What determines a positive outcome of spinal manipulation for persistent low back pain: stiffness or pain sensitivity?

Low back pain (LBP) is the number one cause of years lived with disability, and it is the most common reason for primary care visits. However, we have limited knowledge regarding its mechanism, and we are currently limited to categorizing 90% of LBP patients as nonspecific. A standard treatment of non-specific LBP is spinal manipulative therapy (SMT), which aims to normalize specific spinal dysfunction. However, there is currently no available method of quantifying these spinal dysfunctions. This leaves clinicians using manual palpation to locate them and aim SMT at that vertebral target. Research indicates that locating a stiff or tender vertebra is used to determine the target.

Hence, quantifying stiffness has gained much traction using different mechanical indentation devices, and the preliminary results have been of interest. It appears that SMT does change stiffness but only for those who respond. Recently, a novel device, the VerteTrack (VT), has been developed. Through continuous rolling mechanical indentation of the lumbar spine, the VT allows us to record stiffness values at multiple vertebrae, non-invasively and rapidly, in a fashion that simulates manual palpation. Thus, the VT provides a new approach to quantifying stiffness. Tenderness and pain sensitivity are different aspects and is commonly measured in human subjects using quantitative sensory pain testing (QST). Much research has focused on changes in QST following SMT with conflicting results. However, it appears that regional mechanical pain sensitivity is affected by SMT.

We have little knowledge of how SMT works and whether further mechanistic knowledge can optimize the treatment. Finally, we do not know how joint stiffness and pain sensitivity interact together. Therefore, the objectives of this thesis were i) to elucidate the vertebral target site’s effect when applying SMT in persistent LBP patients. More specifically, we will examine if SMT targeting the stiffest or most pain-sensitive vertebra can differentiate the responses from patient-reported and experimental outcomes. We will also examine whether responding to the treatment impacts the experimental outcomes and whether a general hyperalgesic state predicts these changes. Finally, we will examine how vertebral stiffness and pain sensitivity are associated. ii) We will incorporate these results into a systematic review with comparative literature to examine whether applying SMT at a specific target improves patient-reported outcomes compared to a comparator target.

To answer objective I, we conducted a clinical trial that randomized 132 participants with non-specific LBP to receive four standardized SMT sessions directed at either the stiffest or most pain-sensitive vertebra. We used the VT to quantify stiffness and included an extensive QST battery a total of three times: at baseline, following the fourth and final treatment, and again after two weeks. A total of 123 completed the trial. Due to differences in vertebral markings at the different time points, we had to omit approximately 12% of the vertebral data (VT, pressure pain threshold (PPT), and heat pain threshold). However, we developed a mathematical method to avoid this potential limitation in future research by spatially synchronizing the lumbar trajectories/markings.

We examined changes in patient-reported LBP intensity, disability, and the experimental measures obtained at each time point compared to baseline using linear mixed methods. Afterward, we dichotomized the participants into responders/non-responders. We used latent class analysis to cluster the cohort using the baseline QST data into two groups: a sensitized and a non-sensitized group. We also examined how the different vertebral measures correlated with each other and how they differed between the individual vertebrae. Furthermore, we conducted a systematic review that examined four databases to answer objective ii. The literature was extracted independently by two investigators and scored for quality using Cochrane’s risk of bias tool. We provide a narrative report of the results.

We found that the participants improved regardless of the targeted vertebra or the different attempts to subgroup. While their improvement was statistically significant, we questioned whether this was of clinical relevance. The limited change was most likely due to the persistence of LBP in this sample. Nevertheless, the lack of an effect when targeting a specific vertebra is consistent with our systematic literature review, which included ten studies. In contrast to the preliminary results, we failed to find any changes in stiffness. However, we did find that PPT increased in three different settings: 

I The group where treatment was targeted at the most pain-sensitive vertebra, independent of responder status.
II The responders, independent of the targeted vertebra.
III The sensitive group, independent of the targeted vertebra.

Thus, SMT appears to mediate changes in PPT as a neurophysiological reflex, both nonspecific and specific, to the vertebra targeted, independent of clinical improvement, but also, due to overall clinical improvement. A caveat was that this was not a placebo-controlled trial. Hence, the causality of our findings is questionable. The remaining QSTs displayed limited modulations throughout, and none of them were of clinical relevance. Finally, we unexpectedly found that high degrees of stiffness correlate with high PPT scores (low pain sensitivity), thereby questioning if a stiff spine is an unfavorable attribute or if psychological factors impact this relationship. 

To conclude, based on the current results and the existing literature, there is no data to support the clinical relevance of being specific when targeting SMT. Future research that examines PPT changes following SMT should try to account for the three instances reported. Finally, future studies utilizing the VT as a repeated measure should ensure spatial synchronization before continuing with the data analysis.