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There is currently a knowledge gap regarding persistent opioid use after hip fracture surgery. Thus, opioid use within a year after hip fracture surgery in patients with/without opioid use before surgery was examined.
Learn More >Among youth with chroic pain, elevated somatic symptoms across multiple body systems have been associated with greater emotional distress and functional disability and could represent poor adaptation to pain. The Children's Somatic Symptoms Inventory (formerly the Children's Somatization Inventory) is commonly used to assess somatic symptoms in children. However, no studies have evaluated the clinical utility of the measure in the assessment of pediatric patients with chronic pain. This study evaluated the factor structure and clinical relevance of the 24-item Children's Somatic Symptoms Inventory (CSSI-24) in youth (n = 1150) with mixed chronic pain complaints presenting to a tertiary pain clinic. CSSI-24 total scores were equal or superior to factor scores as indicators of patients' clinical characteristics (functional disability, pain catastrophizing, fear of pain, anxiety and depressive symptoms) and parental catastrophizing and protective responses. Tertile-derived clinical reference points for the CSSI-24 total score (<18: low, 19 – 31: moderate, ≥ 32: high) significantly differed on measures of clinical characteristics and parent factors. Controlling for age, sex, pain intensity and primary pain complaint, the high somatic symptoms group exhibited significantly greater health care utilization compared to the moderate and low groups. Assessment of somatic symptoms in pediatric patients with chronic pain may provide useful information regarding patients' psychosocial risk and tendency to access health services. Perspective: Clinical reference points based on the CSSI-24 total scores meaningfully differentiated youth with chronic pain on measures of emotional distress, functioning, parent catastrophizing and protective responses, and health care utilization. Assessing somatic symptoms could provide useful information regarding a pediatric patient's psychosocial risk, tendency to access health services, and need for enhanced care coordination.
Learn More >This paper reviews placebo-controlled randomized double-blind studies with erenumab for the prevention of migraine. Erenumab is a fully human monoclonal antibody (mAb), which specifically blocks the calcitonin gene-related peptide (GGRP) receptor. Areas covered: This manuscript was based on articles written in English located on PubMed found using the following search terms:episodic & chronic migraine, migraine prophylaxis & prevention, CGRP, CGRP receptor, CGRP receptor antagonist, erenumab, treatment failures, trigeminal nerve. Expert commentary: The primary endpoints in Phase II and III preventative episodic migraine trials have been reached successfully, and so have multiple secondary endpoints. Monthly subcutaneous injections of either erenumab 70 or 140 mg reduced mean monthly migraine days (MMDs) after a 3 and 6 months significantly greater than placebo when compared to baseline values with an onset of action within the first week. About 50% of subjects have a at least 50% reduction of MMDs. Several patient-reported outcome measures demonstrate improved quality of life with erenumab. This antibody shows efficacy in a prior treatment failure population. The tolerability of erenumab is good, which is reflected by low dropout rates in all erenumab clinical trials. Within the first year of treatment, no specific group or type class of adverse events were observed.
Learn More >Vasculitic peripheral neuropathy (VPN) is characterized by acute-to-subacute onset of painful sensory and motor disturbances that result from inflammatory obliteration of nerve blood vessels and subsequent ischaemic injury. Endoplasmic reticulum (ER) stress has been implicated in the pathogenesis of various peripheral neuropathies, and 4-phenylbutyric acid (4-PBA) is a chemical chaperone that inhibits ER stress signaling. We investigated the effects of 4-PBA on neuropathic pain associated with VPN induced by ischaemia-reperfusion (IR) and its underlying mechanisms. Male Sprague-Dawley rats were allocated to one of the following groups: sham, sham + 4-PBA, IR, and IR + 4-PBA. IR was achieved by occluding the femoral artery for 4 h followed by reperfusion. The behavioral parameters were assessed, and the expression of ER stress markers and nuclear factor (NF)-κB in sciatic nerves was measured. The behavioral data confirmed that VPN induced by IR leads to hindpaw mechano-allodynia and heat hyperalgesia as well as impaired hindpaw grip strength, indicating the development of neuropathic pain and debilitating symptoms of VPN. The molecular data revealed that VPN induced by IR activated ER stress sensors and effector molecules as well as NF-κB in the sciatic nerves, indicating the involvement of ER stress and NF-κB-mediated neuroinflammation. Notably, 4-PBA significantly reduced the expression of all these markers and improved all behavioral changes induced by IR. This study demonstrated that ER stress and NF-κB-mediated neuroinflammation contribute to VPN induced by IR and that 4-PBA has protective potential against neuropathic pain associated with VPN.
Learn More >Opioid use disorder (OUD) is a mounting public health problem with substantial morbidity and mortality. Stress involvement in the course of OUD is generally accepted, but little is understood about the underlying neurobiological mechanisms in part due to a lack of laboratory-based models for chronic stress exposure. Post-traumatic stress disorder (PTSD) may be construed as a psychopathological prototype of chronic stress owing to the essential diagnostic criteria of experiencing and reliving a stressful event(s). Literature search on OUD and PTSD neurobiology was undertaken and the relevant data were integrated within four key areas: (1) OUD and PTSD comorbidity, (2) neurobiological overlap between OUD and PTSD; (3) chronic opioids- and stress-induced alterations of the reward-, stress- (i.e., "anti-reward") and related circuits and (4) mechanistically informed treatments of OUD and/or PTSD. Our findings suggest that even in the absence of prior opioid exposure PTSD patients may be susceptible for the development of OUD by the reason of similar (to those induced by opioids) reward alterations that may be targeted for therapeutic interventions.
Learn More >Pain experienced during neonatal intensive care management can influence neurodevelopmental outcome and the somatosensory and/or emotional components of pain response in later life. Alterations in biological factors (e.g. peripheral and central somatosensory function and modulation, brain structure and connectivity) and psychosocial factors (e.g. gender, coping style, mood, parental response) that influence pain have been identified in children and young adults born very preterm or extremely preterm. Earlier gestational age at birth and cumulative pain exposure from tissue-breaking procedures and/or neonatal surgery influence the degree of change. In neonatal rodents, repeated needle insertion or hindpaw incision identify developmentally-regulated and activity-dependent long term alterations in nociceptive processing, and the efficacy of novel or current analgesic interventions can be compared. As prior neonatal experience and sex may influence current pain experience or the risk of persistent pain, these factors should be considered within the biopsychosocial assessment and formulation of pain in later life.
Learn More >Dermatological manifestations are common in systemic diseases, such as chronic kidney disease. The present study investigated the clinical features and possible influencing factors of pruritus in patients with chronic renal failure (CRF). A total of 382 inpatients were enrolled from the Department of Nephrology at The Second Affiliated Hospital of Chongqing Medical University. A total of 138 subjects were hemodialysis patients, 41 were peritoneal dialysis patients, and 203 were chronic renal failure patients. The patients' clinical performance was observed, and the data was recorded for analysis. The prevalence of pruritus in hemodialysis patients was greater than that in peritoneal dialysis patients. A total of 187 patients were accompanied by xerodermia and 109 patients had pruritus at the same time. With effective and regular dialysis, pruritus could be alleviated in 40% of patients. The intensity of pruritus in the enrolled patients ranged from mild itching to irritability during day and night periods. Moreover, pruritus was intermittent or persistent, and/or limited to generalized. Following treatment, 35% of patients had poor results. A significant difference was noted in the levels of serum urea nitrogen, creatinine, serum phosphorus, calcium × phosphorus, and parathyroid hormone (PTH) between patients with pruritus and non-pruritus. Xerodermia is a common skin manifestation in patients with chronic renal failure and is associated with the occurrence of pruritus. Local cold and heat stimulation can relieve pruritus to some extent, and adequate hemodialysis can also relieve itching.
Learn More >Genetics studies on the placebo hypoalgesic effect highlight a promising link between single nucleotide polymorphisms (SNPs) in the dopamine, opioid, and endocannabinoid genes and placebo hypoalgesia. However, epistasis and replication studies are missing. In this study, we expanded on previous findings related to the 3 SNPs in the opioid receptor mu subunit (OPRM1 rs1799971), catechol-O-methyltransferase (COMT rs4680), and fatty acid amide hydrolase (FAAH rs324420) genes associated with placebo hypoalgesia and tested the effect of a 3-way interaction on placebo hypoalgesia. Using 2 well-established placebo procedures (verbal suggestion and learning paradigm), we induced significant placebo hypoalgesic effects in 160 healthy participants. We found that individuals with OPRM1 AA combined with FAAH Pro/Pro and those carrying COMT met/met together with FAAH Pro/Pro showed significant placebo effects. Participants with COMT met/val alleles showed significant placebo effects independently of OPRM1 and FAAH allele combinations. Finally, the model that included the placebo procedure and genotypes predicted placebo responsiveness with a higher accuracy (area under the curve, AUC = 0.773) as compared to the SNPs alone indicating that genetic variants can only partially explain the placebo responder status. Our results suggest that the endogenous mu-opioid system with a larger activation in response to pain in the met/val allele carriers as well as the synergism between endogenous mu-opioid system and cannabinoids might play the most relevant role in driving hypoalgesic responses. Future epistasis studies with larger sample sizes will help us to fully understand the complexity of placebo effects and explain the mechanisms that underlie placebo responsiveness.
Learn More >: Chronic pain conditions of malignant and non-malignant etiology afflict a large group of the population and pose a vast economic burden on society. Intrathecal drug therapy is a viable treatment option in such patients who have failed conservative medical measures and less invasive pain management procedures. However, the clinical growth of intrathecal therapyin managing intractable chronic pain conditions continues to face many challenges and is likely underutilized secondary to its high-complexity and lack of understanding. : This review will briefly discuss the history of intrathecal drug delivery systems (IDDS), cerebrospinal fluid (CSF) flow dynamics, types of IDDS, indications and patient profile suitable for this therapy, and risks and complications related to IDDS. We will also discuss challenges faced by physicians utilizing this therapy and the future changes that are needed for making this treatment modality more efficacious. : IDDS offer an effective therapy for pain control in patients suffering from chronic intractable pain conditions. These devices provide a safer alternative to oral opioid medications with reduced systemic side effects. Adherence to best practices and continued clinical and basic science research is important to ensure continuing success of this therapy.
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