Pro-inflammatory alterations identified in people with non-specific low back pain

Non-specific low back pain is the term given to the presence of tension, pain or stiffness in the lower back region which is not attributable to any specific pathology and is not considered a symptom of another disease. Depending on its duration, low back pain may be classified as: acute (less than 6 weeks), subacute (between 6 and 12 weeks), or chronic (12 weeks or more) pain. According to the World Health Organisation, non-specific low back pain is one of the main causes of disability, with a lifetime prevalence of between 70% and 90%. Specifically, of the 291 health problems explored in the international Global Burden of Disease survey, low back pain leads the ranking in terms of years lived with disability.

Although the causes and mechanisms of non-specific low back pain remain obscure, previous investigations indicate an alteration of the cytokines involved in inflammatory processes and in the HPA axis associated with the stress-response system.

The research team, made up of the Psychological Research on Fibromyalgia and Chronic Pain Group (AGORA Group) of the Sant Joan de Déu Research Institute (IRSJD) - Sant Joan de Déu Health Park and the Universitat Autònoma de Barcelona (UAB), conducted an in-depth systematic review of the scientific literature published on non-specific low back pain, including for the first time pain-free participants as a control group.

As opposed to previous systematic reviews of non-specific low back pain, the review conducted by the research team used pain-free persons as a control group and had three differentiating purposes. Firstly, the review sought to describe the levels of pro-inflammatory cytokines which are altered in patients with non-specific low back pain. Secondly, it aimed to identify the compensatory anti-inflammatory response triggered by inflammation. And lastly, it attempted to define the HPA axis's dysregulation, which activates the cortisol response as a result of the stressful effects produced by continuous exposure to pain.

"Contrary to what had been believed up to now, this study shows that we can establish which immune-inflammatory and HPA-axis biomarkers are really altered in persons with non-specific low back pain, thanks to the use of healthy controls as a measure of comparison. This new neuroendocrine-immunological knowledge about non-specific low back pain will allow us to deal with new pharmacological and psychological treatment targets with the aim of following a more personalised and accurate therapeutic approach in the future," states Ariadna Colomer, member of the Psychological Research on Fibromyalgia and Chronic Pain Group (AGORA Group; IRSJD & UAB), who is carrying out her doctoral thesis on this subject.

Altered pro-inflammatory and HPA-axis biomarkers

"Our analyses provided preliminary evidence of a significant increase of pro-inflammatory biomarkers, including growth differentiation factor 15 (GDF-15), interleukin-23 (IL-23), transforming growth factor-beta (TGF-β), and soluble tumour necrosis factor receptor 1 (sTNF-R1), in patients with non-specific low back pain, compared to healthy controls. This fact leads one to think that the pro-inflammatory state may be involved in non-specific low back pain mechanisms, and we believe that these biomarkers could be considered therapeutic targets. Lastly, we also observed alterations in the response of cortisol, one of the biomarkers related to the HPA axis. Even so, further studies must be conducted with a large sample size if strong conclusions are to be drawn," in the words of Dr Juan Vicente Luciano, coordinator of the Psychological Research on Fibromyalgia and Chronic Pain Group (AGORA Group; IRSJD & UAB).

Contrary to what had been expected, as opposed to previous systematic reviews which did not use pain-free persons as a control group, the research team did not observe alterations in interleukin-6 (IL-6), the tumour necrosis factor alpha (TNF-α), or high sensitivity C-reactive protein (hs-CRP). Consequently, these three biomarkers should probably not be considered preferred therapeutic targets in persons with non-specific low back pain. Additionally, the team found incongruent evidence regarding anti-inflammatory cytokines, depending on the type of low back pain involved: acute, subacute or chronic.

"Bearing in mind the results presented here, we now know which pro-inflammatory biomarkers really are altered in non-specific low back pain processes. Likewise, we have learned that persons who suffer chronic low back pain (a type of non-specific low back pain) present low anti-inflammatory levels as a result of a long-time pro-inflammatory state."

The investigation was conducted by the Psychological Research on Fibromyalgia and Chronic Pain Group (AGORA Group), an inter-institutional research team (IRSJD & UAB) led by Dr Juan Vicente Luciano. The group worked in close cooperation with the Universitat de Barcelona (UB) and Chulalongkorn University (Bangkok, Thailand). The study has been published in the scientific journal Frontiers in Immunology.

Article: Sanabria-Mazo JP, Colomer-Carbonell A, Carmona-Cervelló M, Feliu-Soler A, Borràs X, Grasa M, Esteve M, Maes M, Edo S, Sanz A, Luciano JV. Immune-inflammatory and hypothalamic-pituitary-adrenal axis biomarkers are altered in patients with non-specific low back pain: A systematic review. Front Immunol. 2022 Sep 2;13:945513. doi: 10.3389/fimmu.2022.945513. PMID: 36119028; PMCID: PMC9478440.