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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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Xiao, H., Huang, Q., Zhang, F., Bao, L., Lu, Y., Guo, C., Yang, L., Huang, W.-J., Fu, G., Xu, S., et al. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.122231899 · Cited by 501
Nikolajsen, L., & Jensen, T. S. (2001) · British Journal of Anaesthesia · doi:10.1093/bja/87.1.107 · Cited by 493
Exercise-induced immune system response: Anti-inflammatory status on peripheral and central organs
Scheffer, D. D. L., & Latini, A. (2020) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2020.165823 · Cited by 535
Glial–Cytokine–Neuronal Interactions Underlying the Mechanisms of Persistent Pain
Guo, W., Wang, H., Watanabe, M., Shimizu, K., Zou, S., LaGraize, S. C., Wei, F., Dubner, R. A., & Ren, K. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.0176-07.2007 · Cited by 480
“NMDARs are prominently involved in activity-dependent synaptic plasticity and persistent pain (Ren and Dubner, 1999; Woolf and Salter, 2000).”
BackgroundMolecular mechanisms of cancer pain
Mantyh, P. W., Clohisy, D. R., Koltzenburg, M., & Hunt, S. (2002) · Nature reviews. Cancer · doi:10.1038/nrc747 · Cited by 492
“After tissue injury, many nociceptors alter their patterns of signalling-peptide and growth-factor expressio”
BackgroundWhen does acute pain become chronic?
Voscopoulos, C., & Lema, M. (2010) · British Journal of Anaesthesia · doi:10.1093/bja/aeq323 · Cited by 473
Translation of symptoms and signs into mechanisms in neuropathic pain
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Evidence for spinal cord hypersensitivity in chronic pain after whiplash injury and in fibromyalgia
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Ji, R., Befort, K., Brenner, G. J., & Woolf, C. J. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-02-00478.2002 · Cited by 466
“The increased neuronal excitability appears to result from post-translational regulation, such as phosphorylation, of key membrane receptors and channels (Woolf and Salter, 2000; Ji and Woolf, 2001).”
BackgroundThe Symptoms of Osteoarthritis and the Genesis of Pain
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Neuropathic pain: a practical guide for the clinician
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“, more likely to transmit pain to the brain).(63) This can manifest in expansion of the affected area, increased response to painful inputs and transmission of pain following nonpainful stimuli.”
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“…central neural processing can be ‘modified’ so that initially peripherally induced central sensitization becomes independent of peripheral sensitization (Woolf and Salter, 2000) via neural mechanisms similar to those underlying memory (Melzack et al., 2001; Ji et al., 2003a; Ren and Dubner, 2007).”
BackgroundReactive oxygen species (ROS) play an important role in a rat model of neuropathic pain
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“gif" NDATA ITEM> ]> The long-term increase in pain sensitivity frequently seen after injury is thought to be due to (i) alterations in synaptic transmission and morphology within the spinal cord and (ii) changes in descending controls from the brainste”
BackgroundMorphine hyperalgesia gated through microglia-mediated disruption of neuronal Cl− homeostasis
Ferrini, F., Trang, T., Mattioli, T.-A. M., Laffray, S., Del’Guidice, T., Lorenzo, L.-É., Castonguay, A., Doyon, N., Zhang, W., Godin, A. G., et al. (2013) · Nature Neuroscience · doi:10.1038/nn.3295 · Cited by 441
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The whole body receptive field of dorsal horn multireceptive neurones
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Perioperative ketamine for acute postoperative pain
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RetractedReversal of pathological pain through specific spinal GABAA receptor subtypes
Knabl, J., Witschi, R., Hösl, K., Reinold, H., Zeilhofer, U. B., Ahmadi, S., Brockhaus, J., Sergejeva, M., Hess, A., Brune, K., et al. (2008) · Nature · doi:10.1038/nature06493 · Cited by 438
PSA-NCAM in mammalian structural plasticity and neurogenesis
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Scholz, J., Broom, D. C., Youn, D. H., Mills, C. D., Kohno, T., Suter, M. R., Moore, K. A., Décosterd, I., Coggeshall, R. E., & Woolf, C. J. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.1526-05.2005 · Cited by 437
“These include afferent activity-evoked central sensitization (Woolf and Salter, 2000), microglia activation (Tsuda et al., 2005), and altered modulation of sensory transmission by pathways descending from the brainstem (Mantyh and Hunt, 2004; Suzuki et al., 2004).”
Background
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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