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The biopsychosocial model claims that illness is generated by biological, psychological, and social factors. The nocebo response, particularly nocebo hyperalgesia, is an excellent model and approach to understand these effects and their psychophysiological underpinnings, as nocebos are made of negative psychological and social factors, such as negative expectations and social interactions. There is today experimental evidence that nocebos can create symptoms and illness from nothing, in particular pain, whereby a combination of biological, psychological and social factors interact with each other in the generation of the global painful experience. Several biochemical pathways have been identified, e.g. cholecystokinin and cyclooxygenase, and the activation of these mechanisms has been specifically investigated in the field of pain, analgesia and hyperalgesia. The study of placebo and nocebo oxygen at high-altitude has been crucial to unravel these mechanisms, as reduction of oxygen pressure (hypoxia) leads to headache pain. Indeed, the investigation of oxygen-related conditions, such as hypoxia, represents today an excellent approach to understand how nocebos can contribute to generate illness and pain. In this review we discuss old and new findings that help us better understand the interplay between biology and psychology.
Learn More >The Transient Receptor Potential Ankyrin TRPA channels are Ca-permeable non-selective cation channels remarkably conserved through the animal kingdom. Mammals have only one member, TRPA1, which is widely expressed in sensory neurons and in non-neuronal cells (such as epithelial cells and hair cells). TRPA1 owes its name to the presence of 14 ankyrin repeats located in the N-terminus of the channel, an unusual structural feature that may be relevant to its interactions with intracellular components. TRPA1 is primarily involved in the detection of an extremely wide variety of exogenous stimuli that may produce cellular damage. This include a plethora of electrophilic compounds that interact with nucleophilic amino acid residues in the channel, and many other chemically-unrelated compounds whose only common feature seems to be their ability to partition in the plasma membrane. TRPA1 has been reported to be activated by cold, heat and mechanical stimuli, and its function is modulated by multiple factors, including Ca, trace metals, pH, and reactive oxygen, nitrogen and carbonyl species. TRPA1 is involved in acute and chronic pain, inflammation, plays a role in the pathophysiology of nearly all organ systems and is an attractive target for the treatment of related diseases. Here we review the current knowledge about the mammalian TRPA1 channel, linking its unique structure, widely tuned sensory properties and complex regulation to its roles in multiple pathophysiological conditions.
Learn More >Despite large efforts to test analgesics in animal models, only a handful of new pain drugs have shown efficacy in patients. Here, we report a systematic review and meta-analysis of preclinical studies of the commercially successful drug pregabalin. Our primary objective was to describe design characteristics and outcomes of studies testing the efficacy of pregabalin in behavioral models of pain. Secondarily, we examined the relationship between design characteristics and effect sizes. We queried MEDLINE, Embase, and BIOSIS to identify all animal studies testing the efficacy of pregabalin published before January 2018 and recorded experimental design elements addressing threats to validity and all necessary data for calculating effect sizes, expressed as the percentage of maximum possible effect. We identified 204 studies (531 experiments) assessing the efficacy of pregabalin in behavioral models of pain. The analgesic effect of pregabalin was consistently robust across every etiology/measure tested, even for pain conditions that have not responded to pregabalin in patients. Experiments did not generally report using design elements aimed at reducing threats to validity, and analgesic activity was typically tested in a small number of model systems. However, we were unable to show any clear relationships between preclinical design characteristics and effect sizes. Our findings suggest opportunities for improving the design and reporting of preclinical studies in pain. They also suggest that factors other than those explored in this study may be more important for explaining the discordance between outcomes in animal models of pain and those in clinical trials.
Learn More >The definition of chronic migraine has long been debated. Recently, it was suggested to define subjects with at least 8/migraine days as chronic migraine; that is, incorporating so-called high frequency episodic migraine (eight or more migraine days but less than 15 headache days per month).
Learn More >Opioids are commonly used for postoperative pain management in spine surgery. However, few guidelines exist for appropriate prescribing in the acute postoperative phase of care. We identify risk factors for inpatient (IP) opioid use and examine relationships between IP requirements and discharge (DC) opioid prescriptions.
Learn More >Transcutaneous electrical nerve stimulation (TENS), manual acupuncture (MA), and spinal cord stimulation (SCS) are used to treat a variety of pain conditions. These non-pharmacological treatments are often thought to work through similar mechanisms, and thus should have similar effects for different types of pain. However, it is unclear if each of these treatments work equally well on each type of pain condition. The purpose of this study was to compared the effects of TENS, MA, and SCS on neuropathic, inflammatory, and non-inflammatory pain models.
Learn More >Chronic pain is a significant public health problem that is associated with several negative health outcomes, including increased health care cost, decreased productivity, and prescription opioid misuse. Although efforts have been made to curb the growing opioid epidemic in the United States, further research is needed to better understand individual difference factors that may be associated with greater pain and opioid misuse. Lower levels of health literacy, defined as the ability to obtain, understand, and use health information to make important decisions regarding health and medical care, has been associated with several chronic illnesses. Yet little work has examined the relationship between health literacy, pain, and opioid misuse among individuals with chronic pain.
Learn More >Fremanezumab, a fully humanized monoclonal antibody targeting calcitonin gene-related peptide, has demonstrated efficacy for the preventive treatment of migraine in adults.
Learn More >Cortical areas including the anterior cingulate cortex (ACC) play critical roles in different types of chronic pain. Most of previous studies focus on the sensory inputs from somatic areas, and less information about plastic changes in the cortex for visceral pain. In this study, chronic visceral pain animal model was established by injection with zymosan into the colon of adult male C57/BL6 mice. Whole cell patch-clamp recording, behavioral tests, Western blot, and Cannulation and ACC microinjection were employed to explore the role of adenylyl cyclase 1 (AC1) in the ACC of C57/BL6 and AC1 knock out (AC1 KO) mice. Integrative approaches were used to investigate possible changes of neuronal adenylyl cyclase 1 (AC1) in the ACC after the injury. We found that AC1, a key enzyme for pain-related cortical plasticity, was significantly increased in the ACC in an animal model of irritable bowel syndrome. Inhibiting AC1 activity by a selective AC1 inhibitor NB001 significantly reduced the upregulation of AC1 protein in the ACC. Furthermore, we found that AC1 is required for NMDA GluN2B receptor upregulation and increases of NMDA receptor-mediated currents. These results suggest that AC1 may form a positive regulation in the cortex during chronic visceral pain. Our findings demonstrate that the upregulation of AC1 protein in the cortex may underlie the pathology of chronic visceral pain; and inhibiting AC1 activity may be beneficial for the treatment of visceral pain.
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