Antibiotics a cure for back pain, a false dawn or a new era?

Abstract

The recent publication in this journal of papers by Albert and colleagues [1,2] from Denmark suggesting that low grade anaerobic bacterial infection may be the underlying cause of significant persistent chronic back pain in a welldefined group of patients has precipitated an unprecedented response in the medical and lay media. In the midst of claim and counterclaim, these studies represent a significant and substantial change in our understanding of the pathophysiology of back pain in some patient groups, and the importance of this should not be lost amidst the negative, unstructured and unscientific response to this study. The factsThe story starts in 2001 with the publication of a research letter in the Lancet by a group from Birmingham [3] demonstrating that 31 % of patients with sciatica tested positive to a newly developed serological test, which diagnosed deep-seated infections caused by virulent Grampositive microorganisms. In addition, intervertebral disc material excised during microdiscectomy in a different group of patients, which was cultured in a specialist anaerobic environment, had positive cultures after longterm incubation in 53 % of patients and of this group 84 % grew Propionibacterium acnes.Following the ISSLS 2006 meeting, a collaboration developed between the Birmingham group and the group from Southern Denmark. This led to publication of a pilot study in 2008 [4] where 32 chronic low back pain patients with Modic type 1 endplate changes and a previous lumbar herniated disc were treated with amoxicillin and clavulanate for 90 days. In this uncontrolled trial, there was a clinically important and statistically significant difference in outcome at 10-month follow-up following antibiotic treatment.In the meantime, the evidence was accumulating about the significant correlation between Modic endplate changes and back pain. Albert and Manniche [5] identified a strong association between Modic changes and non-specific low back pain, a stronger association with Modic type 1 than type 2, and that a lumbar disc herniation is a strong risk factor for developing Modic changes, especially type 1, during the following year and that these changes are strongly associated with low back pain.A systematic review from Southern Denmark in 2008 [6] identified the prevalence of vertebral endplate signal changes as 43 % in patients with non-specific low back pain and/or sciatica, and 6 % in a non-clinical population, demonstrating that endplate changes are associated with pain. A further systematic review in the same year from Shanghai [7] identified two possible pathophysiological mechanisms for Modic changes-one biomechanical and one biochemical. A biomechanical pathway for development of Modic changes was supported by a large population MRI scan study in 2011 [8].Against this background two key papers were then published in this journal in 2013. In one study [2] Albert and colleagues established a strong relationship between

Modic (endplate) changes in the lumbar spine: bone micro-architecture and remodelling

“…A recent study has suggested antibiotic treatment as an effective option for a specific subgroup of patients with Modic type 1 changes [9]. Significant controversy has followed, with a number of authors raising concerns about the methodology and conclusion of that study [41][42][43][44][45][46][47][48][49][50][51][52]. Within the restrictions of our specimen size, and our study being a bone micro-architecture and remodelling study, not aimed at investigating bacterial infection, our histological slides of the bone biopsies (H&E stained) did not show associated oedema and no cellular infiltrate to indicate overt inflammation.…”

“…However, the material analysed in the present study included bone biopsies only, and not intervertebral disc which may contain bacteria and show inflammation. This remains a controversial topic, in need of further research as suggested by numerous letters to this journal [41][42][43][44][45][46][47][48][49][50][51][52]. Hence, evidence supporting the biomechanical and biochemical hypotheses is still not sufficient, and it remains unclear how they may play a synergistic role in the development of Modic changes in the human body [3].…”

Modic Changes and Disc Degeneration Caused by Inoculation ofPropionibacterium acnesinside Intervertebral Discs of Rabbits: A Pilot Study

“…Nevertheless, there has been controversies and argumentation against the relationship between bacteria and Modic changes, highlighting that the isolated P. acnes was the contamination during tissue harvest rather than the original colonization inside intervertebral discs [ 12 ]. In addition, the lack of deterministic causal evidence based on animal studies was another major defect [ 13 ]. To solve this problem, Koch's Postulates, which demonstrate that pathogenic microbes isolated from patients could cause the same disease in animal models, were a reasonable method [ 14 , 15 ].…”

The Michel Benoist and Robert Mulholland Yearly European Spine Journal Review: a survey of the “surgical and research” articles in the European Spine Journal, 2013

“…The authors conclude that in this very specific group of chronic low back pain, antibiotic treatment is effective. As one might expect this startling development (reminiscent of the discovery that peptic ulcer was due to helicobacter infection has led to considerable discussion [14][15][16] and even two editorials [8]). The paper by O'Dowd and Casey [16] deserves careful reading, emphasising not only the important significance of these papers, but also the fact that these are a small group of patients, not representative of a large population of patients with chronic low back pain.…”