Neuroimmune responses following joint mobilisation and manipulation in people with persistent neck pain: a protocol for a randomised placebo-controlled trial

Schipholt, Ivo J. Lutke; Scholten-Peeters, Gwendolyne G M; Bontkes, Hetty J.; Coppieters, Michel W.

doi:10.1136/bmjopen-2021-055748

Cited by 3 publications

(11 citation statements)

References 78 publications

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“…The flow diagram of the study is presented in Supplementary material C . The people with non-specific neck pain in the present study were also part of another study with identical selection criteria to investigate the effects of joint mobilization and manipulation on neuroimmune responses in non-specific neck pain ( Lutke Schipholt et al, 2022 ). For that study, 112 people with non-specific neck pain participated.…”

Section: Resultsmentioning

confidence: 99%

“…As summary measures, we calculated an inflammatory, pro-inflammatory, and anti-inflammatory index, for both in vitro and ex vivo levels, and the ratios between pro- and anti-inflammatory indices ( Lutke Schipholt et al, 2022 ). This reduced the number of main analyses substantially.…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…For exploration, individual inflammation markers were analyzed as secondary outcomes (Generaal et al, 2014). Inflammatory indices were calculated as the sum of all Ln-transformed (to create normal distributed data) z-standardized markers divided by the total number of markers used (Lutke Schipholt et al, 2022 The MHI-5 consist of five statements regarding psychological wellbeing. The final MHI-5 score is calculated by summing up the item scores and transforming this score to a scale varying from 0 to 100, with lower scores indicating more severe depressive symptoms (Cuijpers et al, 2009).…”

Section: Inflammatory Indicesmentioning

confidence: 99%

“…People with non-specific neck pain (n = 134), cervical radiculopathy (n = 36), and healthy participants (n = 26) were assessed for eligibility criteria, of whom 112 people with nonspecific neck pain, 25 with cervical radiculopathy and 23 healthy participants were included in the study. The flow diagram of the study is presented in Supplementary material C. The people with non-specific neck pain in the present study were also part of another study with identical selection criteria to investigate the effects of joint mobilization and manipulation on neuroimmune responses in non-specific neck pain (Lutke Schipholt et al, 2022). For that study, 112 people with nonspecific neck pain participated.…”

Section: Demographic and Clinical Variablesmentioning

confidence: 99%

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Systemic neuroimmune responses in people with non-specific neck pain and cervical radiculopathy, and associations with clinical, psychological, and lifestyle factors

Schipholt

Scholten-Peeters

Koop

et al. 2022

Front. Mol. Neurosci.

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Neuroimmune responses remain understudied in people with neck pain. This study aimed to (1) compare a broad range of systemic neuroimmune responses in people with non-specific neck pain (N = 112), cervical radiculopathy (N = 25), and healthy participants (N = 23); and (2) explore their associations with clinical, psychological and lifestyle factors. Quantification of systemic neuroimmune responses involved ex vivo serum and in vitro evoked-release levels of inflammatory markers, and characterization of white blood cell phenotypes. Inflammatory indices were calculated to obtain a measure of total immune status and were considered the main outcomes. Differences between groups were tested using analyses of covariance (ANCOVA) and multivariable regression models. Compared to healthy participants, the ex vivo pro-inflammatory index was increased in people with non-specific neck pain (β = 0.70, p = 0.004) and people with cervical radiculopathy (β = 0.64, p = 0.04). There was no difference between non-specific neck pain and cervical radiculopathy (β = 0.23, p = 0.36). Compared to non-specific neck pain, people with cervical radiculopathy showed lower numbers of monocytes (β = −59, p = 0.01). There were no differences between groups following in vitro whole blood stimulation (p ≥ 0.23) or other differences in the number and phenotype of white blood cells (p ≥ 0.07). The elevated ex vivo neuroimmune responses in people with non-specific neck pain and radiculopathy support the contention that these conditions encompass inflammatory components that can be measured systemically. There were multiple significant associations with clinical, psychological and lifestyle factors, such as pain intensity (β = 0.25) and anxiety (β = 0.23) in non-specific neck pain, visceral adipose tissue (β = 0.43) and magnification (β = 0.59) in cervical radiculopathy, and smoking (β = 0.59) and visceral adipose tissue (β = 0.52) in healthy participants. These associations were modified by sex, indicating different neuroimmune associations for females and males.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Inflammatory Indicesmentioning

confidence: 99%

Section: Demographic and Clinical Variablesmentioning

confidence: 99%

See 3 more Smart Citations

Systemic neuroimmune responses in people with non-specific neck pain and cervical radiculopathy, and associations with clinical, psychological, and lifestyle factors

Schipholt

Scholten-Peeters

Koop

et al. 2022

Front. Mol. Neurosci.

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Immediate systemic neuroimmune responses following spinal mobilisation and manipulation in people with non-specific neck pain: a randomised placebo-controlled trial

Schipholt

Coppieters

Reijm

et al. 2023

Sci Rep

Self Cite

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Spinal mobilisation/manipulation is a common intervention for spinal pain, yet the working mechanisms are largely unknown. A randomised placebo-controlled trial was conducted to (1) compare the immediate neuroimmune responses following spinal mobilisation/manipulation and placebo spinal mobilisation/manipulation; (2) compare the immediate neuroimmune responses of those with a good outcome with those of a poor outcome following spinal mobilisation/manipulation; and (3) explore the association between neuroimmune responses and pain reduction. One hundred patients were randomly allocated to spinal mobilisation/manipulation or a placebo mobilisation/manipulation. Primary outcomes were whole blood in-vitro evoked released concentrations of IL-1β and TNF-α measured 10 min and 2 h after the intervention. Immediate effects were studied because successful mobilisation/manipulation is often associated with immediate pain reduction, and immediate neuroimmune responses are less affected by potential confounders than long-term responses. Secondary outcomes included multiple systemic inflammatory marker concentrations, phenotypic analysis of white blood cells and clinical outcomes. Outcomes were compared between the experimental and placebo group, and between people with a good and poor outcome in the experimental group. Estimates of intervention effects were based on intention-to-treat analyses, by using linear mixed-effect models. Although there was a substantial difference in pain reduction between groups (mean (SD) difference visual analogue scale: 30 (21) mm at 10 min and 32 (21) mm at 2 h (p < 0.001) in favour of mobilisation/manipulation, there were no differences in primary outcomes between groups or between people with a good and poor outcome (p ≥ 0.10). In conclusion, possible neuroimmune responses following spinal mobilisations/manipulation cannot be identified at a systemic level. Future research may focus on longer treatment duration and more localised neuroimmune responses.

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Neuraxial biomechanics, fluid dynamics, and myodural regulation: rethinking management of hypermobility and CNS disorders

Frost,

Barclay

2024

Front. Neurol.

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Individuals with joint hypermobility and the Ehlers-Danlos Syndromes (EDS) are disproportionately affected by neuraxial dysfunction and Central Nervous System (CNS) disorders: such as Spontaneous Intracranial Hypotension (SIH) due to spinal cerebrospinal fluid (CSF) leaks, Upper Cervical Instability (UCI; including craniocervical or atlantoaxial instability (CCI/AAI)), Occult Tethered Cord Syndrome (TCS), Chiari Malformation (CM) and Idiopathic Intracranial Hypertension (IIH). The neuraxis comprises the parts of the nervous system (brain, nerves, spinal cord) along the craniospinal axis of the body. Neuraxial tissue includes all tissue structures that comprise, support, sheath, and connect along the neuraxis and peripheral nerves. Altered mechanical loading or vascular supply of neural structures can adversely impact neural health and conductivity, with local and remote effects on inflammation, venous congestion, and muscle control. With EDS characterized by altered structure of the connective tissues found throughout the body including the neural system, altered mechanical properties of the central nervous system (CNS) and its surrounding tissue structures are important considerations in the development and diagnostics of these CNS disorders, as well as response to therapeutic interventions. Experts have identified a need for neuraxial curriculum in medical education and hypermobility-adapted treatment approaches in pain management, neurosurgery, anesthesiology, hematology, gastrointestinal surgery, dermatology, cardiology, dentistry, gastroenterology, allergy/immunology, physical therapy, primary care, radiology and emergency medicine. This paper reviews the interactions between neuraxial biomechanics and pathology related to CNS disorders seen commonly with EDS. First, we provide a concise synthesis of the literature on neuraxial kinematics and fluid dynamics. We then discuss the interplay of these biomechanics and their involvement in clinically-relevant diagnoses and overlapping symptom presentations, modeling physiological reasoning to highlight knowledge gaps, support clinical decision-making, improve multidisciplinary management of hypermobility-associated complexity, and add weight to the call for medical education reform.

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Neuroimmune responses following joint mobilisation and manipulation in people with persistent neck pain: a protocol for a randomised placebo-controlled trial

Cited by 3 publications

References 78 publications

Systemic neuroimmune responses in people with non-specific neck pain and cervical radiculopathy, and associations with clinical, psychological, and lifestyle factors

Systemic neuroimmune responses in people with non-specific neck pain and cervical radiculopathy, and associations with clinical, psychological, and lifestyle factors

Immediate systemic neuroimmune responses following spinal mobilisation and manipulation in people with non-specific neck pain: a randomised placebo-controlled trial

Neuraxial biomechanics, fluid dynamics, and myodural regulation: rethinking management of hypermobility and CNS disorders

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