Browse by Audience
Cortical long-term potentiation (LTP) serves as a cellular model for chronic pain. As an important subtype of adenylyl cyclases (ACs), adenylyl cyclase subtype 1 (AC1) is critical for the induction of cortical LTP in the anterior cingulate cortex (ACC). Genetic deletion of AC1 or pharmacological inhibition of AC1 blocked behavioral allodynia in animal models of neuropathic and inflammatory pain. Our previous experiments have identified a lead candidate AC1 inhibitor, NB001, which is highly selective for AC1 over other AC isoforms, and found that NB001 is effective in inhibiting behavioral allodynia in animal models of chronic neuropathic and inflammatory pain. However, previous experiments were carried out in adult male animals. Considering the potential gender difference as an important issue in researches of pain and analgesia, we investigated the effect of NB001 in female chronic pain animal models. We found that NB001, when administered orally, has an analgesic effect in female animal models of neuropathic and inflammatory pain without any observable side effect. Genetic deletion of AC1 also reduced allodynia responses in models of neuropathic pain and chronic inflammation pain in adult female mice. In brain slices of adult female mice, bath application of NB001(20 μM) blocked the induction of LTP in ACC. Our results indicate that calcium-stimulated AC1 is required for injury-related cortical LTP and behavioral allodynia in both sexes of adult animals, and NB001 can be used as a potential therapeutic drug for treating neuropathic and inflammatory pain in man and woman.
Learn More >Some individuals with chronic pain experience improvement in their pain with treatment, whereas others do not. The neurobiological reason is unclear, but an understanding of brain structure and functional patterns may provide insights into pain's responsivity to treatment. In this investigation, we used magnetic resonance imaging (MRI) techniques to determine grey matter density alterations on resting functional connectivity (RFC) strengths between pain responders and nonresponders in patients with complex regional pain syndrome. Brain metrics of pediatric patients at admission to an intensive pain rehabilitative treatment program were evaluated. Pain responders reported significant pain improvement at discharge and/or follow-up whereas nonresponders reported no improvements in pain, increases in pain, or emergence of new pain symptoms. The pain (responder/nonresponder) groups were compared with pain-free healthy controls to examine predictors of pain responder status via brain metrics. Our results show: (1) on admission, pain nonresponders had decreased grey matter density (GMD) within the nucleus accumbens (NAc) and reduced RFC strength between the NAc and the dorsolateral prefrontal cortex vs. responders; (2) Connectivity strength was positively correlated with change in pain intensity from admission to discharge; (3) Compared with pain-free controls, grey matter and RFC differences emerged only among pain nonresponders; and (4) Using a discriminative model, combining GMD and RFC strengths assessed at admission showed the highest prediction estimate (87%) on potential for pain improvement, warranting testing in a de novo sample. Taken together, these results support the idea that treatment responsiveness on pain is underpinned by concurrent brain structure and resting brain activity.
Learn More >Multimodal treatment is recognized as the optimal paradigm for the management of chronic pain (CP). Careful balance between pharmacological and physical/psychological approaches is thus desirable but can be easily disrupted.
Learn More >We previously reported promising results for a 4-month patient-centered voluntary opioid tapering study. Key questions remain about the durability of effects and possible risks after opioid reduction. We provide the longest follow-up data to date for prospective opioid tapering: 2- to 3-year follow-up for pain intensity and daily opioid use in a subset of patients from our original 4-month opioid tapering study.
Learn More >Spinal cord injury (SCI) is a devastating injury to the central nervous system in which 60 to 80% of patients experience chronic pain. Unfortunately, this pain is notoriously difficult to treat, with few effective options currently available. Patients are also commonly faced with various compounding injuries and medical challenges, often requiring frequent hospitalization and antibiotic treatment. Change in the gut microbiome from the "normal" state to one of imbalance, referred to as gut dysbiosis, has been found in both patients and rodent models following SCI. Similarities exist in the bacterial changes observed after SCI and other diseases with chronic pain as an outcome. These changes cause a shift in the regulation of inflammation, causing immune cell activation and secretion of inflammatory mediators that likely contribute to the generation/maintenance of SCI pain. Therefore, correcting gut dysbiosis may be used as a tool towards providing patients with effective pain management and improved quality of life.
Learn More >To systematically review the literature to assess whether genetic polymorphisms affect orofacial pain sensitivity in healthy individuals and in patients with chronic orofacial pain disorders.
Learn More >In recent months, with the emergence of the COVID-19 pandemic, the American College of Surgeons and the U.S. Centers for Disease Control and Prevention officially recommended the delay of nonemergency procedures until the public health crisis is resolved. Deferring elective joint replacement surgeries for an unknown period is likely to decrease the incidence of infection with SARS-CoV-2 but is likely to have detrimental effects in individuals suffering from chronic knee pain. These detrimental effects extend beyond the discomfort of osteoarthritis (OA) and the inconvenience of rescheduling surgery. Disabling pain is a driving factor for individuals to seek medical intervention, including pharmacological palliative treatment and surgical procedures. The need for surgical intervention due to chronic pain as for knee and hip replacement is now put on hold indefinitely because access to surgical care has been limited. Although a moderate delay in surgical intervention may not produce a significant progression of OA within the knee, it could lead to muscle wasting due to immobility and exacerbate comorbidities, making rehabilitation more challenging. Importantly, it will have an impact on comorbidities driven by OA severity, notably decreased quality of life and depression. These patients with unremitting pain become increasingly susceptible to substance use disorders including opioids, alcohol, as well as prescription and illegal drugs. Appreciation of this downstream crisis created by delayed surgical correction requires aggressive consideration of nonsurgical, nonopiate supported interventions to reduce the morbidity associated with these delays brought upon by the currently restricted access to joint repair.
Learn More >To describe the pain characteristics of five index chronic overlapping pain conditions (COPCs) and to assess each COPC separately in order to determine whether the presence of comorbid COPCs is associated with bodily pain distribution, pain intensity, pain interference, and high-impact pain of the index COPC.
Learn More >Pain arising from musculoskeletal disorders such as arthritis is one of the leading causes of disability. Whereas the past 20-years has seen an increase in targeted therapies for rheumatoid arthritis (RA), other arthritis conditions, especially osteoarthritis, remain poorly treated. Although modulation of central pain pathways occurs in chronic arthritis, multiple lines of evidence indicate that peripherally driven pain is important in arthritic pain. To understand the peripheral mechanisms of arthritic pain, various and models have been developed, largely in rodents. Although rodent models provide numerous advantages for studying arthritis pathogenesis and treatment, the anatomy and biomechanics of rodent joints differ considerably to those of humans. By contrast, the anatomy and biomechanics of joints in larger animals, such as dogs, show greater similarity to human joints and thus studying them can provide novel insight for arthritis research. The purpose of this article is firstly to review models of arthritis and behavioral outcomes commonly used in large animals. Secondly, we review the existing models and assays used to study arthritic pain, primarily in rodents, and discuss the potential for adopting these strategies, as well as likely limitations, in large animals. We believe that exploring peripheral mechanisms of arthritic pain in large animals has the potential to reduce the veterinary burden of arthritis in commonly afflicted species like dogs, as well as to improve translatability of pain research into the clinic.
Learn More >