Temporal development of peripheral neuroinflammation in whiplash-associated disorder grade II and its role in chronicity

Ridehalgh, Colette, Fundaun, Joel, Bremner, Stephen, Cercignani, Mara ORCID: https://orcid.org/0000-0002-4550-2456, Koushesh, Soraya, Schmid, Annina B. and Dilley, Andrew 2025. Temporal development of peripheral neuroinflammation in whiplash-associated disorder grade II and its role in chronicity. PAIN 10.1097/j.pain.0000000000003816

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Abstract

Whiplash injuries cause considerable pain and disability. Most individuals are diagnosed with whiplash-associated disorder grade II (WADII), which is defined by the absence of frank nerve injury. However, studies indicate possible peripheral neuroinflammation in some individuals with WADII that may contribute to symptoms. The temporal changes of peripheral neuroinflammation in WADII remain unclear. This study aimed to investigate the course of peripheral neuroinflammation from acute to chronic stages and assess whether neuroinflammation in the acute stage predicts recovery 6 months postinjury. Sixty-two WADII participants, who were examined within 4 weeks of a whiplash injury, returned for a follow-up appointment at 6 months. Thirty-two percent (n = 20) of participants considered themselves to be all better at 6 months based on a global recovery question. Magnetic resonance imaging T2-weighted signal ratio of the C5 to C8 roots of the brachial plexus, associated dorsal root ganglia, and median nerve, were similar at both time points. Signs of heightened nerve mechanosensitivity reduced significantly at 6 months, as did mechanical and thermal hyperalgesia in the upper limb. Inflammatory mediator serum levels were unaltered at 6 months, except for tumour necrosis factor-α, which was reduced. Multivariable regression analysis indicated that heightened nerve mechanosensitivity (reduced elbow range of motion) in the acute stage was weakly prognostic for neuropathic pain classification at 6 months. Although many participants recovered at 6 months, the data show that peripheral neuroinflammation may persist in some individuals. These findings highlight the complexity of WADII and the contribution of neuroinflammation in both acute and chronic stages.

Item Type:	Article
Date Type:	Published Online
Status:	In Press
Schools:	Schools > Psychology Research Institutes & Centres > Cardiff University Brain Research Imaging Centre (CUBRIC)
Publisher:	Lippincott, Williams & Wilkins
ISSN:	0304-3959
Date of First Compliant Deposit:	28 October 2025
Date of Acceptance:	28 July 2025
Last Modified:	28 Oct 2025 11:45
URI:	https://orca.cardiff.ac.uk/id/eprint/181946

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