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Recent observational studies have reported a negative association between physical activity and chronic back pain (CBP), but the causality of the association remains unknown. We introduce bidirectional Mendelian randomization (MR) to assess potential causal inference between physical activity and CBP. This two-sample MR used independent genetic variants associated with physical activity and CBP as genetic instruments from large genome-wide association studies (GWASs). The effects of both directions (physical activity to CBP and CBP to physical activity) were examined. Inverse variance-weighted meta-analysis and alternate methods (weighted median and MR-Egger) were used to combine the MR estimates of the genetic instruments. Multiple sensitivity analyses were conducted to examine the robustness of the results. The MR set parallel GWAS cohorts, among which, those involved in the primary analysis were comprised of 337,234 participants for physical activity and 158,025 participants (29,531 cases) for CBP. No evidence of a causal relationship was found in the direction of physical activity to CBP [odds ratio (OR), 0.98; 95% CI, 0.85-1.13; = 0.81]. In contrast, a negative causal relationship in the direction of CBP to physical activity was detected ( = -0.07; 95% CI, -0.12 to -0.01; = 0.02), implying a reduction in moderate-vigorous physical activity (approximately 146 MET-minutes/week) for participants with CBP relative to controls. The negative relationship between physical activity and CBP is probably derived from the reduced physical activity of patients experiencing CBP rather than the protective effect of physical activity on CBP.
Learn More >As the principal reason for low back pain, intervertebral disc degeneration (IDD) affects the health of people around the world regardless of race or region. Degenerative discs display a series of characteristic pathological changes, including cell apoptosis, senescence, remodeling of extracellular matrix, oxidative stress and inflammatory local microenvironment. As a serine/threonine-protein kinase in eukaryocytes, AMP-activated protein kinase (AMPK) is involved in various cellular processes through the modulation of cell metabolism and energy balance. Recent studies have shown the abnormal activity of AMPK in degenerative disc cells. Besides, AMPK regulates multiple crucial biological behaviors in IDD. In this review, we summarize the pathophysiologic changes of IDD and activation process of AMPK. We also attempt to generalize the role of AMPK in the pathogenesis of IDD. Moreover, therapies targeting AMPK in alleviating IDD are analyzed, for better insight into the potential of AMPK as a therapeutic target.
Learn More >Complex regional pain syndrome (CRPS) is a chronic pain disorder characterized by spontaneous or evoked regionally-confined pain which is out of proportion to the initial trauma event. The disease can seriously affect the quality of the patients' life, increase the psychological burden, and cause various degrees of disability. Despite the awareness of CRPS among medical practitioners for over a century, its pathogenesis remains unclear, and the available treatment is still unsatisfactory. Effective animal models are the foundation of disease research, which is helpful in understanding the pathogenesis and an in-depth exploration of the appropriate therapeutic approaches. Currently, researchers have established a series of animal models of the disease. There are four main CRPSI animal models: chronic post-ischemic pain (CPIP) model, tibial fracture/cast immobilization model, passive transfer-trauma model, and the needlestick-nerve-injury (NNI) model. The modeling methods of these models are constantly improving over time. In preclinical studies, the interpretation of experimental results and the horizontal comparison between similar studies may be affected by the nature of the experimental animal breeds, sex, diet, and psychology. There is need to facilitate the choice of appropriate animal models and avoid the interference of the factors influencing animal models on the interpretation of research results. The review will provide a basic overview of the influencing factors, modeling methods, and the characteristics of CRPSI animal models.
Learn More >Chronic Pain is among the leading causes of disability worldwide with up to 60% of patients suffering from comorbid depression. Psychedelic-assisted therapy has recently been found effective in treating a host of mental health issues including depression and has historically been found to be useful in treating pain. Reports of self-medication for chronic pain using psychedelic drugs have been widely documented, with anecdotal evidence indicating widespread success in a range of pathologies. In preparation for an upcoming trial, to better understand how those with lived experience of chronic pain self-medicate with psychedelic drugs, and to establish, in detail, their therapeutic protocols and practices for success. As part of patient-involvement (PI) for an upcoming trial in this population, 11 individuals who reported self-medicating with psychedelic drugs took part in a 1-h semi-structured discussion, which was then transcribed and thematically analyzed. Across a range of psychedelic substances and doses, reported pain scores improved substantially during and after psychedelic experiences. Two processes, Positive Reframing and Somatic Presence, were reliably identified as playing a role in improvements in mental wellbeing, relationship with pain, and physical (dis)comfort. Inclusion of other strategies such as mindfulness, breathwork, and movement were also widely reported. Due to the data's subjective nature, this paper is vulnerable to bias and makes no claims on causality or generalisability. Together, these results have been used to inform study design for a forthcoming trial. This pre-trial PI work gives us confidence to test psychedelic therapy for chronic pain in a forthcoming controlled trial. The results presented here will be instrumental in improving our ability to meet the needs of future study participants.
Learn More >Parental Catastrophizing and Goal Pursuit in the Context of Child Chronic Pain: A Daily Diary Study.
Despite daily variability in children's chronic pain experiences, little is known about how parents' emotions and goals toward their child's pain are influenced by these daily changes. This diary study examined how daily child pain intensity (as perceived by parents) moderates the associations between parental catastrophic thoughts about child pain on the one hand, and daily parental distress and parents' goals with regard to their child's pain (pain control vs. activity engagement) on the other hand. Participants were 25 parents of 20 different children = 18; 90% girls). Children, aged 8-14 years ( = 9.5, = 2.09), experienced either chronic headache or functional abdominal pain with an average pain duration of 22.5 months ( = 24.5 months). Daily parental responses (i.e., perceived child pain intensity, distress and goal endorsement) were collected through a 3-week daily diary (resulting in 413 valid diary reports). Parents completed the Pain Catastrophizing Scale for Parents prior to starting the diary (PCS-P general) and a daily measure (PCS-P daily) included in the diary. To account for the interdependence of the data, the data were analyzed using multilevel modeling. Perceived daily child pain intensity moderated the impact of parental general and daily catastrophic thoughts on parents' daily distress. Only for parents experiencing low general catastrophic thoughts an increase in distress was observed on days when they perceived their child's pain intensity as high. For all parents, high levels of perceived child pain intensity were related to more distress on days where parents reported high levels of catastrophic thinking (i.e., PCS-P daily). Perceived daily child pain intensity also moderated the impact of parental general catastrophic thinking on parents' daily endorsement of goals. Parents with high levels of general catastrophic thinking reported a lower focus on child pain control on days when child pain intensity was perceived to be low. Parents with low general catastrophic thinking reported lower endorsement of the activity engagement goal on days where the child's pain intensity was perceived to be low. These findings highlight the complexity of daily fluctuations in parental distress and goals regarding their child's pain. Clinical implications and future directions are critically assessed.
Learn More >Indigenous peoples are vulnerable populations that live in remote areas of the Amazon forest with limited access to health-care services. Underreporting and undertreatment of pain is a common event in the general population but little is known about these issues in indigenous peoples. The aim of this study was to investigate the characteristics and cultural aspects of pain management in five ethnicities of the Brazilian Amazon.
Learn More >Chronic low back pain or chronic cervical pain often has a neuropathic pain (NeP) component and patients with these conditions complain of sleep deprivation, loss of physical function, and reduced productivity due to pain. The objective of this study was to clarify the pathway by which pain, sleep disturbance due to pain, and physical function status influence QOL measures in chronic low back pain patients with NeP associated with lumbar spine diseases (CLBP-NeP) and in chronic cervical pain patients with NeP associated with cervical spine diseases (CCP-NeP).
Learn More >Chronic pain has been widely recognized as a major public health problem that impacts multiple aspects of patient quality of life. Unfortunately, chronic pain is often resistant to conventional analgesics, which are further limited by their various side effects. New therapeutic strategies and targets are needed to better serve the millions of people suffering from this devastating disease. To this end, recent clinical and preclinical studies have implicated the epidermal growth factor receptor signaling pathway in chronic pain states. EGFR is one of four members of the ErbB family of receptor tyrosine kinases that have key roles in development and the progression of many cancers. EGFR functions by activating many intracellular signaling pathways following binding of various ligands to the receptor. Several of these signaling pathways, such as phosphatidylinositol 3-kinase, are known mediators of pain. EGFR inhibitors are known for their use as cancer therapeutics but given recent evidence in pilot clinical and preclinical investigations, may have clinical use for treating chronic pain. Here, we review the clinical and preclinical evidence implicating EGFR in pathological pain states and provide an overview of EGFR signaling highlighting how EGFR and its ligands drive pain hypersensitivity and interact with important pain pathways such as the opioid system.
Learn More >Increasingly, studies have documented the negative impact of pain catastrophizing on health outcomes. The Pain Catastrophizing Scale (PCS) has been the measure of choice for many of these studies. The PCS provides 3 subscales for measuring pain catastrophizing: rumination, magnification, and helplessness. Factor analytic investigations of these factors have been limited by the sample size and relevance, and results have been inconsistent. No study has directly estimated the added value of subscale scoring of the PCS compared with scoring it as a single measure.
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