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Deprescribing is the systematic process of discontinuing medications when the harms outweigh the benefits. This study aimed to identify barriers and facilitators in people with chronic non-cancer pain when deprescribing opioid analgesics, and their views on resources that assist with deprescribing.
Learn More >To develop safer and potent analgesics, we designed, synthesized, and evaluated a new series of benzylaminofentanyl derivates as bifunctional μ opioid receptor (MOR) and σ receptor (σR) ligands. Compound 68 (Tao-191) showed desirable MOR agonism (K = 6.5 nΜ; EC = 48.5 nΜ, E = 66.3%) and σR antagonism (K = 35.7 nM) in vitro, and exerted powerful analgesic effects in the abdominal constriction test (ED = 0.32 mg/kg, in mice), formalin-induced pain test (phase II, ED = 2.26 mg/kg, in rats), and paclitaxel-induced neuropathic pain model (ED = 0.30 mg/kg, in mice). The contributions of MOR and σR to its antinociceptive effect were verified by combined administration with the MOR antagonist naloxone and the σR agonist PRE-084, respectively. At equianalgesic doses, compound 68 induced fewer MOR-related side effects-including physical and psychological dependence, respiratory depression, constipation, and acute hyperlocomotion-than fentanyl. The results provide a rationale for further exploration of the action and safety of dual MOR/σR ligands as a promising avenue for the development of potent and safe analgesics.
Learn More >To compare the effects of virtual reality (VR) and motor control (MC) exercises.
Learn More >A newly deorphanized G protein-coupled receptor, GPR171, is found to be highly expressed within the periaqueductal gray, a pain-modulating region in the brain. Our recent research has shown that a GPR171 agonist increases morphine antinociception in male mice and opioid signaling in vitro. The objective of this study was to evaluate the effects of combination treatment in females as well as whether chronic treatment can be used without exacerbating morphine-induced tolerance and withdrawal in female and male mice. Our results demonstrate that activation of GPR171 with an agonist attenuates morphine tolerance in both female and male mice on the tail-flick test, but not the hotplate test. Importantly, the GPR171 agonist in combination with morphine does not exacerbate morphine-induced tolerance and withdrawal during long-term morphine treatment. Taken together, these data suggest that the GPR171 agonist may be combined with morphine to maintain antinociception while reducing the dose of morphine and therefore reducing side effects and abuse liability. The outcome of this study is clearly an important step toward understanding the functional interactions between opioid receptors and GPR171 and developing safer therapeutics for long-term pain management.
Learn More >Chronic post-surgical pain (CPSP) prevalence has not changed over the past decades what questions the efficacy of preventive strategies. Regional analgesia is used to control acute pain, but preventive effect on CPSP remains debated. Failures and future application of regional analgesia to prevent transition from acute to chronic pain will be discussed.
Learn More >Repeated skin contact to detergents causes chronic irritant contact dermatitis (ICD) associated with itch sensation and eczema. However, the mechanisms of detergent-induced ICD are poorly understood. Here, we established a new murine model of detergent-induced ICD with H1-antihistamine-refractory itch.
Learn More >MAO-B inhibitors have been implicated to reverse neuropathic pain behaviors. Our previous study has demonstrated that KDS2010 (KDS), a newly developed reversible MAO-B inhibitor, could attenuate Paclitaxel (PTX)-induced tactile hypersensitivity in mice through suppressing reactive oxidant species (ROS)-decreased inhibitory GABA synaptic transmission in the spinal cord. In this study, we evaluated the analgesic effect of KDS under a new approach, in which KDS acts on dorsal horn sensory neurons to reduce excitatory transmission. Oral administration of KDS effectively enhanced mechanical thresholds in the spinal nerve ligation (SNL) induced neuropathic pain in rats. Moreover, we discovered that although treatment with KDS increased brain-derived neurotrophic factor (BDNF) levels, KDS inhibited Tropomyosin receptor kinase B (TrkB) receptor activation, suppressing increased p-NR2B-induced hyperexcitability in spinal dorsal horn sensory neurons after nerve injury. In addition, KDS showed its anti-inflammatory effects by reducing microgliosis and astrogliosis and the activation of MAPK and NF-ᴋB inflammatory pathways in these glial cells. The levels of ROS production in the spinal cords after the SNL procedure were also decreased with KDS treatment. Taken together, our results suggest that KDS may represent a promising therapeutic option for treating neuropathic pain. Perspective: Our study provides evidence suggesting the mechanisms by which KDS, a novel MAO-B inhibitor, can be effective in pain relief. KDS, by targeting multiple mechanisms involved in BDNF/TrkB/NR2B-related excitatory transmission and neuroinflammation, may represent the next future of pain medicine.
Learn More >With the rise in telehealth due to the COVID-19 pandemic, further research is needed to determine how to optimize virtual delivery of existing integrative oncology interventions for cancer treatment-related symptoms. The purpose of this qualitative analysis was to explore cancer survivors' perspectives of the acceptability and satisfaction of an 8-week, virtual yoga intervention for cancer survivors with chronic chemotherapy-induced peripheral neuropathy pain. Fourteen participants with chronic chemotherapy-induced peripheral neuropathy pain who completed the virtual yoga intervention were interviewed using a semistructured interview guide. Themes were derived from the data using inductive content analysis methods. Main findings from the interviews included the following: (1) participants were willing to try new nonpharmacological treatments for chemotherapy-induced peripheral neuropathy due to the high symptom burden and prior lack of success with medications; (2) participants highly rated the flexibility offered by the virtual format, but desired the social support potentially offered by practicing in-person yoga; and (3) the impact of virtual yoga on chemotherapy-induced peripheral neuropathy severity was unclear. There were several barriers to participants' use of virtual yoga for chronic chemotherapy-induced peripheral neuropathy pain (eg, technology, lack of space/equipment). The results may be used to improve the design and delivery of future trials testing virtual yoga for chronic chemotherapy-induced peripheral neuropathy pain.
Learn More >Stigma is defined by the World Health Organization (WHO) as "a mark of shame, disgrace or disapproval that results in an individual being rejected, discriminated against and excluded from participating in a number of different areas of society". Extensive literature searches have documented stigma in the context of health. Among the physical health conditions that are associated with stigma, chronic pain deserves particular attention. Stigma experienced by individuals with chronic pain affects their entire life. Literature identifies multiple dimensions or types of stigma, including public stigma, structural stigma and internalized stigma. Recent literature supports the biopsychosocial model of pain, according to which biological, psychological and sociocultural variables interact in a dynamic manner to shape an individual's response to chronic pain. Chronic pain affects a higher proportion of women than men around the world. There is an inadequate education of health care professionals regarding pain assessment and their insecurity to manage patients with chronic pain. A first-line intervention strategy could be to promote pain education and to expand knowledge and assessment of chronic pain, as recently highlighted for headache disorders, paradigmatically for resistant or refractory migraine, whose diagnosis, without an adequate education to understand the possible fluctuations of the disease, may have profound psychological implications with the idea of insolvability and contribute to stigmatizing the patient.
Learn More >To verify the validity of the proposed pain treatment approach, which is based on concomitant blocking of the Transient Receptor Potential Ankyrin 1 (TRPA1) channel and phosphodiesterases (PDEs) 4B/7A activity, we continued our pharmacological studies on 8-alkoxypurine-2,6-diones selected based on previous in vitro screening.
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