• Graeme A Brazenor, Gregory M Malham, and Peter J Teddy.
• Department of Neurosurgery, Epworth Hospital, Richmond, Victoria, Australia.
• Pain Med. 2022 Jul 1; 23 (7): 1283-1298.

ObjectiveTo conduct a comprehensive search for evidence with regard to whether central sensitization after an injury can act as a persistent autonomous pain generator after the inducing injury has healed.MethodsWe searched Medline on PubMed and the Cochrane Library, screening 3,572 abstracts, from which 937 full-text articles were obtained, with 186 of these discarded as irrelevant to the question being posed. The remaining 751 articles were studied for evidence.ResultsFourteen publications were judged to provide weak evidence for the hypothesis of central sensitization as a persisting autonomous pain generator, but none addressed the question directly. No strong evidence for the affirmative answer was found. Sixty-one publications were judged to provide weak evidence for a negative answer, and ten were judged to provide strong evidence. Unexpectedly, serious weaknesses were discovered in the literature underpinning the validity of the clinical diagnosis of central sensitization in humans: 1) inappropriate extrapolation, in many publications, of laboratory animal data to humans; 2) failure to demonstrate the absence of peripheral pain generators that might be perpetuating central sensitization; and 3) many factors now shown to confound what is being measured by quantitative sensory testing, conditioned pain modulation, and the Central Sensitization Inventory.ConclusionsWe found no evidence proving that central sensitization can persist as an autonomous pain generator after the initiating injury has healed. Our review has also shown that the evidential basis for the diagnosis of central sensitization in individual patients is seriously in question.© The Author(s) 2021. Published by Oxford University Press on behalf of the American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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