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PubMed2026

Role of OPRM1 A118G polymorphism in tramadol analgesia following third molar surgery: a pharmacogenomic study.

BACKGROUND: The OPRM1 A118G (rs1799971) polymorphism has been implicated in interindividual variability in opioid analgesic response, but its influence on tramadol efficacy remains uncertain. This study evaluated the association between OPRM1 A118G and postoperative analgesic response to tramadol following mandibular third molar surgery. METHODS: In this prospective pharmacogenomic study, 53 adults undergoing impacted mandibular third molar extraction were enrolled. Genomic DNA was analyzed for OPRM1 A118G (rs1799971) using amplification refractory mutation system polymerase chain reaction (ARMS-PCR). All procedures were performed under 2% lignocaine with adrenaline. Tramadol (50 mg) was administered after the onset of postoperative pain. Pain intensity was assessed using the Visual Analogue Scale (VAS) and Short-Form McGill Pain Questionnaire at 2, 4, and 6 hours. The primary outcome was summed pain intensity difference (SPID, 2-6 hours). RESULTS: Genotype frequencies were in Hardy-Weinberg equilibrium. No significant association was observed between OPRM1 genotype and SPID, VAS reduction, Pain Rating Index change, or responder status during the 6-hour observation period (all p > 0.05). CONCLUSION: OPRM1 A118G was not significantly associated with early tramadol analgesic response following third molar surgery. Larger studies incorporating both OPRM1 and CYP2D6 genotyping are needed to clarify the genetic determinants of tramadol analgesia as CYP2D6 gene is required for tramadol metabolism.

OPRM1↗

PubMed2026

Looking to the Future: How Will Personalised Medicine Impact Facial Plastic Surgery.

AIMS AND BACKGROUNDS: The objectives of this study are to examine the emerging role of personalized medicine in facial plastic surgery and to consider how biologically, anatomically, and psychologically tailored approaches may refine both aesthetic and reconstructive care. HISTORICAL ASPECTS: Facial plastic surgery has traditionally relied on anatomical principles, surgical expertise, and population-based evidence. Personalized medicine represents a shift toward more individualized care by incorporating patient-specific biological and phenotypic variation into clinical decision-making. ANATOMY: Facial plastic surgery is uniquely dependent on subtle anatomical variation, soft tissue characteristics, wound healing behavior, and age-related change. These factors differ considerably between individuals and have a direct impact on both surgical planning and outcomes. TECHNOLOGY: Advances in genomics, pharmacogenomics, artificial intelligence, tissue engineering, and three-dimensional modelling are expanding the scope of personalized care. These technologies may improve prediction of healing, treatment response, complication risk, and reconstructive requirements. PATIENT SELECTION: Personalized medicine may support more accurate patient selection by identifying those at increased risk of adverse scarring, variable response to injectables or pharmacotherapy, or differential reconstructive needs, thereby improving counselling and expectation management. TECHNIQUES: Potential applications include tailored incision planning, individualized facial rejuvenation strategies, personalized perioperative pharmacological regimens, and patient-specific reconstructive scaffolds, grafts, and implants. POSTOPERATIVE CARE: Postoperative management may also become more individualized through better prediction of inflammatory response, scar formation, analgesic requirements, and recovery trajectory, allowing more precise surveillance and adjunctive treatment. CURRENT AND FUTURE DEVELOPMENT: Although many applications remain investigational, continued progress in regenerative medicine, molecular profiling, and predictive analytics is likely to accelerate clinical translation. Ethical challenges relating to privacy, bias, and equitable access must, however, remain central. CONCLUSION AND CLINICAL RELEVANCE: Personalized medicine has the potential to enhance precision, safety, and patient-centered care in facial plastic surgery. Its future value will depend on thoughtful integration into practice as an adjunct to, rather than a replacement for, surgical judgement and aesthetic insight.

Journal Article↗

PubMed2024

Associations between (pharmaco-)genetic markers and postoperative pain after inguinal hernia repair - a prospective study protocol.

BACKGROUND: Postoperative pain is a common complication following surgery, with severity and duration varying between patients. Chronic postoperative pain after inguinal hernia surgery has an incidence rate of approximately 10%. Risk factors for acute and chronic pain following hernia surgery include age, sex, psychosocial factors, and demographic background. Additionally, genetic polymorphisms in enzymes involved in pain mechanisms, as well as the metabolism of analgesics might influence pain perception, pain development, and response to pain medications. Key enzymes include the catechol-o-methyltransferase (COMT), the µ-opioid receptor 1 (OPRM1), and the cytochrome P450 2D6 (CYP2D6). CYP2D6 plays a crucial role in metabolizing analgesics such as tramadol, codeine, and oxycodone. It is also suspected to be involved in the synthesis of catecholamines and endogenous morphines suggesting a potential role in pathophysiology of pain. We hypothesize that the CYP2D6 activity influences the development of postoperative pain after hernia surgery. METHODS: This study is a prospective, observational, multicenter association study investigating adult patients scheduled for inguinal hernia surgery using a robotic-assisted (rTAPP) approach. Patients are enrolled during the preoperative surgical consultation. A buccal swab is collected for genetic testing at this time. Pain at the site of the hernia is assessed using the validated EuraHSQoL score preoperatively and at 2, 4, and 6 weeks postoperatively. Additionally, information on co-medication and details of the surgery will be collected. The planned number of participants is 350 patients. The primary objective is to analyze the association between different genotype-predicted CYP2D6 phenotypes and patient-reported pain intensity 6 weeks after surgery. Secondary objectives include the association between further genetic variants, such as the COMT rs4680 and OPRM1 rs1799971 genotype, and pain severity. Additionally, the potential of pharmacogenetic panel testing to optimize analgesic therapy in hernia surgery patients will be explored. DISCUSSION: The findings of this study are expected to provide valuable insights into identifying patients at higher risk for postoperative pain before surgery. This knowledge could pave the way for tailored interventions during and after surgery for these specific patients. TRIAL REGISTRATION: Deutsches Register Klinischer Studien https://www.drks.de/DRKS00034796 Registered on August 07, 2024.

Genetic Association Studies↗

PubMed2026

Microglial modulation in general anesthesia: molecular.

General anesthetics profoundly alter brain function and consciousness, yet the mechanisms underlying these effects remain incompletely understood. Although traditional studies have primarily focused on neuronal targets, accumulating evidence suggests that microglia dynamically respond to anesthetic exposure and may participate in anesthesia-associated neurophysiological changes. Beyond their established immune functions, microglia are increasingly implicated in synaptic remodeling, metabolic regulation, neuronal activity surveillance, and neuron-glia communication. Recent studies indicate that different classes of anesthetic agents modulate microglial activity through diverse and context-dependent mechanisms involving inflammatory signaling, purinergic pathways, calcium dynamics, mitochondrial metabolism, and neural circuit interactions. These responses are associated with postoperative neurocognitive disorders, altered synaptic plasticity, and anesthesia-related changes in brain states. In this review, we summarize current evidence regarding the effects of volatile anesthetics, intravenous anesthetics, and analgesics on microglial function and discuss the molecular, functional, and circuit-level mechanisms underlying anesthesia-associated neuron-microglia interactions. We further highlight the dynamic and heterogeneous nature of microglial responses during anesthesia and discuss current limitations in the field, including the lack of temporally resolved and cell-specific approaches. Understanding these processes may provide insights into anesthesia-associated neurocognitive dysfunction and support the development of neuroimmune-targeted strategies in anesthesiology.

General anesthesia↗

PubMed2026

40 Hz light flickering alleviates chronic pain via adenosine signaling in the retina-amygdala pathway.

Chronic pain affects over 20% of the global population, yet frontline treatments remain limited in efficacy and are often hampered by serious side effects. In search of novel and effective neuromodulation alternatives, we discovered that 40 Hz flickering light effectively alleviates inflammatory and neuropathic pain in mice. We identified the retina-central amygdala (CeA) pathway as a critical conduit for the analgesic effects of 40 Hz flickering light. Using circuit-specific manipulations, we demonstrated that activation of the retina-CeA pathway is both sufficient to mimic and necessary to mediate the analgesic outcomes of 40 Hz light stimulation. In terms of mechanism, we found that 40 Hz light flickering significantly increases extracellular adenosine levels in the CeA. Local pharmacological blockade of equilibrative nucleoside transporters prevented this adenosine increase and abolished the analgesic effects of 40 Hz light flickering, whereas focal adenosine infusion phenocopied the light-induced analgesia. Both interventions required A2A receptor signaling to suppress nociceptive responses. Furthermore, we found that hyperalgesia could be destabilized in the CeA and reversed by 40 Hz light stimulation or adenosine infusion, mirroring memory reconsolidation processes and implicating the CeA as a key locus for pain memory erasure. Collectively, our findings demonstrate the multifaceted therapeutic benefits of 40 Hz light flickering as a novel non-invasive approach for pain management and reveal a distinct retina-CeA circuit and adenosine signaling mechanism for control of chronic pain and pain memory.

Animals↗

PubMed2026

Inflammatory Serum Olink Proteomics in Cancer-Related Pain Treated with Opioids: A Pilot Cross-Sectional and Longitudinal Study.

Opioid analgesia shows substantial interindividual variability in cancer patients, yet the underlying serum inflammatory alterations remain poorly characterized. This study collected plasma samples from 44 cancer pain patients before and after opioid initiation, quantifying 92 immunoinflammation proteins by Olink proteomics. Cross-sectional analysis identified nine differentially expressed proteins between responders and nonresponders. A five-protein nomogram involving TGF-α, EN-RAGE, CASP-8, ST1A1, and IL-10RA demonstrated superior predictive performance for opioid efficacy (AUC 0.902) compared to traditional CRP (AUC 0.625). Longitudinal analysis of this population revealed upregulation of β-NGF, MCP-4, IL-1alpha, and IL-13, and downregulation of CD6, IL-12beta, and SCF after treatment. STRING analysis clustered these proteins into three functional groups: efficacy-related (NGF), bowel-inflammation-related (IL-12/IL-13), and CD6-related. Notably, expression of IL-12β showed a significant efficacy-constipation interaction: constipation completely reversed the efficacy-IL-12 association, and higher IL-12 levels predicted favorable response only in nonconstipated patients. These findings established a pretreatment protein signature for predicting opioid efficacy and revealed systemic immune reprogramming following opioid therapy.

Humans↗

PubMed2026

Evaluation of the intraoperative analgesic effects of perioperative electroacupuncture: a randomised, blinded clinical trial in dogs.

OBJECTIVE: To evaluate the effect of perioperative electroacupuncture (EA) on intraoperative analgesic requirements in dogs undergoing tibial tuberosity advancement (TTA) surgery. STUDY DESIGN: Prospective, randomised, blinded, controlled clinical study. ANIMALS: A group of 29 client-owned dogs diagnosed with cranial cruciate ligament rupture that underwent TTA surgery. METHODS: Dogs were treated with EA at predefined acupuncture points (LI-4, ST-36, LIV-3, SP-6 and GB-34) perioperatively as additional analgesia (group EA, n = 14) or were allocated to the control group (group C, n = 15). All dogs were anaesthetised with a standardised protocol including methadone, dexmedetomidine, propofol and ketamine. The intraoperative delivery of sevoflurane and fentanyl was guided in response to signs of nociception by a purpose-designed flowchart, by the same anaesthetist who was blinded to treatment group. A Wilcoxon rank sum test was applied for the fentanyl consumption analysis. Heart rate, mean arterial blood pressure and end-tidal sevoflurane were descriptively analysed between groups for specific time points. A p value < 0.05 was considered significant. RESULTS: The EA group needed significantly less fentanyl with 0.7 (0-2.7) μg kg-1 hour-1 administered versus 2.0 (1.2-5.5) μg kg-1 hour-1 in group C (p = 0.031). Fifty percent of the EA group was not administered a fentanyl bolus, whereas all dogs in group C required at least one bolus. CONCLUSIONS AND CLINICAL RELEVANCE: Perioperative EA reduced mean fentanyl consumption by more than 60% in dogs undergoing TTA surgery.

Animals↗

PubMed2026

Continuous Intravenous Lidocaine for Refractory Cancer Pain in Palliative Care: A Multicenter Feasibility Study.

ObjectivesTo assess the feasibility and tolerability of continuous low-dose intravenous lidocaine infusion in patients with opioid-refractory cancer pain receiving palliative care, and to explore its potential impact on pain outcomes in real-world clinical conditions.MethodsWe conducted a multicenter, randomized, double-blind, placebo-controlled feasibility study in palliative care units to evaluate continuous intravenous lidocaine infusion in patients with opioid-refractory cancer pain. Patients were randomized to receive lidocaine (5 mg/kg/day, increased to 8 mg/kg/day if pain reduction was <30% after 24 h) or placebo for 48 h. Pain intensity was assessed using the Numeric Pain Intensity Scale, with a clinically meaningful response defined as a ≥30% reduction from baseline at 40 min. Secondary outcomes included pain evolution over time, neuropathic pain, symptom burden, and tolerability.ResultsThirty-five patients were included in the final analysis (18 lidocaine, 17 placebo). No significant difference was observed between lidocaine and placebo for the primary endpoint or for secondary pain outcomes. Reductions in pain intensity were observed in both groups. In the lidocaine group, 61% of patients required dose escalation to 8 mg/kg/day. Continuous intravenous lidocaine infusion was generally well tolerated, with mostly mild adverse events and no unexpected toxicity.ConclusionIn this multicenter feasibility study, continuous low-dose intravenous lidocaine did not demonstrate a clinically meaningful analgesic benefit over placebo. As the planned sample size was not reached, the study was underpowered. These findings highlight the challenges of randomized trials in palliative care and may inform future feasibility-oriented designs.

Humans↗

PubMed2025

The hedonic impact of cleaner-client fish interactions is mediated by the opioid system.

According to the 'incentive salience hypothesis' reward processing involves two main components, including the motivation to obtain a reward (i.e. incentive salience or 'wanting') and the hedonic pleasure felt during its consumption (i.e. hedonic impact or 'liking'), which are dissociable. The processing of these hedonic mechanisms is suggested to be mediated by opioid neurotransmission; however, most evidence comes from humans and other mammals. Here we argue that, in mutualistic associations, client fish seek to interact with cleaner fish not only due to the immediate benefits of being cleaned but also because of the hedonic impact of tactile stimulation, modulated by the opioid system. We used a conditioned place preference (CPP) paradigm to test the hedonic dimension of motivation to be cleaned and found that de-parasitized client fish (the butterflyfish Chaetodon auriga) preferred the compartment paired with cleaner fish (Labroides dimidiatus). Treatment with the μ-opioid receptor agonist The µ-opioid receptor agonist 2-Ala-4-mephe-5-gly-enkephalin (DAMGO) dose-dependently increased preference, while treatment with the antagonist naloxone decreased it. To test for fish incentive salience, we used a detour task, with barriers being added after each trial to demand higher response strength to reach the target and found that client fish can circumvent barriers to reach a cleaner-adjacent compartment. Response strength (number of barriers added before 'giving up') was not affected by treatment with either naloxone or DAMGO. Our results show that cleaner-client interactions are hedonically positive for clients, an effect that is mediated by the opiodergic system. Visual contact with cleaners is sufficient to activate incentive salience programmes, but no evidence of participation of the opioidergic system in these programmes was found. Overall, we provide the first evidence confirming the participation of the opioidergic system in motivation to be cleaned in mutualistic associations.

Animals↗

PubMed2026

Unraveling the Mystery of Pain: A Unique Clinical Encounter and Case Report.

BACKGROUND: The Clinical Pharmacogenetics Implementation Consortium published an updated guideline for opioids and CYP2D6, OPRM1, and COMT in December 2020. These guidelines include recommendations to avoid key opioids in patients who are ultrarapid or poor metabolizers of CYP2D6 to avoid toxicity and optimize efficacy. CASE REPORT: An older woman encountered a letter to the editor in a family magazine regarding genomically based responses to opioids. She reached out for more information and assistance, attesting to continued lack of analgesia to opioids prescribed during occasions of severe pain over the course of many years. A pharmacogenomic analysis proved to be the key to solving her mystery. CONCLUSION: Pharmacogenomic results may provide life-altering information transforming a patient's perspective on health care. Personalized medicine may be a key component in providing objective evidence for opioid treatment efficacy. There is a critical need for both provider and patient education to increase awareness of pharmacogenomics and how it can be applied to effective pharmacotherapy. Research is needed to explore appropriate, effective educational methods.

Humans↗

PubMed2026

Thoracic paravertebral block with different doses of liposomal bupivacaine versus ropivacaine for postoperative analgesia in single-port thoracoscopic lung surgery: a randomized clinical trial.

OBJECTIVE: To evaluate the analgesic efficacy of thoracic paravertebral block (TPVB) with different doses of liposomal bupivacaine (LB) or ropivacaine in patients undergoing single-port thoracoscopic lung surgery. METHODS: A total of 105 patients scheduled for video-assisted single-port thoracoscopic lung surgery were randomized in a 1:1:1 ratio into three groups: low-dose LB group (group LL), high-dose LB group (group HL), or ropivacaine group (group R). All received ultrasound-guided TPVB at the T5/6 level preoperatively. The primary outcome was the area under the curve (AUC) of NRS of pain at activity (AUC-aNRS) from 1 to 72 h postoperatively. Secondary outcomes included the AUC of NRS of pain at rest (AUC-rNRS) from 1 to 72 h postoperatively, NRS of pain at rest and at activity at 1, 6, 24, 48, and 72 h postoperatively, and the cumulative opioid consumption at 24, 48, and 72 h postoperatively. Additionally, postoperative recovery and adverse events were assessed. RESULTS: AUC-aNRS differed significantly among groups (p = 0.0092), with high-dose LB lower than low-dose LB (p = 0.0071), but not versus ropivacaine. No significant difference was found in AUC-rNRS (p > 0.05). The group-by-time interactions for NRS of pain at rest and at activity were not significant (p > 0.05). Cumulative opioid consumption at 24, 48, and 72 h was lower in group HL versus group LL (all p < 0.017), but not versus ropivacaine. Postoperative recovery and adverse events showed no differences (p > 0.05). CONCLUSION: LB combined with TPVB is not superior to ropivacaine for postoperative analgesia in single-port thoracoscopic lung resection.

Humans↗