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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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“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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Selective Blockade of the Capsaicin Receptor TRPV1 Attenuates Bone Cancer Pain
Ghilardi, J. R., Röhrich, H., Lindsay, T. H., Sevcik, M. A., Schwei, M. J., Kubota, K., Halvorson, K. G., Poblete, J., Chaplan, S. R., Dubin, A. E., et al. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.3815-04.2005 · Cited by 384
“…- 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
Brooks, J. C. W., & Tracey, I. (2005) · Journal of Anatomy · doi:10.1111/j.1469-7580.2005.00428.x · Cited by 400
“…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
Allegri, M., Montella, S., Salici, F., Valente, A., Marchesini, M., Compagnone, C., Baciarello, M., Manferdini, M. E., & Fanelli, G. C. (2016) · F1000Research · doi:10.12688/f1000research.8105.2 · Cited by 378
“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 .”
BackgroundCutaneous TRPV1+ Neurons Trigger Protective Innate Type 17 Anticipatory Immunity
Cohen, J. A., Edwards, T. N., Liu, A. W., Hirai, T., Jones, M. R., Wu, J., Li, Y., Zhang, S., Ho, J., Davis, B. M., et al. (2019) · Cell · doi:10.1016/j.cell.2019.06.022 · Cited by 388
White, F. A., Sun, J., Waters, S. M., Ma, C., Ren, D., Ripsch, M. S., Steflik, J., Cortright, D. N., LaMotte, R. H., & Miller, R. J. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0503496102 · Cited by 374
Brain Morphological Signatures for Chronic Pain
Baliki, M. N., Schnitzer, T. J., Bauer, W. R., & Apkarian, A. V. (2011) · PLoS ONE · doi:10.1371/journal.pone.0026010 · Cited by 390
“Thus, we can conclude that living with distinct chronic pain conditions confers a brain anatomical network reorganization, reflecting at least in part a physiological reorganization, that must be the result of the sum total of experiential changes (coping and suffering that result in novel associations and deficits in…”
BackgroundCell Signaling and the Genesis of Neuropathic Pain
Ji, R., & Strichartz, G. R. (2004) · Science s STKE · doi:10.1126/stke.2522004re14 · Cited by 372
Breaking barriers to novel analgesic drug development
Yekkirala, A. S., Roberson, D. P., Bean, B. P., & Woolf, C. J. (2017) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2017.87 · Cited by 370
MAPK activation in nociceptive neurons and pain hypersensitivity
Obata, K., & Noguchi, K. (2004) · Life Sciences · doi:10.1016/j.lfs.2004.01.007 · Cited by 359
“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 359
Dai, Y., Iwata, K., Fukuoka, T., Kondo, E., Tokunaga, A., Yamanaka, H., Tachibana, T., Liu, Y., & Noguchi, K. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-17-07737.2002 · Cited by 356
Adenosine in the spinal cord and periphery: release and regulation of pain
Sawynok, J., & Liu, X. J. (2003) · Progress in Neurobiology · doi:10.1016/s0301-0082(03)00050-9 · Cited by 355
Pain and Nociception: Mechanisms of Cancer-Induced Bone Pain
Falk, S., & Dickenson, A. H. (2014) · Journal of Clinical Oncology · doi:10.1200/jco.2013.51.7219 · Cited by 352
Yang, D., Luo, Z., Ma, S., Wong, W. T., Ma, L., Zhong, J., He, H., Zhao, Z., Cao, T., Yan, Z., et al. (2010) · Cell Metabolism · doi:10.1016/j.cmet.2010.05.015 · Cited by 351
“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
“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
Ji, R., Xu, Z., Strichartz, G. R., & Serhan, C. N. (2011) · Trends in Neurosciences · doi:10.1016/j.tins.2011.08.005 · Cited by 345
Lessons from peppers and peppermint: the molecular logic of thermosensation
Jordt, S., McKemy, D. D., & Julius, D. J. (2003) · Current Opinion in Neurobiology · doi:10.1016/s0959-4388(03)00101-6 · Cited by 343
Self-citationChuang, H.-H., Neuhausser, W., & Julius, D. J. (2004) · Neuron · doi:10.1016/j.neuron.2004.08.038 · Cited by 338
Self-citationChen, C.-L., Broom, D. C., Liu, Y., de Nooij, J. C., Li, Z., Cen, C., Samad, O. A., Jessell, T. M., Woolf, C. J., & Ma, Q. (2006) · Neuron · doi:10.1016/j.neuron.2005.10.036 · Cited by 339
“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
Bourinet, E., Altier, C., Hildebrand, M. E., Trang, T., Salter, M. W., & Zamponi, G. W. (2014) · Physiological Reviews · doi:10.1152/physrev.00023.2013 · Cited by 349
LPS Sensitizes TRPV1 via Activation of TLR4 in Trigeminal Sensory Neurons
Diogenes, A. R., Ferraz, C. C. R., Akopian, A. N., Henry, M. A., & Hargreaves, K. (2011) · Journal of Dental Research · doi:10.1177/0022034511400225 · Cited by 337
“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
Visualizing Cold Spots: TRPM8-Expressing Sensory Neurons and Their Projections
Dhaka, A. K., Earley, T. J., Watson, J., & Patapoutian, A. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.3976-07.2008 · Cited by 333
“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
Vardeh, D., Mannion, R., & Woolf, C. J. (2016) · Journal of Pain · doi:10.1016/j.jpain.2016.03.001 · Cited by 339
Bohlen, C. J., Priel, A., Zhou, S., King, D., Siemens, J., & Julius, D. J. (2010) · Cell · doi:10.1016/j.cell.2010.03.052 · Cited by 312
“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 315
“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].”
BackgroundAmaya, F., Wang, H., Costigan, M., Allchorne, A. J., Hatcher, J. P., Egerton, J., Stean, T. O., Morisset, V., Grose, D., Gunthorpe, M. J., et al. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.4015-06.2006 · Cited by 302
“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
Metadata
- 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 (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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