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Central Sensitization: A Generator of Pain Hypersensitivity by Central Neural Plasticity

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Latremoliere, Alban, Woolf, Clifford J.·2009·The Journal of Pain

DOI 10.1016/j.jpain.2009.06.012PMC PMC2750819

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Abstract

Unlabelled Central sensitization represents an enhancement in the function of neurons and circuits in nociceptive pathways caused by increases in membrane excitability and synaptic efficacy as well as to reduced inhibition and is a manifestation of the remarkable plasticity of the somatosensory nervous system in response to activity, inflammation, and neural injury. The net effect of central sensitization is to recruit previously subthreshold synaptic inputs to nociceptive neurons, generating an increased or augmented action potential output: a state of facilitation, potentiation, augmentation, or amplification. Central sensitization is responsible for many of the temporal, spatial, and threshold changes in pain sensibility in acute and chronic clinical pain settings and exemplifies the fundamental contribution of the central nervous system to the generation of pain hypersensitivity. Because central sensitization results from changes in the properties of neurons in the central nervous system, the pain is no longer coupled, as acute nociceptive pain is, to the presence, intensity, or duration of noxious peripheral stimuli. Instead, central sensitization produces pain hypersensitivity by changing the sensory response elicited by normal inputs, including those that usually evoke innocuous sensations.Perspective In this article, we review the major triggers that initiate and maintain central sensitization in healthy individuals in response to nociceptor input and in patients with inflammatory and neuropathic pain, emphasizing the fundamental contribution and multiple mechanisms of synaptic plasticity caused by changes in the density, nature, and properties of ionotropic and metabotropic glutamate receptors.

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Authors: Latremoliere, A., & Woolf, C. J.
Affiliations: Harvard University (US)
Corresponding author: Woolf, Clifford J.
ORCID: Woolf, Clifford J.
Venue: The Journal of Pain
Publisher: Elsevier BV
Published: 2009-09
Volume: 10
Issue: 9
Pages: 895-926
ISSN: 1526-5900 (ISSN-L)
DOI: 10.1016/j.jpain.2009.06.012
PMC: PMC2750819
OpenAlex: W2155524482
Cited by: 3,913
References: 416
Citations by year: 2026: 318 · 2025: 343 · 2024: 295 · 2023: 330 · 2022: 284 · 2021: 306 · 2020: 275 · 2019: 230 · 2018: 217 · 2017: 219 · 2016: 198 · 2015: 189 · 2014: 176 · 2013: 162 · 2012: 141
FWCI: 13.46
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 5123 d)
Locations: Journal of Pain (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Institute of Neurological Disorders and Stroke (R01NS058870, R01NS038253, R01NS039518)
National Institute of Dental and Craniofacial Research (R01DE017821)
Topics: Health Sciences › Medicine › Physiology (medical) › Pain Mechanisms and Treatments
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Health Sciences › Medicine › Anesthesiology and Pain Medicine › Pain Management and Treatment
Keywords: central sensitization, hyperalgesia, synaptic plasticity, nociceptive pathways, glutamate receptors, metabotropic glutamate receptors, ionotropic glutamate receptors, inflammatory pain, neuropathic pain, chronic pain, membrane excitability
MeSH terms: Afferent Pathways, Animals, Central Nervous System, Humans, Hyperalgesia, Synaptic Transmission, Neuronal Plasticity, Nociceptors, Pain, Sensory Receptor Cells, Pain Threshold

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Central Sensitization: A Generator of Pain Hypersensitivity by Central Neural Plasticity

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