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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“By increasing the gain of sensory inputs through presynaptic facilitation of glutamate re - lease ( Woolf and Salter , 2000 ) , thermal sensation may be affected by menthol , its derivatives , and menthol - like endogenous ligands .”
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Low-frequency BOLD fluctuations demonstrate altered thalamocortical connectivity in diabetic neuropathic pain
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Reduction of Anion Reversal Potential Subverts the Inhibitory Control of Firing Rate in Spinal Lamina I Neurons: Towards a Biophysical Basis for Neuropathic pain
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Retigabine: Chemical Synthesis to Clinical Application
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The common link between functional somatic syndromes may be central sensitisation
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Effects of the N-Methyl-D-Aspartate Receptor Antagonist Dextromethorphan on Temporal Summation of Pain are Similar in Fibromyalgia Patients and Normal Control Subjects
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Functional urological disorders: a sensitized defence response in the bladder–gut–brain axis
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Pain in the brain: are hormones to blame?
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Analgesic effect of vitamin E is mediated by reducing central sensitization in neuropathic pain
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Sublingual Buprenorphine Is Effective in the Treatment of Chronic Pain Syndrome
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Prevention of chronic postoperative pain: Cellular, molecular, and clinical insights for mechanism-based treatment approaches
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An ACC–VTA–ACC positive-feedback loop mediates the persistence of neuropathic pain and emotional consequences
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Influential
Nitrous Oxide Revisited
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“Because the 50/50% N2O–O2 treatment did not induce any reduction of carrageenan-induced hind paw inflammation, this effect suggests that the pharmacologic effect of nitrous oxide is not limited to its antinociceptive effect during exposure but might also partially oppose mechanisms of pain sensitization initiated by t…”
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Glia in pathological pain: A role for fractalkine
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Spinal Protein Kinase M ζ Underlies the Maintenance Mechanism of Persistent Nociceptive Sensitization
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“Synaptic long-term potentiation (LTP) in nociceptive neurons of the dorsal horn closely resembles mechanisms underlying memory trace formation in other CNS structures (Woolf and Salter, 2000; Ji et al., 2003; Ikeda et al., 2006) and may represent a key point of intervention for preventing the expression of persistent…”
Background
Animal models of migraine: looking at the component parts of a complex disorder
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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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