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The study aims were 1) to investigate the direction of mutual inhibitory pathways on itch intensity by utilizing conditioned pain modulation paradigms for pain and itch attenuation and 2) to explore whether itch severity is affected by the individual pain sensitivity profile, as well as pain scores reported during the tests and the past week.
Learn More >Presents an obituary of Ronald Melzack (1929-2019). Melzack died on Sunday, December 22, 2019, at 10:00 p.m. News of his death spread like wildfire through the network of long-time friends and colleagues who had heard of his imminent passing. At that moment, the world lost a compassionate and caring soul, an advocate for chronic pain sufferers around the globe, and a giant in the international pain community. He is survived by his wife of 59 years, Lucy (née Birch), their son, Joel, and daughter, Lauren. Ron is known for four major accomplishments: establishing Canada's first multidisciplinary pain center at the Montreal General Hospital with neurosurgeon colleague and friend the late Joseph Stratford; the 1965 publication, in , of the gate control theory of pain with the late Patrick Wall; development of the McGill Pain Questionnaire and its derivatives; and later in his career, at 60 years of age, publication of the neuromatrix theory of pain, moving the field beyond the spinal gating mechanism into the brain. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
Learn More >Chronic morphine-induced antinociceptive tolerance is a major unresolved issue in clinical practices, which is associated with microglia activation in the spinal cord. E3 ubiquitin ligase Pellino1 (Peli1) is known to be an important microglia-specific regulator. However, it is unclear whether Peli1 is involved in morphine tolerance. Here, we found that Peli1 levels in the spinal cord were significantly elevated in morphine tolerance mouse model. Notably, Peli1 was expressed in a great majority of microglia in the spinal dorsal horn, while downregulation of spinal Peli1 attenuated the development of morphine tolerance and associated hyperalgesia. Our biochemical data revealed that morphine tolerance-induced increase in Peli1 was accompanied by spinal microglia activation, activation of mitogen-activated protein kinase (MAPK) signaling, and production of proinflammatory cytokines. Peli1 additionally was found to promote K63-linked ubiquitination of tumor necrosis factor receptor-associated factor 6 (TRAF6) in the spinal cord after repeated morphine treatment. Furthermore, knocking down Peli1 in cultured BV2 microglial cells significantly attenuated inflammatory reactions in response to morphine challenge. Therefore, we conclude that the upregulation of Peli1 in the spinal cord plays a curial role in the development of morphine tolerance via Peli1-dependent mobilization of spinal microglia, activation of MAPK signaling, and production of proinflammatory cytokines. Modulation of Peli1 may be a potential strategy for the prevention of morphine tolerance.
Learn More >Pain is the most frequent cause triggering patients to visit a physician. The worldwide incidence of chronic pain is in the range of 20% of adults, and chronic pain conditions are frequently associated with several comorbidities and a drastic decrease in patients' quality of life. Although several approved analgesics are available, such therapy is often not satisfying due to insufficient efficacy and/or severe side effects. Therefore, novel strategies for the development of safe and highly efficacious pain killers are urgently needed. To reach this goal, it is necessary to clarify the causes and signal transduction cascades underlying the onset and progression of the different types of chronic pain. The papers in this Special Issue cover a wide variety of mechanisms involved in different pain types such as inflammatory, neuropathic or cancer pain. Therefore, the results summarized here might contribute to a better understanding of the mechanisms in chronic pain and thereby to the development of novel therapeutic strategies for pain patients.
Learn More >Many patients who require migraine preventive treatment have not been able to tolerate or have not responded to multiple previous preventive medications. We aimed to assess the safety and efficacy of galcanezumab, an antibody to calcitonin gene-related peptide, in patients with migraine who had not benefited from preventive medications from two to four categories.
Learn More >Long-term opioid therapy has the potential for serious adverse outcomes and is often used in a vulnerable population. Because adverse effects or failure to maintain benefits is common with long-term use, opioid taper or discontinuation may be indicated in certain patients. Concerns about the adverse individual and population effects of opioids have led to numerous strategies aimed at reductions in prescribing. Although opioid reduction efforts have had generally beneficial effects, there have been unintended consequences. Abrupt reduction or discontinuation has been associated with harms that include serious withdrawal symptoms, psychological distress, self-medicating with illicit substances, uncontrolled pain, and suicide. Key questions remain about when and how to safely reduce or discontinue opioids in different patient populations. Thus, health care professionals who reduce or discontinue long-term opioid therapy require a clear understanding of the associated benefits and risks as well as guidance on the best practices for safe and effective opioid reduction. An interdisciplinary panel of pain clinicians and one patient advocate formulated recommendations on tapering methods and ongoing pain management in primary care with emphasis on patient-centered, integrated, comprehensive treatment models employing a biopsychosocial perspective.
Learn More >Compared to the field of anxiety research, the use of fear conditioning paradigms for studying chronic pain is relatively novel. Developments in identifying the neural correlates of pain-related fear are important for understanding the mechanisms underlying chronic pain and warrant synthesis to establish the state-of-the-art. Using effect-size signed differential mapping, this meta-analysis combined nine MRI studies and compared the overlap in these correlates of pain-related fear to those of other non-pain-related conditioned fears (55 studies). Pain-related fear was characterized by neural activation of the supramarginal gyrus, middle temporal gyrus, inferior/middle frontal gyri, frontal operculum and insula, pre-/post-central gyri, medial frontal and (para-)cingulate cortex, hippocampus, thalamus, and putamen. There were differences with other non-pain-related conditioned fears, specifically in the inferior frontal gyrus, medial superior frontal gyrus, post-central gyrus, middle temporal gyrus, parieto-occipital sulcus, and striatum. We conclude that pain-related and non-pain-related conditioned fears recruit overlapping but distinguishable networks, with potential implications for understanding the mechanisms underlying different psychopathologies.
Learn More >Long-term opioid use has negative health care consequences. Opioid-naïve adults are at risk for prolonged and persistent opioid use after surgery. While these outcomes have been examined in some adolescent and teenage populations, little is known about the risk of prolonged and persistent postoperative opioid use after common surgeries compared to children who do not undergo surgery and factors associated with these issues among pediatric surgical patients of all ages.
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