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α9-Containing nicotinic acetylcholine receptors (nAChRs) are key targets for the treatment of neuropathic pain. α-Conotoxin RgIA4 is a peptide antagonist of human α9α10 nAChRs with high selectivity. However, structural rearrangement reveals a potential liability for clinical applications. We herein report our designer RgIA analogues stabilized by methylene thioacetal as nonopioid analgesic agents. We demonstrate that replacing disulfide loop I [Cys-Cys] with methylene thioacetal in the RgIA skeleton results in activity loss, whereas substitution of loop II [Cys-Cys] can be accommodated. The lead molecule, RgIA-5524, exhibits highly selective inhibition of α9α10 nAChRs with an IC of 0.9 nM and much reduced degradation in human serum. studies showed that RgIA-5524 relieves chemotherapy-induced neuropathic pain in wild type but not α9 knockout mouse models, demonstrating that α9-containing nAChRs are necessary for the therapeutic effects. This work highlights the application of methylene thioacetal as a disulfide surrogate in conotoxin-based, disulfide-rich peptide drugs.
Learn More >In 2016, the Centers for Disease Control and Prevention analyzed the National Health Interview Survey data and found that the occurrence of chronic pain and high-impact chronic pain in the USA was 20.4% and 8%, respectively. Group-based Pain Management Programs have been viewed as significant treatments aiding patients with self-management of chronic pain. The onset of coronavirus disease 2019 (COVID-19) at the beginning of 2020, widely eliminated the in-person Group-based Pain Management Programs. The exploration of therapeutic contextual factors such as the therapeutic alliance and group dynamics in telehealth Group-based Pain Management Programs appears warranted for which reason the Therapeutic Group Context Questionnaire was developed.
Learn More >Physicians and patients report frustration after primary care visits for chronic pain. The need to shift between multiple clinical topics to address competing demands during visits may contribute to this frustration.
Learn More >Current prophylactic drugs for cluster headache are associated with limited efficacy, serious side effects and poor tolerability. Greater occipital nerve injection (GON-injection) has been proven effective and safe as a single, one-time injection in episodic (ECH), and to a lesser extent, chronic cluster headache (CCH). We aim to analyse the effectiveness and safety of repeated GON-injections in medically intractable chronic cluster headache (MICCH).
Learn More >Mitragynine (MG) is the most abundant alkaloid component of the psychoactive plant material "kratom", which according to numerous anecdotal reports shows efficacy in self-medication for pain syndromes, depression, anxiety, and substance use disorders. We have developed a synthetic method for selective functionalization of the unexplored C11 position of the MG scaffold (C6 position in indole numbering) via the use of an indole-ethylene glycol adduct and subsequent iridium-catalyzed borylation. Through this work we discover that C11 represents a key locant for fine-tuning opioid receptor signaling efficacy. 7-Hydroxymitragynine (7OH), the parent compound with low efficacy on par with buprenorphine, is transformed to an even lower efficacy agonist by introducing a fluorine substituent in this position (11-F-7OH), as demonstrated in vitro at both mouse and human mu opioid receptors (mMOR/hMOR) and in vivo in mouse analgesia tests. Low efficacy opioid agonists are of high interest as candidates for generating safer opioid medications with mitigated adverse effects.
Learn More >Lockdown measures due to the COVID-19 pandemic have led to lifestyle changes, which in turn may have an impact on the course of headache disorders. We aimed to assess changes in primary headache characteristics and lifestyle factors during the COVID-19 lockdown in Germany using digital documentation in the mobile application (app) M-sense.
Learn More >Genetic variation in the catechol-O-methyltransferase (COMT) gene is associated with sensitivity to both acute experimental pain and chronic pain conditions. Four single nucleotide polymorphisms (SNPs) have traditionally been used to infer three common haplotypes designated as low, average and high pain sensitivity (LPS, APS and HPS) and are reported to affect both COMT enzymatic activity and pain sensitivity. One mechanism that may partly explain individual differences in sensitivity to pain is Conditioned Pain Modulation (CPM). We hypothesized that variation in CPM may have a genetic basis.
Learn More >Many online interventions for paediatric chronic pain have been developed and evaluated. In accordance with the biopsychosocial model, the recommended treatment approach for chronic pain is multidisciplinary. Despite this, multidisciplinary components within existing online interventions have not been examined. The objective of the present review was to summarise and evaluate the content of existing online interventions for paediatric chronic pain by mapping intervention content to evidence-based guidelines for chronic pain management.
Learn More >Chronic pain in children and adolescents gives rise to high health care costs. Successful treatment is supposed to reduce the economic burden. The objective of this study was to determine the changes in health care utilization and expenditures from one year before (Pre) intensive interdisciplinary pain treatment (IIPT) to the first (Post 1) and second (Post 2) years after discharge in a sample of pediatric chronic pain patients.
Learn More >Pain neuroscience education (PNE) has received increasing research attention demonstrating beneficial effects on pain-related outcomes in adults. Conversely, studies on the effectiveness of PNE in children are scarce.
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