The DOI matches its Crossref record; 75 of the 76 references it cites were found in a registry or an index.
Neuronal Plasticity: Increasing the Gain in Pain
Abstract
We describe those sensations that are unpleasant, intense, or distressing as painful. Pain is not homogeneous, however, and comprises three categories: physiological, inflammatory, and neuropathic pain. Multiple mechanisms contribute, each of which is subject to or an expression of neural plasticity-the capacity of neurons to change their function, chemical profile, or structure. Here, we develop a conceptual framework for the contribution of plasticity in primary sensory and dorsal horn neurons to the pathogenesis of pain, identifying distinct forms of plasticity, which we term activation, modulation, and modification, that by increasing gain, elicit pain hypersensitivity.
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“Sometimes, however, central neural processing can be 'modified' so that initially peripherally induced central sensitization becomes independent of peripheral sensitization”
From Chronic pelvic pain and endometriosis: translational evidence of the relationship and implications (2011) · cites this paper as Woolf and Salter, 2000
In the citing paper
“Central sensitization is initiated by peripheral sensitization (Fig. 1) and maintained by continued input to the CNS from sensitized sensory afferent fibers”
From Chronic pelvic pain and endometriosis: translational evidence of the relationship and implications (2011) · cites this paper as Woolf and Salter, 2000
In the citing paper
“Changes in activity of peripherally sensitized fibers, due to estradiol and sympathetic modulation in the rat model, can 'modulate' activity of centrally sensitized neurons to affect pain severity”
From Chronic pelvic pain and endometriosis: translational evidence of the relationship and implications (2011) · cites this paper as Woolf and Salter, 2000
In the citing paper
“Central pain sensitization (CPS) results from neuronal plasticity that involves structural and functional changes in the central nervous system (CNS).”
From Effectiveness of acceptance and commitment therapy in central pain sensitization syndromes: A systematic review (2021) · cites this paper as [1]
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“In addition to agents that can directly activate TRPV1, other factors such as bradykinin, ATP, and NGF can modulate TRPV1 function indirectly via activation of second-messenger signaling pathways (Woolf and Salter, 2000; Julius and Basbaum, 2001), resulting in TRPV1 sensitization.”
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“The alteration in gene expression and the resultant changes in the excitability of DRG neurons may be involved in peripheral and central sensitization in acute and chronic pain conditions (Dubner and Ruda, 1992; Woolf and Salter, 2000).”
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“Although the molecular and cellular mechanisms underlying the development and maintenance of chronic pain remain unclear, it is generally believed that chronic pain results from neural plasticity including peripheral sensitization([58-60]) (in primary sensory neurons) and central sensitization([39,61-65]) (in spinal c…”
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“BDNF may act as a modulator of synaptic transmission in the spinal dorsal horn (Snider and McMahon, 1998; Woolf and Salter, 2000), as found previously in the hippocampus (Canossa et al.”
BackgroundCentral sensitization: uncovering the relation between pain and plasticity.
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BackgroundInfluentialDisruption of Attention and Working Memory Traces in Individuals with Chronic Pain
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“Tissue levels of protons, inflammatory mediators (prostaglandins, bradykinin), growth factors (NGFs) and hormones (adrenaline) [30,62,63] all have been shown to influence sensory input to the nervous system.”
BackgroundMechanisms of migraine as a chronic evolutive condition
Andreou, A. P., & Edvinsson, L. I. (2019) · The Journal of Headache and Pain · doi:10.1186/s10194-019-1066-0 · Cited by 294
Microglia and neuropathic pain
Inoue, K., & Tsuda, M. (2009) · Glia · doi:10.1002/glia.20871 · Cited by 294
Central Sensitization and Altered Central Pain Processing in Chronic Low Back Pain
Roussel, N. A., Nijs, J., Meeus, M., Mylius, V., Fayt, C., & Oostendorp, R. A. B. (2013) · Clinical Journal of Pain · doi:10.1097/ajp.0b013e31826f9a71 · Cited by 301
The Pain of Tendinopathy: Physiological or Pathophysiological?
Rio, E., Moseley, G. L., Purdam, C. R., Samiric, T., Kidgell, D. J., Pearce, A. J., Jaberzadeh, S., & Cook, J. L. (2013) · Sports Medicine · doi:10.1007/s40279-013-0096-z · Cited by 303
“Tenderness and evoked pain that spread, in a nondermatomal, non-peripheral nerve distribution is best explained by central sensitisation [36].”
BackgroundSymptoms and signs in patients with suspected neuropathic pain
Rasmussen, P. V., Sindrup, S. H., Jensen, T. S., & Bach, F. W. (2004) · Pain · doi:10.1016/j.pain.2004.04.034 · Cited by 285
Miyoshi, K., Obata, K., Kondo, T., Okamura, H., & Noguchi, K. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.3512-08.2008 · Cited by 291
“Previous studies have focused considerable attention on the directly damaged primary afferents and their influence on the activity of spinal dorsal horn neurons (Woolf and Salter, 2000; Scholz and Woolf, 2002).”
BackgroundIt's time for change with the management of non-specific chronic low back pain
O’Sullivan, P. (2011) · British Journal of Sports Medicine · doi:10.1136/bjsm.2010.081638 · Cited by 284
Recent advances in postoperative pain management.
Vadivelu, N., Mitra, S., & Narayan, D. (2010) · PubMed Central · Cited by 284
Changes in cerebrospinal fluid levels of pro-inflammatory cytokines in CRPS
Alexander, G. M., van Rijn, M. A., van Hilten, J. J., Perreault, M. J., & Schwartzman, R. J. (2005) · Pain · doi:10.1016/j.pain.2005.04.013 · Cited by 280
Chronic pain following total hip arthroplasty: a nationwide questionnaire study
Nikolajsen, L., Brandsborg, B., Lucht, U., Jensen, T. S., & Kehlet, H. (2006) · Acta Anaesthesiologica Scandinavica · doi:10.1111/j.1399-6576.2006.00976.x · Cited by 279
“A series of experimental studies have shown that noxious stimuli may produce hyperexcitability and sensitization in second-order neurons in the central nervous system [for a review, see Woolf and Salter (20)].”
BackgroundDREAM Is a Critical Transcriptional Repressor for Pain Modulation
Cheng, H. M., Pitcher, G. M., Laviolette, S. R., Whishaw, I. Q., Tong, K. I., Kockeritz, L. K., Wada, T., Joza, N. A., Crackower, M. A., Gonçalves, J., et al. (2002) · Cell · doi:10.1016/s0092-8674(01)00629-8 · Cited by 275
“Despite recent advances in our understanding 610 University Avenue of pain mechanisms (Woolf and Salter, 2000), the satisToronto, Ontario M5G 2M9 factory management of pathologic pain eludes current Canada treatment strategies.”
BackgroundP2Y12Receptor Upregulation in Activated Microglia Is a Gateway of p38 Signaling and Neuropathic Pain
Kobayashi, K., Yamanaka, H., Fukuoka, T., Dai, Y., Obata, K., & Noguchi, K. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.5589-07.2008 · Cited by 275
“Injury to the peripheral nerve is known to induce the variety of changes in intracellular signaling molecules and gene expression in the spinal cord (Woolf and Salter, 2000; Scholz and Woolf, 2002; Obata and Noguchi, 2004; Zhuang et al., 2006).”
BackgroundBaba, H., Ji, R., Kohno, T., Moore, K. A., Ataka, T., Wakai, A., Okamoto, M., & Woolf, C. J. (2003) · Molecular and Cellular Neuroscience · doi:10.1016/s1044-7431(03)00236-7 · Cited by 274
Peripheral mechanisms of pain and analgesia
Stein, C., Clark, J. D., Oh, U., Vasko, M. R., Wilcox, G. L., Overland, A. C., Vanderah, T. W., & Spencer, R. H. (2009) · Brain Research Reviews · doi:10.1016/j.brainresrev.2008.12.017 · Cited by 277
“After synaptic transmission and modulation within the primary sensory neuron and spinal cord, nociceptive signals reach the brain, where they are finally perceived as “pain”, within the context of cognitive and environmental factors (Woolf and Salter, 2000).”
NIH Consensus Statement on Total Knee Replacement December 8-10, 2003*
Ekman, E. F., & Koman, L. A. (2004) · Journal of Bone and Joint Surgery · doi:10.2106/00004623-200406000-00030 · Cited by 270
‘Protective premedication’: an option with gabapentin and related drugs?
Dahl, J. B., Mathiesen, O., & Møiniche, S. (2004) · Acta Anaesthesiologica Scandinavica · doi:10.1111/j.1399-6576.2004.00484.x · Cited by 269
“This is mediated by a decrease in inhibitory input or an increase in synaptic efficacy or membrane excitability, triggered by wind-up, neurokinin and N-methyl-D-aspartic acid (NMDA)receptor mechanisms (1, 3).”
BackgroundGlial activation and pathological pain
Wieseler‐Frank, J., Maier, S. F., & Watkins, L. R. (2004) · Neurochemistry International · doi:10.1016/j.neuint.2003.09.009 · Cited by 267
Book Review: The Neurobiology of Pain: Developmental Aspects
Fitzgerald, M., & Beggs, S. (2001) · The Neuroscientist · doi:10.1177/107385840100700309 · Cited by 264
Prevalence of chronic pain seven years following limb threatening lower extremity trauma ☆
Castillo, R. C., MacKenzie, E. J., Wegener, S. T., & Bosse, M. J. (2006) · Pain · doi:10.1016/j.pain.2006.04.020 · Cited by 265
Neuropathic pain symptoms in a community knee OA cohort
Hochman, J. R., Gagliese, L., Davis, A. M., & HAWKER, G. A. (2011) · Osteoarthritis and Cartilage · doi:10.1016/j.joca.2011.03.007 · Cited by 264
Gabapentin: a multimodal perioperative drug?
Kong, V. K., & Irwin, M. G. (2007) · British Journal of Anaesthesia · doi:10.1093/bja/aem316 · Cited by 263
Fine, P. G. (2011) · Pain Medicine · doi:10.1111/j.1526-4637.2011.01187.x · Cited by 314
Keller, A. F., Beggs, S., Salter, M. W., & Koninck, Y. D. (2007) · Molecular Pain · doi:10.1186/1744-8069-3-27 · Cited by 278
“Several cellular substrates for these symptoms have been proposed [3], including suppression of the inhibition mediated by GABAA- and glycine receptors in the dorsal horn of the spinal cord [4-6].”
BackgroundA Novel Tool for the Assessment of Pain: Validation in Low Back Pain
Scholz, J., Mannion, R., Hord, E. D., Griffin, R. S., Rawal, B., Zheng, H., Scoffings, D. J., Phillips, A., Guo, J., Laing, R. J. C., et al. (2009) · PLoS Medicine · doi:10.1371/journal.pmed.1000047 · Cited by 263
“As a result, normally innocuous stimuli now produce pain (allodynia), and an area of heightened pain sensitivity (hyperalgesia) expands beyond the site of the inflammation [2,9].”
BackgroundBurian, M., & Geißlinger, G. (2005) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2005.02.004 · Cited by 259
“Both phenomena are an expression of neural plasticity which is a response of the nervous system to the peripheral tissue injury and inflammation (Woolf & Salter, 2000).”
BackgroundRomero, L. M., & Remage‐Healey, L. (2000) · General and Comparative Endocrinology · doi:10.1006/gcen.2000.7491 · Cited by 259
Only Half of the Chronic Pain After Thoracic Surgery Shows a Neuropathic Component
Steegers, M. A. H., Snik, D. M., Verhagen, A. F. T. M., van der Drift, M. A., & Wilder‐Smith, O. H. G. (2008) · Journal of Pain · doi:10.1016/j.jpain.2008.05.009 · Cited by 258
Neuronal and microglial mechanisms of neuropathic pain
Zhuo, M., Wu, G., & Wu, L. (2011) · Molecular Brain · doi:10.1186/1756-6606-4-31 · Cited by 256
“The activation of NMDA receptors would allow Ca influx, which in turn activates calcium-sensitive intracellular signal cascades that lead to the phosphorylation of the NMDA receptor and other receptor-ion channels, initiating prolonged increases in the excitability of spinal cord neurons [12].”
BackgroundWang, H., Sun, H., Penna, K. B. D., Benz, R., Xu, J., Gerhold, D. L., Holder, D., & Koblan, K. S. (2002) · Neuroscience · doi:10.1016/s0306-4522(02)00341-x · Cited by 256
Metadata
- Authors
- Woolf, C. J., & Salter, M. W.
- Affiliations
- Harvard University (US)
- University of Toronto (CA)
- Corresponding author
- Woolf, Clifford J.
- Venue
- Science
- Published
- 2000-06-09
- Volume
- 288
- Issue
- 5472
- Pages
- 1765-1768
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2133316133
- Cited by
- 3,781
- References
- 76
- Citations by year
- 2026: 62 · 2025: 101 · 2024: 96 · 2023: 104 · 2022: 99 · 2021: 99 · 2020: 129 · 2019: 112 · 2018: 124 · 2017: 140 · 2016: 150 · 2015: 170 · 2014: 142 · 2013: 188 · 2012: 166
- FWCI
- 13.94
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology (medical) › Pain Mechanisms and Treatments
- Health Sciences › Medicine › Anesthesiology and Pain Medicine › Pain Management and Treatment
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- neuroplasticity, pain, hyperalgesia, primary sensory neurons, dorsal horn neurons, neuropathic pain, inflammatory pain, plasticity mechanisms, pain modulation
- MeSH terms
- Animals, Humans, Inflammation, Models, Neurological, Synaptic Transmission, Neuronal Plasticity, Neurons, Afferent, Nociceptors, Pain, Signal Transduction, Posterior Horn Cells, Peripheral Nerve Injuries
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