius and Basbaum, 2001).”
BackgroundA review of hyperacusis and future directions: Part I. Definitions and manifestations
Tyler, R. S., Pienkowski, M., Roncancio, E. R., Jun, H. J., Brozoski, T., Dauman, N., Coelho, C. B., Andersson, G., Keiner, A. J., Cacace, A. T., et al. (2014) · American Journal of Audiology · doi:10.1044/2014_aja-14-0010 · Cited by 329 · see citing works
Visualizing Cold Spots: TRPM8-Expressing Sensory Neurons and Their Projections
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“There are at least three classes of unmyelinated sensory neurons, which can be differentiated based on their growth factor dependence (Snider and McMahon, 1998; Julius and Basbaum, 2001): thermosensitive and peptidergic nociceptive neurons, which are dependent on NGF/TrkA signaling for survival, and nonpeptidergic noc…”
BackgroundToward a Mechanism-Based Approach to Pain Diagnosis
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“Chief among these is TRPV1, which is activated by capsaicin (the main pungent ingredient in ‘‘hot’’ chili peppers), extracellular protons, and other inflammation agents, as well as noxious heat (>43 C) (Julius and Basbaum, 2001).”
BackgroundSelf-citationBone cancer pain: Causes, consequences, and therapeutic opportunities
Mantyh, P. W. (2013) · Pain · doi:10.1016/j.pain.2013.07.044 · Cited by 307 · see citing works
“Both cancer cells and their associated stromal cells secrete a wide variety of factors [44,56], many of which have previously been shown to sensitize or directly excite primary afferent neurons [45].”
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“Conversion of the stimuli into ion fluxes across nociceptor membranes is mediated by high-threshold thermal, mechanical, and chemical protein transducers (Julius and Basbaum, 2001).”
Background
- Authors
- Julius, D., & Basbaum, A. I.
- Affiliations
- University of California, San Francisco (US)
- Corresponding author
- Julius, David
- Venue
- Nature
- Published
- 2001-09
- Volume
- 413
- Issue
- 6852
- Pages
- 203-210
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- 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 › 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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