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Objective: The purpose of this study was to assess the effects of different spinal manipulation (SM) techniques and target segments on a specific dermatome and myotome, when compared with a remote spinal cord segment that served as a control location., Methods: Twenty-nine healthy volunteers were randomized to receive instrumental (Activator IV, Activator Methods International Ltd) or manual SM at the C6, C1, and T4 vertebral segments in 3 independent sessions. Pressure pain thresholds (PPTs) and muscle strength were examined at the C6 (test) and L4 (control) dermatomes and myotomes, at baseline and after intervention. Linear mixed-effects models were used to analyze changes over time and interindividual variability., Results: Pressure pain thresholds significantly increased at both proximal and distal C6 dermatome locations (P < .05), irrespective of the technique and segment of application (P > .2). No significant changes were observed at the L4 dermatome. Muscle strength remained unchanged throughout the study. Multilevel modeling revealed significant associations between increased PPTs along the C6 dermatome (P < .001), whereas the combination of technique and target segment predicted PPT increases at the proximal C6 dermatome., Conclusion: These findings support regional, rather than segmental mechanisms underlying the sensory effects of SM. Specifically, significant increases in PPTs along the C6 dermatome suggest localized effects on pain sensitivity, which may depend on the target spinal region. Further investigation is needed to better understand these regional changes of SM and their potential clinical implications., (Copyright © 2024. Published by Elsevier Inc.)

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., (Copyright © 2024 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Gevers-Montoro, Puente-Tobares, Monréal, Conesa-Buendía, Piché and Ortega-De Mues.)

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., (© 2023. The Author(s).)

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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., (© 2022 The Authors. European Journal of Pain published by John Wiley & Sons Ltd on behalf of European Pain Federation - EFIC®.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Gevers-Montoro, Romero-Santiago, Losapio, Conesa-Buendía, Newell, Álvarez-Galovich, Piché and Ortega-De Mues.)

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., (© 2021 European Pain Federation - EFIC®.)

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., (© 2022 by National University of Health Sciences.)

The COVID-19 pandemic has been associated with increased uncertainty, fear and worry in everyone's life. The effect of changes in daily life has been studied widely, but we do not know how emotion-regulation strategies influence adaptation to a new situation to help them overcome worry in the face of uncertainty. Here, 1,064 self-selected Farsi speaking participants completed an online battery of questionnaires that measured fear of virus and illness, worry, intolerance of uncertainty, and emotion regulation (two subscales: reappraisal, suppression). We also documented the number of daily COVID-19 cases and deaths due to COVID-19 on the day in which participants completed the questionnaire. Our findings suggest a correlation between contamination fear and the number of daily-confirmed cases (r = 0.11), and the number of reported deaths due to COVID-19 (r = 0.09). Worry mediated the relationship between intolerance of uncertainty and fear of virus and illness (b = 0.16, 0.1141 < CI < 0.2113). In addition, suppression moderated the relationship between intolerance of uncertainty and worry ( p < 0.01). Our results suggest that suppression (at least in the short term) can be an adaptive response to the worry associated with uncertainty. Suppression can reduce worry, which in turn can decrease fear of contamination and improve adaptation to social distancing requirements. Although, the observed correlations were significant, but considering the sample size, they are not strong, and they should be interpreted cautiously., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Khatibi, Sharpe, Dehghani, Ghalibaf, Hosseinchi, Mazidi, Ranjbar, Deldar, Gevers-Montoro, Alizadeh, Alidoust, Babaei, Telkabadi and Ghadiri.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Gevers-Montoro, Provencher, Descarreaux, Ortega de Mues and Piché.)

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., (© 2021 European Pain Federation - EFIC®.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Gevers-Montoro, Provencher, Northon, Stedile-Lovatel, Ortega de Mues and Piché.)

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.

Language processing involves other cognitive domains, including Working Memory (WM). Much detail about the neural correlates of language and WM interaction remains unclear. This review summarizes the evidence for the interaction between WM and language obtained via functional Magnetic Resonance Imaging (fMRI) in the past two decades. The search was limited to PubMed, Google Scholar, Science direct and Neurosynth for working memory, language, fMRI, neuroimaging, cognition, attention, network, connectome keywords. The exclusion criteria consisted of studies including children, older adults, bilingual or multilingual population, clinical cases, music, sign language, speech, motor processing, review papers, meta-analyses, electroencephalography/event-related potential, and positron emission tomography. A total of 20 articles were included and discussed in four categories: language comprehension, language production, syntax, and networks. Studies on neural correlates of WM and language interaction are rare. Language tasks that involve WM activate common neural systems. Activated areas can be associated with cognitive concepts proposed by Baddeley and Hitch (1974), including the phonological loop of WM (mainly Broca and Wernicke's areas), other prefrontal cortex and right hemispheric regions linked to the visuospatial sketchpad. There is a clear, dynamic interaction between language and WM, reflected in the involvement of subcortical structures, particularly the basal ganglia (caudate), and of widespread right hemispheric regions. WM involvement is levered by cognitive demand in response to task complexity. High WM capacity readers draw upon buffer memory systems in midline cortical areas to decrease the WM demands for efficiency. Different dynamic networks are involved in WM and language interaction in response to the task in hand for an ultimate brain function efficiency, modulated by language modality and attention., Competing Interests: Conflicts of interest: The authors declare no competing interests and no relationship that may lead to any conflict of interest., (© 2021 the Author(s), licensee AIMS Press.)