microRNA let-7i-5p mediates the relationship between muscle fat infiltration and neck pain disability following motor vehicle collision: a preliminary study.

Persistent neck-pain disability (PNPD) is common following traumatic stress exposures such as motor vehicle collision (MVC). Substantial literature indicates that fat infiltration into neck muscle (MFI) is associated with post-MVC PNPD. However, little is known about the molecular mediators underlying this association. In the current study, we assessed whether microRNA expression signatures predict PNPD and whether microRNA mediate the relationship between neck MFI and PNPD. A nested cohort of 43 individuals from a longitudinal study of MVC survivors, who provided blood (PAXgene RNA) and underwent magnetic resonance imaging (MRI), were included in the current study. Peritraumatic microRNA expression levels were quantified via small RNA sequencing, neck MFI via MRI, and PNPD via the Neck Disability Index two-weeks, three-months, and twelve-months following MVC. Repeated measures regression models were used to assess the relationship between microRNA and PNPD and to perform mediation analyses. Seventeen microRNA predicted PNPD following MVC. One microRNA, let-7i-5p, mediated the relationship between neck MFI and PNPD. Peritraumatic blood-based microRNA expression levels predict PNPD following MVC and let-7i-5p might contribute to the underlying effects of neck MFI on persistent disability. In conclusion, additional studies are needed to validate this finding.

Can cortisol levels predict the severity of acute whiplash-associated disorders?

BACKGROUND: The exact underlying mechanism of whiplash-associated disorders still remains obscure. Central sensitization of the brain to painful stimulus and disturbances in the hypothalamic-pituitary-adrenal axis has been suggested to contribute to the development of whiplash-associated disorders. Although cortisol is a well-known factor in the acute stress response and its effects on chronic pain sensation were studied, information is lacking regarding the relation between acute phase cortisol concentrations and the intensity of whiplash-associated disorders. The aim of this prospective observational study was to investigate the relationship between acute serum cortisol concentrations and the severity of whiplash-associated disorders. METHODS: 55 patients enrolled in the study and they answered a pertinent questionnaire. A blood sample was drawn to determine serum cortisol concentration. RESULTS: The mean cortisol concentration of the whiplash-associated disorder score 2-3 patients was significantly lower compared to the whiplash-associated disorder score 1 patients, 9.5 ± 6.9 vs. 13.22 ± 8.3 µg% (p = 0.02). The mean cortisol concentrations increased significantly from mild through moderate to serious grade of severity of accident as perceived by the patient, 9.64 ± 4.82, 11.59 ± 6.85, 17.39 ± 12.1 µg% (p = 0.02). CONCLUSIONS: The study supports the possibility that cortisol plays a role in the development of whiplash-associated disorders. Low or relatively low cortisol concentrations might be associated with more severe forms of the disorder.

Pathophysiology behind prolonged whiplash associated disorders: study protocol for an experimental study.

BACKGROUND: There is insufficient knowledge of pathophysiological parameters to understand the mechanism behind prolonged whiplash associated disorders (WAD), and it is not known whether or not changes can be restored by rehabilitation. The aims of the projects are to investigate imaging and molecular biomarkers, cervical kinaesthesia, postural sway and the association with pain, disability and other outcomes in individuals with longstanding WAD, before and after a neck-specific exercise intervention. Another aim is to compare individuals with WAD with healthy controls. METHODS: Participants are a sub-group (n = 30) of individuals recruited from an ongoing randomized controlled study (RCT). Measurements in this experimental prospective study will be carried out at baseline (before intervention) and at a three month follow-up (end of physiotherapy intervention), and will include muscle structure and inflammation using magnetic resonance imaging (MRI), brain structure and function related to pain using functional MRI (fMRI), muscle function using ultrasonography, biomarkers using samples of blood and saliva, cervical kinaesthesia using the "butterfly test" and static balance test using an iPhone app. Association with other measures (self-reported and clinical measures) obtained in the RCT (e.g. background data, pain, disability, satisfaction with care, work ability, quality of life) may be investigated. Healthy volunteers matched for age and gender will be recruited as controls (n = 30). DISCUSSION: The study results may contribute to the development of improved diagnostics and improved rehabilitation methods for WAD. TRIAL REGISTRATION: Clinicaltrial.gov Protocol ID: NCT03664934, initial release 09/11/2018.

The course of serum inflammatory biomarkers following whiplash injury and their relationship to sensory and muscle measures: a longitudinal cohort study.

Tissue damage or pathological alterations are not detectable in the majority of people with whiplash associated disorders (WAD). Widespread hyperalgisa, morphological muscle changes and psychological distress are common features of WAD. However little is known about the presence of inflammation and its association with symptom persistence or the clinical presentation of WAD. This study aimed to prospectively investigate changes in serum inflammatory biomarker levels from the acute (<3 weeks) to chronic (>3 months) stages of whiplash injury. It also aimed to determine relationships between biomarker levels and hyperalgesia, fatty muscle infiltrates of the cervical extensors identified on MRI and psychological factors. 40 volunteers with acute WAD and 18 healthy controls participated. Participants with WAD were classified at 3 months as recovered/mild disability or having moderate/severe disability using the Neck Disability Index. At baseline both WAD groups showed elevated serum levels of CRP but by 3 months levels remained elevated only in the moderate/severe group. The recovered/mild disability WAD group had higher levels of TNF-α at both time points than both the moderate/severe WAD group and healthy controls. There were no differences found in serum IL-1ß. Moderate relationships were found between hyperalgesia and CRP at both time points and between hyperalgesia and IL-1ß 3 months post injury. There was a moderate negative correlation between TNF-α and amount of fatty muscle infiltrate and pain intensity at 3 months. Only a weak relationship was found between CRP and pain catastrophising and no relationship between biomarker levels and posttraumatic stress symptoms. The results of the study indicate that inflammatory biomarkers may play a role in outcomes following whiplash injury as well as being associated with hyperalgesia and fatty muscle infiltrate in the cervical extensors.

Reduction in high blood tumor necrosis factor-alpha levels after manipulative therapy in 2 cervicogenic headache patients.

OBJECTIVE: This case report discusses the treatment of 2 patients with cervicogenic headache (CHA) attending the Outpatient Clinic of the Hungarian National Institute for Rheumatology and Physiotherapy (Budapest, Hungary) and reviews the pathophysiology, therapeutic strategy, and problems associated with the treatment of CHA. CLINICAL FEATURES: Patient 1 was a 27-year-old female who sustained a whiplash injury. A sharp, shooting headache developed, readily induced, and aggravated by just bending the neck backward or by turning her head. Magnetic resonance imaging revealed a disk protrusion at C4-C5 pressing the anterior cerebrospinal space. Patient 2 was a 62-year-old female who sustained a whiplash injury; her cervical movements became restricted, which precipitated headaches. Magnetic resonance imaging revealed a paramedian disk hernia between the C4 and C5 vertebrae that intruded into the right ventral cerebrospinal space. INTERVENTION AND OUTCOME: After 4 weeks of manipulative therapy for patient 1, both active and passive range of motion returned to normal, and the high tumor necrosis factor-alpha (TNF-alpha) level (63 pg/mL) was substantially reduced (28 pg/mL). Patient 2 was started on manipulative therapy twice a week for 4 weeks; after 2 months, the patient became symptom-free, and high TNF-alpha level (72 pg/mL) was reduced greatly (35 pg/mL). CONCLUSION: Two patients with whiplash injury and disk herniation developed CHA associated with very high TNF-alpha levels. After manipulative therapy, these patients became symptom-free, and their TNF-alpha levels decreased substantially.

Whiplash: a biochemical study of muscle injury.

Outcome following whiplash injury of the cervical spine is variable, and the pathology of those with prolonged symptoms is uncertain. We undertook a prospective study in 25 patients to identify whether those with prolonged symptoms following whiplash injury exhibit a rise in serum creatine kinase consistent with significant muscle damage at the time of injury. Transient rise in creatine kinase level was seen in only 2 of 25 patients, neither of whom complained of prolonged symptoms. Of the 8 patients who developed chronic symptoms following whiplash injury, none demonstrated a serum creatine kinase rise. Prolonged symptoms following whiplash injury cannot be explained by biochemically measurable muscle damage.