Browse by Audience
In the anterior lobe of the pituitary gland (AP), non-endocrine cells regulate hormone secretion by endocrine cells. However, the functions of non-endocrine cells in the AP during chronic pain are largely unclear. Here, we show that macrophages, but not folliculostellate (FS) cells, were selectively increased in the AP in the complete Freund's adjuvant (CFA)-induced chronic inflammatory pain model in rats. In addition, IL-1β expression was increased in the AP, and the IL-1β-immunopositive cells were identified as macrophages. On the other hand, increased macrophage density and IL-1β expression were not detected in a neuropathic pain model induced by partial sciatic nerve ligation (PSL). Furthermore, we found c-Fos expression specifically in the somatotrophs under the chronic inflammatory pain condition. Because IL-1β promotes growth hormone (GH) synthesis and release, our results suggest that AP macrophage contributes to GH release through IL-1βduring chronic inflammatory pain. .
Learn More >Capsaicin is a potent agonist of the TRPV1 channel, a transduction channel that is highly expressed in nociceptive fibers (pain fibers) throughout the peripheral nervous system. Given the importance of TRPV1 as one of several transduction channels in nociceptive fibers, much research has been focused on the potential therapeutic benefits of using TRPV1 antagonists for the management of pain. However, an antagonist has two limitations. First, an antagonist in principle generally only affects one receptor. Secondly, most antagonists must have an ongoing presence on the receptor to have an effect. Capsaicin overcomes both liabilities by disrupting peripheral terminals of nociceptive fibers that express TRPV1, and thereby affects all of the potential means of activating that pain fiber (not just TRPV1 function). This disruptive effect is dependent on the dose and can occur within minutes. Thus, unlike a typical receptor antagonist, continued bioavailability at the level of the receptor is not necessary. By disrupting the entire terminal of the TRPV1-expressing nociceptive fiber, capsaicin blocks all the activation mechanisms within that fiber, and not just TRPV1 function. Topical capsaicin, an FDA approved treatment for neuropathic pain, addresses pain from abnormal nociceptor activity in the superficial layers of the skin. Effects after a single administration are evident over a period of weeks to months, but in time are fully reversible. This review focuses on the rationale for using capsaicin by injection for painful conditions such as osteoarthritis (OA) and provides an update on studies completed to date.
Learn More >Although risk factors for new low back pain (LBP) episodes and acute-to-chronic transition have been identified, risk factors for flares of LBP remain largely unknown. This case-crossover study aimed to identify: (1) risk factors LBP flares and (2) whether risk factors differed when flare is defined by pain increase (pain-defined flare: PDF) or identified by participants according to a broader flare definition that considered emotions and coping (self-reported flare: SRF).
Learn More >Complex regional pain syndrome (CRPS) is a debilitating pain condition that often requires a multidisciplinary approach including medication, physical therapy, occupational therapy, psychological therapy, and interventional procedures to restore the patient's quality of life. This article reviews the interventional treatments for pain resulting from CRPS.
Learn More >Since the introduction of insulin almost a century ago, more than 80 peptide drugs have reached the market for a wide range of diseases, including diabetes, cancer, osteoporosis, multiple sclerosis, HIV infection and chronic pain. In this Perspective, we summarize key trends in peptide drug discovery and development, covering the early efforts focused on human hormones, elegant medicinal chemistry and rational design strategies, peptide drugs derived from nature, and major breakthroughs in molecular biology and peptide chemistry that continue to advance the field. We emphasize lessons from earlier approaches that are still relevant today as well as emerging strategies such as integrated venomics and peptide-display libraries that create new avenues for peptide drug discovery. We also discuss the pharmaceutical landscape in which peptide drugs could be particularly valuable and analyse the challenges that need to be addressed for them to reach their full potential.
Learn More >Morphine-induced itch is a very common and debilitating side effect that occurs in laboring women who receive epidural analgesia and in patients who receive spinal morphine for relief of perioperative pain. Although antihistamines are still widely prescribed for the treatment of morphine-induced itch, their use is controversial because the cellular basis for morphine-induced itch remains unclear. Here, we used animal models and show that neuraxial morphine causes itch through neurons and not mast cells. In particular, we found that spinal dynorphin (Pdyn) neurons are both necessary and sufficient for morphine-induced itch in mice. Agonism of the kappa-opioid receptor alleviated morphine-induced itch in mice and nonhuman primates. Thus, our findings not only reveal that morphine causes itch through a mechanism of disinhibition but also challenge the long-standing use of antihistamines, thereby informing the treatment of millions worldwide.
Learn More >Several randomized controlled trials have implemented cognitive behavioral therapy for insomnia (CBT-I) for patients with comorbid insomnia and chronic pain. This systematic review and meta-analysis investigated the effectiveness of CBT-I on patient-reported sleep, pain, and other health outcomes (depressive symptoms, anxiety symptoms, and fatigue) in patients with comorbid insomnia and chronic non-cancer pain. A systematic literature search was conducted using eight electronic databases. Upon duplicate removal, 6374 records were screened against the inclusion criteria. Fourteen randomized controlled trials were selected for the review, with twelve (N = 762 participants) included in the meta-analysis. At post-treatment, significant treatment effects were found on global measures of sleep (standardized mean difference = 0.89), pain (0.20), and depressive symptoms (0.44). At follow-up (up to 12 mo), CBT-I significantly improved sleep (0.56). Using global measures of sleep, we found a probability of 81% and 71% for having better sleep after CBT-I at post-treatment and final follow-up, respectively. The probability of having less pain after CBT-I at post-treatment and final follow-up was 58% and 57%, respectively. There were no statistically significant effects on anxiety symptoms and fatigue at either assessment point. Future trials with sufficient power, longer follow-up periods, and inclusion of CBT for pain components are warranted.
Learn More >Although several questionnaires assessing fear of movement exist, it still is challenging to identify individuals who might benefit more from exposure for chronic pain than from other psychological approaches, and vice versa. Psychological approaches for chronic pain cannot advance towards the often called-for "tailored approaches" because of limited knowledge about treatment predictors. Our aim was to evaluate the additional predictive value of avoidance behavior based on behavioral observation.
Learn More >Parents have a vital influence over their child's chronic pain treatment and management. Graded exposure in-vivo treatment (GET) is emerging as a promising intervention for youth with chronic pain. Yet, little is known about how parents perceive GET and its impact on their child's pain condition. This study aimed to characterize caregivers' experiences over the course of their child's GET using longitudinal coding and thematic analysis of parent narratives.
Learn More >To comprehensively describe the quality of conduct, reporting, and publication integrity characteristics for all trials included in a large Cochrane review, comparing those published by presumed predatory publishers with those published by non-predatory publishers.
Learn More >