Cited by 3,781Pain Mechanisms and TreatmentsPain Management and TreatmentNeuroscience and Neuropharmacology Research

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Neuronal Plasticity: Increasing the Gain in Pain

Woolf, Clifford J., Salter, Michael W.·2000·Science

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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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Crossref · 10.1126/science.288.5472.1765

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The development and maintenance of human visceral pain hypersensitivity is dependent on the N-methyl-d-aspartate receptor
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Targeting the Microglial Signaling Pathways: New Insights in the Modulation of Neuropathic Pain
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The AMPA Receptor Subunits GluR-A and GluR-B Reciprocally Modulate Spinal Synaptic Plasticity and Inflammatory Pain
Hartmann, B., Ahmadi, S., Heppenstall, P. A., Lewin, G. R., Schott, C., Borchardt, T., Seeburg, P. H., Zeilhofer, H. U., Sprengel, R., & Kuner, R. (2004) · Neuron · doi:10.1016/j.neuron.2004.10.029 · Cited by 201
“, 1999), their net contribuvelop following peripheral tissue injury (Woolf and Salter, 2000).”
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Changes in brain gray matter due to repetitive painful stimulation
Teutsch, S., Herken, W., Bingel, U., Schoell, E. D., & May, A. (2008) · NeuroImage · doi:10.1016/j.neuroimage.2008.05.044 · Cited by 202
“Chronic pain is endogenous, probably produced by reorganization and dynamic interaction among nociceptors (Woolf and Salter, 2000), neurotransmitters (Koltzenburg, 1999), glial, neuronal and endothelial cells (Gordh et al., 2006), receptive fields (Suzuki et al., 2000) and the immune system…”
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Targeting the NMDA Receptor Subunit NR2B for the Treatment of Neuropathic Pain
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“This fits with the notion that prolonged nociceptive input may lead to CS and features of NP in OA (7).”
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“This process has been well established and referred to as peripheral neural plasticity or sensitization (Woolf and Salter, 2000; Julius and Basbaum, 2001).”
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Amantadine in a Multimodal Analgesic Regimen for Alleviation of Refractory Osteoarthritis Pain in Dogs
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“One hypothesis is that gray matter abnormalities seen in chronic pain patients represent the neuroplastic ‘‘chronification” [51] or ‘‘learning” [2] of pain.”
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Migraine: New Molecular Mechanisms
Pietrobon, D. (2005) · The Neuroscientist · doi:10.1177/1073858405275554 · Cited by 194
Mechanisms of Cardiac Pain
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“In the past few decades, there has been a substantial improvement in the understanding of the mechanism of surgical pain (48-50).”
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A Sub‐10 nm Vertical Organic/Inorganic Hybrid Transistor for Pain‐Perceptual and Sensitization‐Regulated Nociceptor Emulation
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Brain activity for spontaneous pain of postherpetic neuralgia and its modulation by lidocaine patch therapy
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The neurobiology of skeletal pain
Mantyh, P. W. (2014) · European Journal of Neuroscience · doi:10.1111/ejn.12462 · Cited by 195
The Central Sensitization Inventory validated and adapted for a Brazilian population: psychometric properties and its relationship with brain-derived neurotrophic factor
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“6,7 This syndrome comprises impaired functioning of neurons and circuits in nociceptive pathways, increased membrane excitability and synaptic efficacy, and reduced inhibition.”
A Conditional Deletion of the NR1 Subunit of the NMDA Receptor in Adult Spinal Cord Dorsal Horn Reduces NMDA Currents and Injury-Induced Pain
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“Central sensitization results in increased synaptic efficacy, and the recruitment of normally subliminal inputs leads to the spread of pain sensitivity beyond the site of injury (secondary hyperalgesia) and the generation of pain in response to low-threshold inputs (allodynia) (Woolf and Salter, 2000).”
BackgroundInfluential
Pain hypersensitivity mechanisms at a glance
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Corneal Pain without Stain: Is it Real?
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Selective Inflammatory Pain Insensitivity in the African Naked Mole-Rat (Heterocephalus glaber)
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Peripheral Nerve Injury and TRPV1-Expressing Primary Afferent C-Fibers Cause Opening of the Blood-Brain Barrier
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Modulation of Peripheral Sensory Neurons by the Immune System: Implications for Pain Therapy
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“” After modulation within the primary afferent neurons 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).”
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The psychology of chronic post-surgical pain: new frontiers in risk factor identification, prevention and management
Weinrib, A. Z., Azam, M. A., Birnie, K. A., Burns, L. C., Clarke, H., & Katz, J. (2017) · British Journal of Pain · doi:10.1177/2049463717720636 · Cited by 178
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Background
Peripheral and central mechanisms of visceral sensitization in man
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Authors: Woolf, C. J., & Salter, M. W.
Affiliations: Harvard University (US)
University of Toronto (CA)
Corresponding author: Woolf, Clifford J.
ORCID: Woolf, Clifford J.
Salter, Michael W.
Venue: Science
Publisher: American Association for the Advancement of Science (AAAS)
Published: 2000-06-09
Volume: 288
Issue: 5472
Pages: 1765-1768
ISSN: 0036-8075 (ISSN-L)
1095-9203
DOI: 10.1126/science.288.5472.1765
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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Neuronal Plasticity: Increasing the Gain in Pain

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