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Adolescent cannabinoid exposure has been shown to alter cognitive, reward-related, and motor behaviors as well as mesocorticolimbic dopamine (DA) function in adult animals. Pain is also influenced by mesocorticolimbic DA function, but it is not known whether pain or cannabinoid analgesia in adults is altered by early exposure to cannabinoids.
Learn More >Adenylyl cyclase type 1 (AC1) is involved in signaling for chronic pain sensitization in the central nervous system and is an emerging target for the treatment of chronic pain. AC1 and a closely related isoform AC8 are also implicated to have roles in learning and memory signaling processes. Our team has carried out cellular screening for inhibitors of AC1 yielding a pyrazolyl-pyrimidinone scaffold with low micromolar potency against AC1 and selectivity AC8. Structure-activity relationship (SAR) studies led to analogues with cellular IC values as low as 0.25 μM, selectivity AC8 and other AC isoforms as well as other common neurological targets. A representative analogue displayed modest antiallodynic effects in a mouse model of inflammatory pain. This series represents the most potent and selective inhibitors of Ca/calmodulin-stimulated AC1 activity to date with improved drug-like physicochemical properties making them potential lead compounds for the treatment of inflammatory pain.
Learn More >To assess painful diabetic neuropathy (PDN) as a cause for refractory ear pain in type 2 diabetics.
Learn More >Over 50% of adolescents with chronic pain report comorbid sleep disturbances (e.g., difficulties with falling asleep), which is associated with increased pain-related disability and poorer quality of life. However, limited longitudinal data are available to understand how sleep disturbance may impact response to psychological treatment. Our primary hypothesis was that baseline sleep disturbances would significantly modify how adolescents responded to an internet-delivered psychological intervention for chronic pain in terms of outcome trajectories. The sample included 85 adolescents, 12 to 17 years, with chronic pain recruited from a multidisciplinary pain clinic and headache clinic who received access to an internet-delivered psychological intervention for chronic pain. Baseline sleep assessment included actigraphy monitoring for 7 days and survey measures. Outcomes were assessed at baseline, 8 weeks, and 3 months including core pain-related outcomes, executive functioning, fatigue, positive and negative affect. Results demonstrated that greater baseline insomnia and poorer sleep quality was associated with worse outcome trajectories for pain-related disability, depression, anxiety, fatigue, negative affect, and executive functioning. Findings extend the limited studies that examine how sleep disturbance may modify effectiveness of psychological treatments for adolescent chronic pain and emphasize the importance of treating comorbid sleep disturbance. This trial was registered at clinicaltrials.gov (NCT04043962). Perspective: Our study suggests that sleep deficiency, in particular insomnia and poor sleep quality, may modify the effectiveness of psychological treatments for chronic pain, highlighting the urgent need to screen youth for sleep problems prior to initiating treatment, and to consider implementation of sleep-specific treatments such as cognitive-behavioral therapy for insomnia.
Learn More >Chronic prurigo (CPG) is characterized by intensive itch and nerve-neuropeptide-mast cell interactions. The role of some neuropeptides such as cortistatin and its receptor MRGPRX2 in CPG is poorly investigated.
Learn More >Functional improvement is a critical outcome for individuals living with chronic pain. Graded exposure treatment has been associated with statistically significant improvements in functional outcomes for youth with chronic pain by targeting pain-related fear and avoidance.
Learn More >Recent scientific evidence suggests a link between migraine and brain energy metabolism. In fact, migraine is frequently observed in mitochondrial disorders. We studied 46 patients affected by mitochondrial disorders, through a headache-focused semi-structured interview, to evaluate the prevalence of migraine among patients affected by mitochondrial disorders, the possible correlations between migraine and neuromuscular genotype or phenotype, comorbidities, lactate acid levels and brain magnetic resonance spectroscopy. We explored migraine-related disability, analgesic and prophylactic treatments. Diagnoses were achieved according to International Classification of Headache Disorders, 3rd edition. Lifetime prevalence of migraine was 61% (28/46), with high values in both sexes (68% in females, 52% in males) and higher than the values found in both the general population and previous literature. A maternal inheritance pattern was reported in 57% of cases. MIDAS and HIT6 scores revealed a mild migraine-related disability. The high prevalence of migraine across different neuromuscular phenotypes and genotypes suggests that migraine itself may be a common clinical manifestation of brain energy dysfunction. Our results provide new relevant indications in favour of migraine as the result of brain energy unbalance.
Learn More >To use data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2019 (GBD 2019) to estimate mortality and disability trends for the population aged ≥70 and evaluate patterns in causes of death, disability, and risk factors.
Learn More >Immunogenicity of erenumab, a human anti-calcitonin gene-related peptide receptor monoclonal antibody developed for migraine prevention, has been evaluated throughout clinical development.
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