Browse by Audience
Multiple Sclerosis (MS) is a debilitating autoimmune disease often accompanied by severe chronic pain. The most common type of pain in MS, called neuropathic pain, arises from disease processes affecting the peripheral and central nervous systems. It is incredibly difficult to study these processes in patients, so animal models such as experimental autoimmune encephalomyelitis (EAE) mice are used to dissect the complex mechanisms of neuropathic pain in MS. The pleiotropic cytokine tumor necrosis factor α (TNFα) is a critical factor mediating neuropathic pain identified by these animal studies. The TNF signaling pathway is complex, and can lead to cell death, inflammation, or survival. In complex diseases such as MS, signaling through the TNFR1 receptor tends to be pro-inflammation and death, whereas signaling through the TNFR2 receptor is pro-homeostatic. However, most TNFα-targeted therapies indiscriminately block both arms of the pathway, and thus are not therapeutic in MS. This review explores pain in MS, inflammatory TNF signaling, the link between the two, and how it could be exploited to develop more effective TNFα-targeting pain therapies.
Learn More >Chronic pain, a severe public health issue, affects the quality of life of patients and results in a major socioeconomic burden. Only limited drug treatments for chronic pain are available, and they have insufficient efficacy. Recent studies have found that the expression of long non-coding RNAs (lncRNAs) is dysregulated in various chronic pain models, including chronic neuropathic pain, chronic inflammatory pain, and chronic cancer-related pain. Studies have also explored the effect of these dysregulated lncRNAs on the activation of microRNAs, inflammatory cytokines, and so on. These mechanisms have been widely demonstrated to play a critical role in the development of chronic pain. The findings of these studies indicate the significant roles of dysregulated lncRNAs in chronic pain in the dorsal root ganglion and spinal cord, following peripheral or central nerve lesions. This review summarizes the mechanism underlying the abnormal expression of lncRNAs in the development of chronic pain induced by peripheral nerve injury, diabetic neuropathy, inflammatory response, trigeminal neuralgia, spinal cord injury, cancer metastasis, and other conditions. Understanding the effect of lncRNAs may provide a novel insight that targeting lncRNAs could be a potential candidate for therapeutic intervention in chronic pain.
Learn More >Previous studies have shown an increase of insulin-like growth factor-2 (IGF2) in animal models of neuropathic pain. We aimed to examine the hypothesis that reducing the expression of IGF2 using intrathecal IGF2 small-interfering RNA (siRNA) would attenuate the development of neuropathic pain in rats after spared nerve injury (SNI). Male Wistar rats were divided into three groups: sham-operated group, in which surgery was performed to cut the muscles without injuring the nerves; SNI group, in which SNI surgery was performed to sever the nerves; and SNI + siRNA IGF2 group, in which SNI surgery was performed, and IGF2-siRNA was administered intrathecally 1 day after SNI. The rats were assessed for mechanical allodynia and cold allodynia 1 day before surgery (baseline), and at 2, 4, 6, 8, and 10 days after siRNA treatment. The rat spinal cord was collected for quantitative polymerase chain reaction and western blot analysis. Compared with the SNI group, rats that received IGF2 siRNA showed a significantly increased SNI-induced paw-withdrawal threshold to metal filament stimulation from Day 4 to Day 10 after SNI surgery. IGF2 siRNA significantly decreased the response duration from the acetone test from Day 2 to Day 10 following SNI surgery. SNI increased IGF2 mRNA expression on Day 2 and increased IGF2 protein expression on Day 8 and Day 10 in the spinal cord of the SNI rats. However, the above-mentioned effects of IGF2 mRNA and protein expression were significantly inhibited in the SNI + IGF2 siRNA group. We demonstrated that intrathecal administration of IGF2 siRNA provided significant inhibition of SNI-induced neuropathic pain via inhibition of IGF2 expression in the spinal cord. The analgesic effect lasted for 10 days. Further exploration of intrathecal IGF2 siRNA administration as a potential therapeutic strategy for neuropathic pain is warranted.
Learn More >: The COVID-19 pandemic presents one of the greatest threats to pediatric pain care seen in generations. Due to public health restrictions, many pediatric pain clinics halted in-person appointments, delaying and disrupting access to care. There is no existing research on the impacts of COVID-19 on pediatric chronic pain care in Canada or the challenges experienced by health care professionals and pain clinics. : The aim of this study was to evaluate the impact of COVID-19 on Canadian pediatric chronic pain care by documenting how health care professionals provided care during the first six months of the pandemic. : Two Canadian online cross-sectional surveys were conducted: one among Canadian pediatric pain clinic directors (Study 1) and another among multidisciplinary pediatric pain health care professionals (Study 2). : Responses from 13/13 Canadian pediatric pain clinics/rehabilitation programs indicated that all clinics provided virtual care during the pandemic. No significant changes were reported on the frequency of appointment requests. Most clinics reported no perceived change in patient pain levels ( = 9/13, 69%) or occurrence of pain flares ( = 10/13, 77%). Results from 151 individual health care professionals indicated that the majority (90%) of non-emergency department respondents were providing virtual care. The main challenges of virtual care included technological barriers, financial concerns, infrastructure and logistics, privacy, and clinical challenges. : This study documented the impact of the COVID-19 pandemic on pediatric chronic pain care in Canada and highlighted the rapid shift to using virtual solutions. Simultaneously, respondents outlined current challenges and potential solutions to consider in the development of virtual care guidelines and policy in Canada.
Learn More >Data defining and subsequently guiding the use of psychotropic medications in children and adolescents is sparse. We conducted a meta-analysis of randomized control trials to examine the effectiveness of psychotropic medications in children and adolescents with chronic pain.
Learn More >Migraine is a symptomatically heterogeneous condition, of which headache is just one manifestation. Migraine is a disorder of altered sensory thresholding, with hypersensitivity among sufferers to sensory input. Advances in functional neuroimaging have highlighted that several brain areas are involved even prior to pain onset. Clinically, patients can experience symptoms hours to days prior to migraine pain, which can warn of impending headache. These symptoms can include mood and cognitive change, fatigue, and neck discomfort. Some epidemiological studies have suggested that migraine is associated in a bidirectional fashion with other disorders, such as mood disorders and chronic fatigue, as well as with other pain conditions such as fibromyalgia. This review will focus on the literature surrounding alterations in fatigue, mood, and cognition in particular, in association with migraine, and the suggested links to disorders such as chronic fatigue syndrome and depression. We hypothesize that migraine should be considered a neural disorder of brain function, in which alterations in aminergic networks integrating the limbic system with the sensory and homeostatic systems occur early and persist after headache resolution and perhaps interictally. The associations with some of these other disorders may allude to the inherent sensory sensitivity of the migraine brain and shared neurobiology and neurotransmitter systems rather than true co-morbidity.
Learn More >Risk assessment tools can improve clinical decision-making for individuals with musculoskeletal pain, but do not currently exist for predicting reduction of pain intensity as an outcome from physical therapy.
Learn More >Individuals with chronic pain often experience co-existing sleep problems and depression-related states. Chronic pain, sleep problems, and depression interrelate, and have been shown to exacerbate one another, which negatively impacts quality of life. This study explored the relationships between pain severity, pain interference, sleep quality, and depression among individuals with chronic pain. Secondly, we tested whether sleep quality may moderate the relationship between pain and depression. A cross-sectional survey was completed by 1,059 adults with non-malignant chronic pain conditions ( 43 years, 88% identified as women) and collected measures related to pain severity, pain interference, sleep quality, and depression. Multiple regression analyses found that pain severity, pain interference, and sleep quality are all significantly associated with depression. Secondly, moderated regression analyses revealed that sleep quality moderates the relationship between pain interference and depression among individuals with chronic pain such that good sleep quality attenuates the effect of pain interference on depression, and poor sleep quality amplifies the effect of pain interference on depression. These findings suggest that sleep quality may be a relevant therapeutic target for individuals with chronic pain and co-existing depression.
Learn More >Bidirectional interactions between the immune system and the nervous system are increasingly appreciated as playing a pathogenic role in chronic pain. Unraveling the mechanisms by which inflammatory pain is mediated through communication between nerves and immune cells may lead to exciting new strategies for therapeutic intervention. In this narrative review, we focus on the role of macrophages in the pathogenesis of osteoarthritis (OA) pain. From regulating homeostasis to conducting phagocytosis, and from inducing inflammation to resolving it, macrophages are plastic cells that are highly adaptable to their environment. They rely on communicating with the environment through cytokines, growth factors, neuropeptides, and other signals to respond to inflammation or injury. The contribution of macrophages to OA joint damage has garnered much attention in recent years. Here, we discuss how macrophages may participate in the initiation and maintenance of pain in OA. We aim to summarize what is currently known about macrophages in OA pain and identify important gaps in the field to fuel future investigations.
Learn More >Bortezomib is a pivotal drug for the management of multiple myeloma. However, bortezomib is a neurotoxic anticancer drug responsible for chemotherapy-induced peripheral neuropathy (CIPN). CIPN is associated with psychological distress and a decrease of health-related quality of life (HRQoL), but little is known regarding bortezomib-related CIPN. This single center, cross-sectional study assessed the prevalence and severity of sensory/motor CIPN, neuropathic pain and ongoing pain medications, anxiety, depression, and HRQoL, in multiple myeloma patients after the end of bortezomib treatment. Paper questionnaires were sent to patients to record the scores of sensory and motor CIPNs (QLQ-CIPN20), neuropathic pain (visual analogue scale and DN4 interview), anxiety and depression (HADS), the scores of HRQoL (QLQ-C30 and QLQ-MY20) and ongoing pain medications. Oncological data were recorded using chemotherapy prescription software and patient medical records. The prevalence of sensory CIPN was 26.9% (95% CI 16.7; 39.1) among the 67 patients analyzed and for a mean time of 2.9 ± 2.8 years since the last bortezomib administration. The proportion of sensory CIPN was higher among patients treated by intravenous and subcutaneous routes than intravenous or subcutaneous routes ( = 0.003). QLQ-CIPN20 motor scores were higher for patients with a sensory CIPN than those without ( < 0.001) and were correlated with the duration of treatment and the cumulative dose of bortezomib (coefficient: 0.31 and 0.24, = 0.01 and 0.0475, respectively), but not sensory scores. Neuropathic pain was screened in 44.4% of patients with sensory CIPN and 66.7% of them had ongoing pain medications, but none were treated with duloxetine (recommended drug). Multivariable analysis revealed that thalidomide treatment (odds-ratio: 6.7, 95% CI 1.3; 35.5, = 0.03) and both routes of bortezomib administration (odds-ratio: 13.4, 95% CI 1.3; 139.1, = 0.03) were associated with sensory CIPN. Sensory and motor CIPNs were associated with anxiety, depression, and deterioration of HRQoL. Sensory CIPN was identified in a quarter of patients after bortezomib treatment and associated with psychological distress that was far from being treated optimally. There is a need to improve the management of patients with CIPN, which may include better training of oncologists regarding its diagnosis and pharmacological treatment.
Learn More >