@qspainrelief.bsky.social
QSPainRelief is an EU-funded research project for #ChronicPain patients. We use a translational quantitative systems #pharmacology (#QSP) approach and computer models to identify the best combinatorial #PainRelief treatments. 🌐 https://qspainrelief.eu
✨Final spotlight of this series: Our open access protocol on a self-medication #MouseModel of #ChronicPain that helps assess spontaneous #PainRelief & #DrugAbuse liability
🔗 doi.org/10.21769/Bio...
Cabañero et al. (2022), co-authored by Beltrán Álvarez & Rafael Maldonado
#Neuroscience #Analgesics
5️⃣ García-Blanco et al. (2002): www.jci.org/articles/vie...
📖 miRNA signatures associated with vulnerability to food addiction in mice & humans
💡Common #miRNA #signatures in mice & humans may underlie vulnerability to #FoodAddiction.
💡Targeting those miRNAs may modify maladaptive eating phenotypes.
4️⃣ academic.oup.com/ismej/articl...
📖 Presence of #Blastocystis in #GutMicrobiota associated with decreased executive function
💡Blastocystis colonisation in the gut is associated with measurable deficits in executive #CognitiveFunction, suggesting a possible #GutBrainAxis influence on cognition.
3️⃣ doi.org/10.3389/fpsy...
📖 Tetrahydrocannabinol #THC exposure in #adolescence elevates #impulsivity-like behaviour in #adulthood in a self-administration mouse model
💡Young-age THC exposure may produce a lasting impulsivity increase & neurochemical changes that predispose to #AddictiveBehaviour.
2️⃣García-Blanco et al., 2023 www.sciencedirect.com/science/arti...
📖 #CB2 #CannabinoidReceptor & the development of food addiction in mice
💡CB2R is a modulatory node in the control of hedonic feeding and vulnerability to #FoodAddiction, making it a potential therapeutic target for eating disorders
1️⃣ Del Mar Cajiao-Manrique, Maldonado & Martín-García (2023) doi.org/10.3389/fpha...
📖 A self-administration mouse model to study #CannabinoidAddiction
💡This novel #MouseModel provides a rigorous tool to study #CannabinoidAddiction & the neurobiological mechanisms of #vulnerability vs. #resilience.
🧬🐭👩🦰👨🦰 Translational research - from mice to humans - was central to #QSPainRelief: For better #PainRelief, safer #PainMedication and improved #ChronicPain treatment.
✅ Less pain
😵💫 Fewer side effects
☺️ Better QoL
✨ Here are 5 key papers about 🧠-mechanisms linked to #addiction #cognition #impulsivity
A more #PainRelief-relevant follow-up of the 2020 Sci. Rep. paper is this article by Ricarte, Dalton & Giraldo (2021), a year later:
🔗 doi.org/10.1021/acs....
🧬 Structural assessment of #agonist #efficacy at the μ-opioid receptor #MOR
👉 #morphine and #fentanyl elicit different activation patterns
🔬 Wanna know the P-values for #agonist-dependent #GPCR activation?
👏 One of our 2 high-impact Nature publications was also the 1st QSPainRelief article:
📈 Bruzzese, Dalton & Giraldo (2020) present their #MolecularDynamics work & the best statistics to analyse it.
🔗 www.nature.com/articles/s41...
Here's another important QSPainRelief publication about allosteric sites at #GPCRs: They can be identified by looking at how strongly certain receptor sites are coupled to #conformational changes that occur during activation.
🔗 doi.org/10.3390/ijms...
#allostery #pharmacology #receptors #ligands
Speaking of #allostery: What happens when you mutate the #CannabinoidReceptor (CB1) in silico with a single-point mutation?
Find out👉: doi.org/10.1021/acso...
Spoiler😉: The F237L mutation mimics #allosteric #ligand effects, globally altering #receptor conformations and hindering activation
#GPCR
🎯Feature Alert 🚨
This paper delves into how #BindingKinetics reshape our understanding of #allosteric modulation. When it comes to cooperativity effects, it's all about
👉 WHERE molecules bind
👉 HOW FAST
👉 and in WHICH SEQUENCE
🔗 doi.org/10.1016/j.dr...
#allostery #pharmacology #DrugDesign #GPCRs
🚀 Time-dependent #ligand-receptor #BindingKinetics and functionality in a #heterodimeric receptor model by Ortiz et al. (2024): Predicting how 2 drugs bind to a receptor complex over time - with implications for combination-therapies and #DrugDesign💊
🔗 doi.org/10.1016/j.bc...
#Pharmacology #GPCRs
🔦 Spotlight on link.springer.com/article/10.1...
🧠 Using the LeiCNS-PK3.0 PBPK model, they predicted mouse #brainECF #pharmacokinetics for 10 drugs
✅ Accurate for 7 drugs
✅ First mechanistic #CNS PBPK #model in mice
✅ Strong translational potential
#TranslationalPharmacology #DrugDevelopment
The paper by Budda et al. (2024) relates to the earlier publication by Gülave et al. (2023): doi.org/10.1016/j.ej...
🧠The transport of #morphine across the #BBB is non-linear - this is important for #receptor #occupancy predictions. Find out how BBB dynamics inform smarter, safer dosing strategies!
🧠 Non-linear blood-brain barrier #BBB transport & dosing influence #receptor #occupancy ratios of #morphine and #MorphineMetabolites (M3G + M6G) in the #pain matrix.
💡This might also explain some inter-individual differences!
🔗 bpspubs.onlinelibrary.wiley.com/doi/10.1111/...
#ChronicPain #opioids
We have exceptional treatments for RMDs but that doesn't always mean the chronic pain is treated. We need to be open to pain specialists. Patients need to keep advocating for themselves when still in pain despite their RMD appearing under control. Nadia Malliou at #eular2025 @eular.org
🔬By Bertayli et al (2024): PK-PD modelling of #morphine, #pregabalin & their combination shows synergistic #analgesia.
Potential impact:
👉 Lowering #opioid doses
👉 Maintaining treatment efficacy
👉 Reducing side effects & abuse liability
🔗 www.page-meeting.org/default.asp?...
#ChronicPain #Pain
📖 Just published 💊
👉 Introducing a rigorous theoretical framework for better #quantification of #drug-target #ResidenceTime (RT) - a key metric in #BindingKinetics that has lacked a firm quantitative foundation to date 👏
🔗 www.sciencedirect.com/science/arti...
#Pharmacology #ComputationalBiology
🧪 Our new paper on the #pharmacokinetics of P-glycoprotein substrates in #brainECF shows how #invitro transport data can guide #invivo 🧠🐭🚶♀️predictions, but that high variability still limits the robustness of these predictions.
🔗 link.springer.com/article/10.1...
👉LeiCNS-PK3.4 PBPK model #CNS #brain
🫶 Our recent review shows that #SocialSupport is a powerful boost for #MentalHealth in #ChronicPain ⚡ , but its impact on pain intensity and daily function is less clear.
👉 Social support is crucial, but HOW matters
🔗 doi.org/10.1371/jour...
#QoL #PainResearch #Pain
@plosone.org @efic.bsky.social
🧠 Predicting how well #drug molecules cross the blood-brain barrier: Gülave et al. built a #MachineLearning model for the unbound brain-to-plasma partition coefficient (98 compounds).
link.springer.com/article/10.1...
👉Best algorithm: Random Forest
💡Great for #CNS drug discovery!
#BBB #PBPK #ML
💊 Morphine is a P-glycoprotein substrate, but do P-gp inhibitors meaningfully change #CNS exposure?
🧠 Likely not: A physiology-based pharmacokinetic #PBPK model predicts negligible impact across populations.
#BBB #DrugInteractions #morphine #modelling #brain
🔗 link.springer.com/article/10.1...
Preoperative #susceptibility to secondary #hyperalgesia is associated with cough-evoked #pain 2 months after #thoracotomy (Gousset et al., 2025)
👉 onlinelibrary.wiley.com/doi/10.1002/...
⚕️Patients with high secondary hyperalgesia pre-op had more cough-evoked pain 2 months later.
#PainPrediction
🧠 Central sensitisation drives #ChronicPain.
This PhD thesis by Solenn Gousset (2025) bridges experimental pain models and clinical perspectives, exploring methods to measure and predict #CentralSensitisation.
👉 Explore the mechanisms behind persistent pain!
🔗 dial.uclouvain.be/pr/boreal/ob...
🧠 Ever wondered what affects how #morphine works in the brain? This modelling study found #beta-endorphin to be a major player in how morphine occupies its µ-opioid receptors (MORs) in rat #hypothalamus 🐭
#EndogenousOpioids matter, folks!
#BindingKinetics #MOR
www.sciencedirect.com/science/arti...
💡What happens when you combine 2 analgesics?
🔬 Bakker et al. (2025) used a nociceptive test battery to investigate #morphine + #pregabalin. Result: Increased #PainTolerance, only minimal side effects. A promising step toward safer #PainRelief & lower #opioid doses.
pubs.acs.org/doi/10.1021/...
20% live with #ChronicPain - many without effective treatment
The QSPainRelief database uses published data, existing meds & advanced models to help design more effective therapies
🎥 Intro video: youtu.be/0VWoc2fqks8
🔗 Database: qspainrelief.lacdr.leidenuniv.nl
#PainRelief #PersonalisedMedicine
🎓 Dive into the complexity of #OpioidReceptors with Prof. Andrea Bedini (from @unibo.it) in his insightful Masterclass.
👉 A must-watch for anyone interested in #MOR, #KOR, and chronic pain therapeutics!
▶️ youtu.be/dcGBm03nvhI
#GPCR #ChronicPain #Pharmacology
@iasp.bsky.social
@efic.bsky.social
