Does peripheral neuroinflammation predict chronicity following whiplash injury? Protocol for a prospective cohort study
Introduction Whiplash-associated disorder grade 2 (WAD2) is characterised by musculoskeletal pain/tenderness but no apparent nerve injury. However, studies have found clinical features indicative of neuropathy and neuropathic pain. These studies may indicate peripheral nerve inflammation, since prec...
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BMJ Publishing Group
2022-12-01
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| Series: | BMJ Open |
| Online Access: | https://bmjopen.bmj.com/content/12/12/e066021.full |
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| author | Mara Cercignani Stephen Bremner Alex Novak Chetan Trivedy Colette Ridehalgh Joel Fundaun Rupert Young Jane Greening Annina Schmid Andrew Dilley |
| author_facet | Mara Cercignani Stephen Bremner Alex Novak Chetan Trivedy Colette Ridehalgh Joel Fundaun Rupert Young Jane Greening Annina Schmid Andrew Dilley |
| author_sort | Mara Cercignani |
| collection | DOAJ |
| description | Introduction Whiplash-associated disorder grade 2 (WAD2) is characterised by musculoskeletal pain/tenderness but no apparent nerve injury. However, studies have found clinical features indicative of neuropathy and neuropathic pain. These studies may indicate peripheral nerve inflammation, since preclinical neuritis models found mechanical sensitivity in inflamed, intact nociceptors. The primary aim of this study is to establish the contribution of peripheral neuroinflammation to WAD2 and its role in prognosis. Participants will be invited to participate in a sub-study investigating the contribution of cutaneous small fibre pathology to WAD2.Methods and analysis 115 participants within 1 month following whiplash injury and 34 healthy control participants will be recruited and complete validated questionnaires for pain, function and psychological factors. Data collection will take place at the Universities of Sussex and Oxford, UK. Clinical examination, quantitative sensory testing and blood samples will be undertaken. MRI scans using T2-weighted and diffusion tensor images of the brachial plexus and wrist will determine nerve inflammation and nerve structural changes. Skin biopsies from a substudy will determine structural integrity of dermal and intraepidermal nerve fibres. At 6 months, we will evaluate recovery using Neck Disability Index and a self-rated global recovery question and repeat the outcome measures. Regression analysis will identify differences in MRI parameters, clinical tests and skin biopsies between participants with WAD2 and age/gender-matched controls. Linear and logistic regression analyses will assess if nerve inflammation (MRI parameters) predicts poor outcome. Mixed effects modelling will compare MRI and clinical measures between recovered and non-recovered participants over time.Ethics and dissemination Ethical approval was received from London-Brighton and Sussex Research Ethics Committee (20/PR/0625) and South Central—Oxford C Ethics Committee (18/SC/0263). Written informed consent will be obtained from participants prior to participation in the study. Results will be disseminated through publications in peer-reviewed journals, presentations at national/international conferences and social media.Trial registration number NCT04940923. |
| format | Article |
| id | doaj-art-e922ce9cc5d24cf1996d19116601cf6d |
| institution | OA Journals |
| issn | 2044-6055 |
| language | English |
| publishDate | 2022-12-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | BMJ Open |
| spelling | doaj-art-e922ce9cc5d24cf1996d19116601cf6d2025-08-20T02:28:20ZengBMJ Publishing GroupBMJ Open2044-60552022-12-01121210.1136/bmjopen-2022-066021Does peripheral neuroinflammation predict chronicity following whiplash injury? Protocol for a prospective cohort studyMara Cercignani0Stephen Bremner1Alex Novak2Chetan Trivedy3Colette Ridehalgh4Joel Fundaun5Rupert Young6Jane Greening7Annina Schmid8Andrew Dilley95 Neuroimaging Laboratory, Santa Lucia Foundation, Rome, ItalyClinical Trials Unit, Brighton and Sussex Medical School, Brighton, Brighton and Hove, UK2 Emergency Medicine Research Oxford (EMROx), John Radcliffe Hospital, Oxford, UKEmergency Departments, University Hospitals Sussex NHS Foundation Trust, Brighton, UKDepartment of Neuroscience, Brighton and Sussex Medical School, Brighton, UKNuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UKSchool of engineering and informatics, University of Sussex, Brighton, UKDepartment of Neuroscience, Brighton and Sussex Medical School, Brighton, UK3 Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UKDepartment of Neuroscience, Brighton and Sussex Medical School, Brighton, UKIntroduction Whiplash-associated disorder grade 2 (WAD2) is characterised by musculoskeletal pain/tenderness but no apparent nerve injury. However, studies have found clinical features indicative of neuropathy and neuropathic pain. These studies may indicate peripheral nerve inflammation, since preclinical neuritis models found mechanical sensitivity in inflamed, intact nociceptors. The primary aim of this study is to establish the contribution of peripheral neuroinflammation to WAD2 and its role in prognosis. Participants will be invited to participate in a sub-study investigating the contribution of cutaneous small fibre pathology to WAD2.Methods and analysis 115 participants within 1 month following whiplash injury and 34 healthy control participants will be recruited and complete validated questionnaires for pain, function and psychological factors. Data collection will take place at the Universities of Sussex and Oxford, UK. Clinical examination, quantitative sensory testing and blood samples will be undertaken. MRI scans using T2-weighted and diffusion tensor images of the brachial plexus and wrist will determine nerve inflammation and nerve structural changes. Skin biopsies from a substudy will determine structural integrity of dermal and intraepidermal nerve fibres. At 6 months, we will evaluate recovery using Neck Disability Index and a self-rated global recovery question and repeat the outcome measures. Regression analysis will identify differences in MRI parameters, clinical tests and skin biopsies between participants with WAD2 and age/gender-matched controls. Linear and logistic regression analyses will assess if nerve inflammation (MRI parameters) predicts poor outcome. Mixed effects modelling will compare MRI and clinical measures between recovered and non-recovered participants over time.Ethics and dissemination Ethical approval was received from London-Brighton and Sussex Research Ethics Committee (20/PR/0625) and South Central—Oxford C Ethics Committee (18/SC/0263). Written informed consent will be obtained from participants prior to participation in the study. Results will be disseminated through publications in peer-reviewed journals, presentations at national/international conferences and social media.Trial registration number NCT04940923.https://bmjopen.bmj.com/content/12/12/e066021.full |
| spellingShingle | Mara Cercignani Stephen Bremner Alex Novak Chetan Trivedy Colette Ridehalgh Joel Fundaun Rupert Young Jane Greening Annina Schmid Andrew Dilley Does peripheral neuroinflammation predict chronicity following whiplash injury? Protocol for a prospective cohort study BMJ Open |
| title | Does peripheral neuroinflammation predict chronicity following whiplash injury? Protocol for a prospective cohort study |
| title_full | Does peripheral neuroinflammation predict chronicity following whiplash injury? Protocol for a prospective cohort study |
| title_fullStr | Does peripheral neuroinflammation predict chronicity following whiplash injury? Protocol for a prospective cohort study |
| title_full_unstemmed | Does peripheral neuroinflammation predict chronicity following whiplash injury? Protocol for a prospective cohort study |
| title_short | Does peripheral neuroinflammation predict chronicity following whiplash injury? Protocol for a prospective cohort study |
| title_sort | does peripheral neuroinflammation predict chronicity following whiplash injury protocol for a prospective cohort study |
| url | https://bmjopen.bmj.com/content/12/12/e066021.full |
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