Reduction of Chronic Primary Low Back Pain by Spinal Manipulative Therapy is Accompanied by Decreases in Segmental Mechanical Hyperalgesia and Pain Catastrophizing: A Randomized Placebo-controlled Dual-blind Mixed Experimental Trial.

Chronic primary low back pain (CPLBP) refers to low back pain that persists over 3 months, that cannot be explained by another chronic condition, and that is associated with emotional distress and disability. Previous studies have shown that spinal manipulative therapy (SMT) is effective in relieving CPLBP, but the underlying mechanisms remain elusive. This randomized placebo-controlled dual-blind mixed experimental trial (NCT05162924) aimed to investigate the efficacy of SMT to improve CPLBP and its underlying mechanisms. Ninety-eight individuals with CPLBP and 49 controls were recruited. Individuals with CPLBP received SMT (n = 49) or a control intervention (n = 49), 12 times over 4 weeks. The primary outcomes were CPLBP intensity (0-100 on a numerical rating scale) and disability (Oswestry Disability Index). Secondary outcomes included pressure pain thresholds in 4 body regions, pain catastrophizing, Central Sensitization Inventory, depressive symptoms, and anxiety scores. Individuals with CPLBP showed widespread mechanical hyperalgesia (P < .001) and higher scores for all questionnaires (P < .001). SMT reduced pain intensity compared with the control intervention (mean difference: -11.7 [95% confidence interval, -11.0 to -12.5], P = .01), but not disability (P = .5). Similar mild to moderate adverse events were reported in both groups. Mechanical hyperalgesia at the manipulated segment was reduced after SMT compared with the control intervention (P < .05). Pain catastrophizing was reduced after SMT compared with the control intervention (P < .05), but this effect was not significant after accounting for changes in clinical pain. Although the reduction of segmental mechanical hyperalgesia likely contributes to the clinical benefits of SMT, the role of pain catastrophizing remains to be clarified. PERSPECTIVE: This randomized controlled trial found that 12 sessions of SMT yield greater relief of CPLBP than a control intervention. These clinical effects were independent of expectations, and accompanied by an attenuation of hyperalgesia in the targeted segment and a modulation of pain catastrophizing.

Urinary TNF-α as a potential biomarker for chronic primary low back pain.

Introduction: Over two thirds of individuals with low back pain (LBP) may experience recurrent or persistent symptoms in the long term. Yet, current data do not allow to predict who will develop chronic low back pain and who will recover from an acute episode. Elevated serum levels of the proinflammatory cytokine tumor necrosis factor-α (TNF-α) have been associated with poor recovery and persistent pain following an acute episode of LBP. Inflammatory cytokines may also mediate mechanisms involved in nociplastic pain, and thus, have significant implications in chronic primary low back pain (CPLBP). Methods: This study aimed to investigate the potential of urinary TNF-α levels for predicting outcomes and characterizing clinical features of CPLBP patients. Twenty-four patients with CPLBP and 24 sex- and age-matched asymptomatic controls were recruited. Urinary TNF-α concentrations were measured at baseline and after 4 weeks, during which CPLBP patients underwent spinal manipulative therapy (SMT). Results: Concentrations of TNF-α were found to be elevated in baseline urine samples of CPLBP patients compared to asymptomatic controls. Moreover, these values differed among patients depending on their pain trajectory. Patients with persistent pain showed higher levels of TNF-α, when compared to those with episodic CPLBP. Furthermore, baseline TNF-α concentrations and their changes after 4 weeks predicted alterations in pain intensity and disability following SMT in patients with CPLBP. Discussion: These findings warrant further research on the potential use of urinary TNF-α concentrations as a prognostic biomarker for CPLBP.

A network analysis on biopsychosocial factors and pain-related outcomes assessed during a COVID-19 lockdown.

Psychological stress, social isolation, physical inactivity, and reduced access to care during lockdowns throughout a pandemic negatively impact pain and function. In the context of the first COVID-19 lockdown in Spain, we aimed to investigate how different biopsychosocial factors influence chiropractic patients' pain-related outcomes and vice-versa. A total of 648 chiropractic patients completed online questionnaires including variables from the following categories: demographics, pain outcomes, pain beliefs, impact of the COVID-19 pandemic, stress/anxiety and self-efficacy. Twenty-eight variables were considered in a cross-sectional network analysis to examine bidirectional associations between biopsychosocial factors and pain outcomes. Subgroup analyses were conducted to estimate differences according to gender and symptom duration. The greatest associations were observed between pain duration and pain evolution during lockdown. Participants' age, pain symptoms' evolution during lockdown, and generalized anxiety were the variables with the strongest influence over the whole network. Negative emotions evoked by the pandemic were indirectly associated with pain outcomes, possibly via pain catastrophizing. The network structure of patients reporting acute pain showed important differences when compared to patients with chronic pain. These findings will contribute to identify which factors explain the deleterious effects of both the pandemic and the restrictions on patients living with pain.

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.

Identification of Potential Visceral Pain Biomarkers in Colon Exudates from Mice with Experimental Colitis: An Exploratory In Vitro Study.

Chronic visceral pain (CVP) is extremely difficult to diagnose, and available analgesic treatment options are quite limited. Identifying the proteins secreted from the colonic nociceptors, or their neighbor cells within the tube walls, in the context of disorders that course with visceral pain, might be useful to decipher the mechanism involved in the establishment of CVP. Addressing this question in human with gastrointestinal disorders entails multiple difficulties, as there is not a clear classification of disease severity, and colonic secretion is not easy to manage. We propose using of a murine model of colitis to identify new algesic molecules and pathways that could be explored as pain biomarkers or analgesia targets. Descending colons from naïve and colitis mice with visceral hyperalgesia were excised and maintained ex vivo. The proteins secreted in the perfusion fluid before and during acute noxious distension were evaluated using high-resolution mass spectrometry (MS). Haptoglobin (Hp), PZD and LIM domain protein 3 (Pdlim3), NADP-dependent malic enzyme (Me1), and Apolipoprotein A-I (Apoa1) were increased during visceral insult, whilst Triosephosphate isomerase (Tpi1), Glucose-6-phosphate isomerase (Gpi1), Alpha-enolase (Eno1), and Isoform 2 of Tropomyosin alpha-1 chain (Tpm1) were decreased. Most identified proteins have been described in the context of different chronic pain conditions and, according to gene ontology analysis, they are also involved in diverse biological processes of relevance. Thus, animal models that mimic human conditions in combination with unbiased omics approaches will ultimately help to identify new pathophysiological mechanisms underlying pain that might be useful in diagnosing and treating pain. PERSPECTIVE: Our study utilizes an unbiased proteomic approach to determine, first, the clinical relevance of a murine model of colitis and, second, to identify novel molecules/pathways involved in nociception that would be potential biomarkers or targets for chronic visceral pain.

From hands-on to remote: Moderators of response to a novel self-management telehealth programme during the COVID-19 pandemic.

BACKGROUND: In March 2020, state-wide lockdowns were declared in many countries, including Spain. Citizens were confined to their homes and remotely supported activities were prioritized as an alternative to in-person interactions. Previous data suggest that remote and self-management interventions may be successful at reducing pain and related psychological variables. However, individual factors influencing the effectiveness of these interventions remain to be identified. We aimed to investigate the psychological and motivational factors moderating changes in pain observed in chiropractic patients undertaking a novel telehealth self-management programme. METHODS: A cohort of 208 patients from a chiropractic teaching clinic was recruited to participate in the study. Patients received telehealth consultations and individualized self-management strategies tailored for their current complaint. They were encouraged to make use of these strategies daily for 2-4 weeks, whilst rating their pain intensity, motivation and adherence. Validated questionnaires were completed online to assess catastrophizing, kinesiophobia and anxiety. RESULTS: A total of 168 patients completed the first 2 weeks of the programme, experiencing significant reductions in all variables. Kinesiophobia emerged as a key factor influencing pain reduction and moderating the association between motivation and pain relief. In turn, adherence to the programme was associated with lower pain intensity, although moderated by the degree of motivation. CONCLUSIONS: In the context of COVID-19, when introducing remote and self-management strategies, pain cognitions and motivational factors should be taken into consideration to foster adherence and yield better pain outcomes.

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.

Pain catastrophizing mediates rapid benefits of accessing in-person chiropractic care during the COVID-19 lockdown.

BACKGROUND: In March 2020, the COVID-19 pandemic forced the Spanish government to declare a state of emergency. A stringent lockdown was enforced, restricting access to healthcare services, including chiropractic. Reduced access to care provision in combination with psychological stress, social isolation and physical inactivity during the lockdown were shown to negatively influence pain conditions. However, data on strategies to mitigate the impact of the pandemic on these conditions are lacking. METHODS: Upon easing of restrictions in May 2020, 51 chiropractic clinics throughout Spain pseudo-randomly invited patients, recruiting a total of 385 participants. During a 14-day period, participants were exposed to in-person chiropractic care in either one (n = 177) or multiple encounters (n = 109) or to no care (n = 99). The effects of access to chiropractic care on patients' pain-related and psychological outcomes were assessed online through validated self-reported questionnaires before and after the period of care. Coprimary outcomes included pain intensity, pain interference and pain cognitions. RESULTS: When comparing to participants without access to care, pain intensity and interference were significantly decreased at follow-up, irrespective of the number of encounters. Kinesiophobia was also significantly reduced at follow-up, though only after multiple encounters. The relationship between fear of movement, changes in pain intensity and interference was mediated by catastrophizing. CONCLUSION: Access to in-person chiropractic care may provide pain relief, associated with reductions in interference and pain cognitions. Prioritizing in-person care for patients with maladaptive pain cognitions may help dampen the detrimental consequences of the pandemic on physical and psychological well-being.

Neurophysiological mechanisms of chiropractic spinal manipulation for spine pain.

Together, neck pain and back pain are the first cause of disability worldwide, accounting for more than 10% of the total years lived with disability. In this context, chiropractic care provides a safe and effective option for the management of a large proportion of these patients. Chiropractic is a healthcare profession mainly focused on the spine and the treatment of spinal disorders, including spine pain. Basic studies have examined the influence of chiropractic spinal manipulation (SM) on a variety of peripheral, spinal and supraspinal mechanisms involved in spine pain. While spinal cord mechanisms of pain inhibition contribute at least partly to the pain-relieving effects of chiropractic treatments, the evidence is weaker regarding peripheral and supraspinal mechanisms, which are important components of acute and chronic pain. This narrative review highlights the most relevant mechanisms of pain relief by SM and provides a perspective for future research on SM and spine pain, including the validation of placebo interventions that control for placebo effects and other non-specific effects that may be induced by SM. SIGNIFICANCE: Spinal manipulation inhibits back and neck pain partly through spinal segmental mechanisms and potentially through peripheral mechanisms regulating inflammatory responses. Other mechanisms remain to be clarified. Controls and placebo interventions need to be improved in order to clarify the contribution of specific and non-specific effects to pain relief by spinal manipulative therapy.

Combined Chiropractic and Podiatric Treatment for Chronic Low Back Pain Concomitant With a Unilateral Pronated Foot: Protocol for a Multicenter Pilot Randomized Controlled Trial.

Objective: The purpose of this article is to describe a protocol to examine the feasibility of combining podiatric orthotic treatment with multimodal chiropractic treatment to treat chronic low back pain (CLBP) in those with a functional short leg on the same side as a unilateral pronated foot. Methods: This is a protocol for a multicenter feasibility 2-arm parallel randomized controlled trial. One hundred and thirty-two adults with CLBP and a functional short leg on the same side as a unilateral pronated foot are to be recruited in Melbourne, Australia, and Madrid and Seville, Spain. Forty-four participants at each site are to be randomized to multimodal chiropractic treatment including spinal manipulation or to multimodal chiropractic treatment also involving spinal manipulation, together with podiatric custom-made orthoses. Chiropractic visits are to comprise 12 treatments over 4 weeks. Outcome measures will be recruitment, compliance, costs, CLBP-related disability, and perceived low back pain. Results: Feasibility results will be reported in text format and the clinical data reported using descriptive statistics focusing on any clinically significant results. Conclusion: This protocol describes a feasibility study for assessing the combination of podiatric orthotic treatment with multimodal chiropractic treatment to treat CLBP in those with a functional short leg on the same side as a unilateral pronated foot.

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.

Characterisation of the correlation between standing lordosis and degenerative joint disease in the lower lumbar spine in women and men: a radiographic study.

BACKGROUND: Degenerative joint disease (DJD) in the lumbar spine is a common condition that is associated with chronic low back pain. Excessive loading of lumbar joints is a risk factor for DJD. Changes in lumbar lordosis significantly redistribute the forces of weight-bearing on the facet joints and the intervertebral discs. However, the relationship between lumbar lordosis and DJD has not been characterized in men and women. METHODS: We characterised the correlation between standing lumbar lordosis and DJD in standing radiographic images from 301 adult female and male chiropractic patients. DJD was rated using the Kellgren-Lawrence scale, and lordosis was measured using the Cobb angle. Linear and curvilinear correlations were investigated while controlling for age and sex. RESULTS: We found a highly significant curvilinear correlation between lordosis and DJD of the lower lumbar spine in both sexes, but especially in women, irrespective of the effects of age. We found the effect size of lordosis on lower lumbar DJD to be between 17.4 and 18.1% in women and 12.9% in older men. In addition, lordosis of 65 (95% CI 55.3-77.7) and 68 (98% CI 58.7-73.3) degrees were associated with minimal DJD in the lower lumbar spine of women and men respectively, and were therefore considered 'optimal'. This optimal lordotic angle was 73 (95% CI 58.8-87.2) degrees in older men. CONCLUSIONS: Both hypo- and hyper-lordosis correlate with DJD in the lumbar spine, particularly in women and in older men. These findings may well be of relevance to spinal pain management and spinal rehabilitation.