Mechanisms of chiropractic spinal manipulative therapy for patients with chronic primary low back pain: Protocol for a mechanistic randomised placebo-controlled trial

Introduction Chronic low back pain (CLBP) is a highly prevalent and disabling condition. Identifying subgroups of patients afflicted with CLBP is a current research priority, for which a classification system based on pain mechanisms was proposed. Spinal manipulative therapy (SMT) is recommended for the management of CLBP. Yet, little data are available regarding its mechanisms of action, making it difficult to match this intervention to the patients who may benefit the most. It was suggested that SMT may influence mechanisms associated with central sensitisation. Therefore, classifying patients with CLBP according to central sensitisation mechanisms may help predict their response to SMT. Methods and analysis This protocol describes a randomised placebo-controlled trial aiming to examine which variables linked to central sensitisation may help predict the clinical response to SMT in a cohort of patients with CLBP. One hundred patients with chronic primary low back pain will be randomised to receive 12 sessions of SMT or placebo SMT over a 4-week period. Pain intensity and disability will be assessed as primary outcomes after completing the 4-week treatment (primary endpoint), and at 4-week and 12-week follow-ups. Baseline values of two pain questionnaires, lumbar pressure pain thresholds, concentrations of an inflammatory cytokine and expectations of pain relief will be entered as predictors of the response to SMT in a multiple regression model. Changes in these variables after treatment will be used in a second multiple regression model. The reference values of these predictors will be measured from 50 age and sex-matched healthy controls to allow interpretation of values in patients. Mixed analyses of variance will also be conducted to compare the primary outcomes and the predictors between groups (SMT vs placebo) over time (baseline vs post-treatment). Ethics and dissemination Ethical approval was granted by the Fundación Jiménez Díaz Clinical Research Ethics Committee. Trial registration number NCT05162924

Effects of chiropractic spinal manipulation on laser-evoked pain and brain activity

The aim of this study was to examine the mechanisms underlying hypoalgesia induced by spinal manipulation (SM). Eighty-two healthy volunteers were assigned to one of the four intervention groups: no intervention, SM at T4 (homosegmental to pain), SM at T8 (heterosegmental to pain) or light mechanical stimulus at T4 (placebo). Eighty laser stimuli were applied on back skin at T4 to evoke pain and brain activity related to Aδ- and C-fibers activation. The intervention was performed after 40 stimuli. Laser pain was decreased by SM at T4 (p = 0.028) but not T8 (p = 0.13), compared with placebo. However, brain activity related to Aδ-fibers activation was not significantly modulated (all p > 0.05), while C-fiber activity could not be measured reliably. This indicates that SM produces segmental hypoalgesia through inhibition of nociceptive processes that are independent of Aδ fibers. It remains to be clarified whether the effect is mediated by the inhibition of C-fiber activity. [Figure not available: see fulltext.]. © 2021, The Author(s)

Clinical effectiveness and efficacy of chiropractic spinal manipulation for spine pain

Spine pain is a highly prevalent condition affecting over 11% of the world's population. It is the single leading cause of activity limitation and ranks fourth in years lost to disability globally, representing a significant personal, social, and economic burden. For the vast majority of patients with back and neck pain, a specific pathology cannot be identified as the cause for their pain, which is then labeled as non-specific. In a growing proportion of these cases, pain persists beyond 3 months and is referred to as chronic primary back or neck pain. To decrease the global burden of spine pain, current data suggest that a conservative approach may be preferable. One of the conservative management options available is spinal manipulative therapy (SMT), the main intervention used by chiropractors and other manual therapists. The aim of this narrative review is to highlight the most relevant and up-to-date evidence on the effectiveness (as it compares to other interventions in more pragmatic settings) and efficacy (as it compares to inactive controls under highly controlled conditions) of SMT for the management of neck pain and low back pain. Additionally, a perspective on the current recommendations on SMT for spine pain and the needs for future research will be provided. In summary, SMT may be as effective as other recommended therapies for the management of non-specific and chronic primary spine pain, including standard medical care or physical therapy. Currently, SMT is recommended in combination with exercise for neck pain as part of a multimodal approach. It may also be recommended as a frontline intervention for low back pain. Despite some remaining discrepancies, current clinical practice guidelines almost universally recommend the use of SMT for spine pain. Due to the low quality of evidence, the efficacy of SMT compared with a placebo or no treatment remains uncertain. Therefore, future research is needed to clarify the specific effects of SMT to further validate this intervention. In addition, factors that predict these effects remain to be determined to target patients who are more likely to obtain positive outcomes from SMT

Chiropractic spinal manipulation prevents secondary hyperalgesia induced by topical capsaicin in healthy individuals

Background and Aims: Spinal manipulation (SM) is currently recommended for the management of back pain. Experimental studies indicate that the hypoalgesic mechanisms of SM may rely on inhibition of segmental processes related to temporal summation of pain and, possibly, on central sensitization, although this remains unclear. The aim of this study was to determine whether experimental back pain, secondary hyperalgesia, and pain-related brain activity induced by capsaicin are decreased by segmental SM. Methods: Seventy-three healthy volunteers were randomly allocated to one of four experimental groups: SM at T5 vertebral level (segmental), SM at T9 vertebral level (heterosegmental), placebo intervention at T5 vertebral level, or no intervention. Topical capsaicin was applied to the area of T5 vertebra for 40 min. After 20 min, the interventions were administered. Pressure pain thresholds (PPTs) were assessed outside the area of capsaicin application at 0 and 40 min to examine secondary hyperalgesia. Capsaicin pain intensity and unpleasantness were reported every 4 min. Frontal high-gamma oscillations were also measured with electroencephalography. Results: Pain ratings and brain activity were not significantly different between groups over time (p > 0.5). However, PPTs were significantly decreased in the placebo and control groups (p < 0.01), indicative of secondary hyperalgesia, while no hyperalgesia was observed for groups receiving SM (p = 1.0). This effect was independent of expectations and greater than placebo for segmental (p < 0.01) but not heterosegmental SM (p = 1.0). Conclusions: These results indicate that segmental SM can prevent secondary hyperalgesia, independently of expectations. This has implications for the management of back pain, particularly when central sensitization is involved

Presence of tumor necrosis factor-alpha in urine samples of patients with chronic low back pain undergoing chiropractic care: Preliminary findings from a prospective cohort study

Background and aims: Low back pain is the leading cause of years lived with disability worldwide. Chiropractors employ different interventions to treat low back pain, including spinal manipulative therapy, although the mechanisms through which chiropractic care improves low back pain are still unclear. Clinical research and animal models suggest that spinal manipulation might modulate plasma levels of inflammatory cytokines, which have been involved in different stages of low back pain. More specifically, serum levels of Tumor Necrosis Factor-alpha (TNF-α) have been found to be elevated in patients with chronic low back pain. We aimed to investigate whether urine from chronic low back pain patients could be an appropriate medium to measure concentrations of TNF-α and to examine possible changes in its levels associated to chiropractic care. Methods: Urine samples were collected from 24 patients with chronic low back pain and TNF-α levels were analyzed by ELISA before and after 4–6 weeks of care compared to a reference value obtained from 5 healthy control subjects, by means of a Welch’s t-test. Simultaneously, pain intensity and disability were also evaluated before and after care. Paired t-tests were used to compare mean pre and post urinary concentrations of TNF-α and clinical outcomes. Results: Significantly higher baseline levels of urinary TNF-α were observed in chronic low back pain patients when compared to our reference value (p < 0.001), which were significantly lower after the period of chiropractic treatment (p = 0.03). Moreover, these changes were accompanied by a significant reduction in pain and disability (both p < 0.001). However, levels of urinary TNF-α were not correlated with pain intensity nor disability. Conclusion: These results suggest that urine could be a good milieu to assess TNF-α changes, with potential clinical implications for the management of chronic low back pain. Copyright © 2022 Gevers-Montoro, Romero-Santiago, Losapio, Conesa-Buendía, Newell, Álvarez-Galovich, Piché and Ortega-De Mues