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

Abstract

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.

Exploring immune status in peripheral blood and tumor tissue in association with survival in patients with multi-organ metastatic colorectal cancer

“…Samples were collected in EDTA tubes and analyzed as previously described. 33 Samples were shipped to central laboratory at Cancer Center Amsterdam, Amsterdam UMC and processed within 48 hours. T cell subset analysis was performed on pre-washed whole blood, to prevent sequestering of CD25 antibody by plasma CD25, gated on the PBMC population by CD45 expression and sidward scatter as shown in Figure S1.…”

Integrating jigsaw puzzle thinking into practice: the assessment of cervical spine radiculopathy

“…There are key roles for inflammatory and immune processes in radiculopathy [20,26,27]. Although the literature separates inflammatory and immune processes, several core elements, macrophages, cytokines, chemokines, etc., are considered essential components of both.…”

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

“…Systemic inflammatory markers, such as high sensitive c-reactive protein (hsCRP) and tumor necrosis factor (TNF)-α may be elevated in people with persistent neck pain 7 and radicular pain 8 . These immune responses may be associated with pain intensity and perceived recovery, suggesting that spinal pain encompasses inflammatory components 7 , 9 . As systemic inflammation is upregulated and associated with clinical outcomes in people with non-specific neck pain, further interventional research is warranted to provide insights whether and how systemic inflammation can be reduced 9 .…”

“…These immune responses may be associated with pain intensity and perceived recovery, suggesting that spinal pain encompasses inflammatory components 7 , 9 . As systemic inflammation is upregulated and associated with clinical outcomes in people with non-specific neck pain, further interventional research is warranted to provide insights whether and how systemic inflammation can be reduced 9 . It has been proposed that spinal mobilisation/manipulation stimulates the hypothalamic–pituitary–adrenal-axis and the sympathetic-adrenal-medullary-axis, and subsequently promotes autonomic nervous system and immune system interactions diminishing systemic inflammation 10 , 11 .…”