1 6805 105 [EPIGENETICS : IMPORTANT ASPECTS FOR ANESTHESIOLOGISTS, PAIN AND INTENSIVE CARE PHYSICIANS]. EPIGENETICS, I.E. AN ALTERED READING OF THE GENOME WITHOUT ALTERING THE GENES THEMSELVES IS A GROWING SCIENTIFIC FIELD. A DISTINCTION IS MADE BETWEEN CHANGES IN THE DNA BY MODIFICATION OF THE HISTONES AND NON-CODING RNA THAT ALTER THE MESSENGER (M)RNAS. EPIGENETIC MODIFICATIONS CAN BE TRIGGERED BY PERSONAL CIRCUMSTANCES OR OTHER EXTERNAL FACTORS AND THEREFORE INFLUENCE THE OCCURRENCE OF DISEASES. EPIGENETICS ARE THEREFORE OF PARTICULAR INTEREST TO ANESTHESIOLOGISTS, PAIN SPECIALISTS AND INTENSIVE CARE PHYSICIANS, AS ANESTHETIC DRUGS MAY HAVE A LONG-TERM INFLUENCE ON PROTEIN TRANSCRIPTION LEADING FOR EXAMPLE TO ALTERATIONS IN NEUROCOGNITION AFTER ANESTHESIA, CHRONIFICATION OF POSTOPERATIVE PAIN AND IMMUNE RESPONSE IN SEPSIS. NON-CODING MICRORNAS KNOWN TO BE ALTERED IN A VARIETY OF PERIOPERATIVELY RELEVANT DISEASES E. G. HEART INFARCT, MIGHT SERVE AS PROGNOSTIC FACTORS OF PERIOPERATIVE OUTCOME. MOREOVER, THERE ARE WAYS TO INFLUENCE EPIGENETIC CHANGES THROUGH LIFE STYLE AND CERTAIN MEDICATIONS. IN THIS REVIEW ARTICLE, EXAMPLES OF ANESTHESIA, INTENSIVE CARE AND PAIN MEDICINE-RELEVANT DISEASES AND THE INFLUENCE OF EPIGENETICS ON THEM ARE PRESENTED. 2018 2 5839 26 STROKE RECOVERY ENHANCING THERAPIES: LESSONS FROM RECENT CLINICAL TRIALS. POSTSTROKE RECOVERY PROCESSES INCLUDE RESTORATION OR COMPENSATION OF FUNCTION, RESPECTIVELY FUNCTIONS INITIALLY LOST OR NEW FUNCTIONS ACQUIRED AFTER AN INJURY. THERAPEUTIC INTERVENTIONS CAN ENHANCE THESE PROCESSES AND/OR REDUCE PROCESSES IMPEDING REGENERATION. NUMEROUS EXPERIMENTAL STUDIES SUGGEST GREAT OPPORTUNITIES FOR SUCH TREATMENTS, BUT THE RESULTS FROM RECENT LARGE CLINICAL TRIALS USING NEUROMODULATORS SUCH AS DOPAMINE AND FLUOXETINE ARE DISAPPOINTING. THE REASONS FOR THIS ARE MANIFOLD AFFECTING FORWARD TRANSLATION OF RESULTS FROM ANIMALS MODELS INTO THE HUMAN SITUATION. THIS "TRANSLATIONAL ROAD BLOCK" IS DEFINED BY DIFFERENCES BETWEEN ANIMALS AND HUMANS WITH REGARD TO THE GENETIC AND EPIGENETIC BACKGROUND, SIZE AND ANATOMY OF THE BRAIN, CEREBRAL VASCULAR ANATOMY, IMMUNE SYSTEM, AS WELL AS CLINICAL FUNCTION AND BEHAVIOR. BACKWARD BLOCKADE INCLUDES THE INCOMPATIBLE ADAPTION OF TARGETS AND OUTCOMES IN CLINICAL TRIALS WITH REGARD TO PRIOR PRECLINICAL FINDINGS. FOR EXAMPLE, THE DESIGN OF CLINICAL RECOVERY TRIALS VARIES WIDELY AND WAS CHARACTERIZED BY THE SELECTION OF DIFFERENT CLINICAL ENDPOINTS, THE INCLUSION A BROAD SPECTRUM OF STROKE SUBTYPES AND CLINICAL SYNDROMES AS WELL AS DIFFERENT TIME WINDOWS FOR TREATMENT INITIATION AFTER INFARCT ONSET. THIS REVIEW WILL DISCUSS THESE ASPECTS BASED ON THE RESULTS OF THE RECENT STROKE RECOVERY TRIALS WITH THE GOAL TO CONTRIBUTE TO THE CURRENTLY BIGGEST UNMET NEED IN STROKE RESEARCH - THE DEVELOPMENT OF A RECOVERY ENHANCING THERAPY THAT IMPROVES THE FUNCTIONAL OUTCOME OF A CHRONIC STROKE PATIENT. 2022 3 257 33 ADVANCES IN ONCOANAESTHESIA AND CANCER PAIN. INTRODUCTION: THE GROWING INTEREST ON HOW PERI-?OPERATIVE INTERVENTIONS, ESPECIALLY REGIONAL ANESTHESIA, DURING CANCER SURGERY CAN ALTER ONCOLOGICAL OUTCOME INCREASING DISEASE FREE SURVIVAL IS PROBABLY RESPONSIBLE FOR THE BIRTH OF THE NEW SUBSPECIALTY CALLED ONCO-ANESTHESIA. A PARADIGM SHIFT IN THE CONCEPT OF ANESTHETIC MANAGEMENT HAS OCCURRED RECENTLY OWING TO THE INNUMERABLE DIVERSE REVELATIONS FROM THE ONGOING RESEARCH IN THIS FIELD. DISCUSSION: LONG LASTING BUT REVERSIBLE EPIGENETIC CHANGES CAN OCCUR DUE TO SURGICAL STRESS AND PERIOPERATIVE ANESTHETIC MEDICATIONS. THE EXACT RELATIONSHIP BETWEEN THESE FACTORS AND TUMOR BIOLOGY IS BEING STUDIED FURTHER. A POPULAR TOPIC UNDER RESEARCH NOW IS THE INFLUENCE OF REGIONAL ANESTHESIA ON CANCER RECURRENCE. COMBINING NERVE BLOCKS WITH TOTAL INTRAVENOUS ANESTHESIA (TIVA) BRINGS DOWN THE REQUIREMENT OF OPIOIDS AND VOLATILE ANESTHETIC AGENTS IMPLICATED IN CANCER RECURRENCE. THE STUDY OF MECHANISM OF PAIN AT THE MOLECULAR LEVEL HAS LED TO THE DISCOVERY OF NOVEL MODES OF PREVENTION OF CHRONIC POST-SURGICAL PAIN. NEWER COMBINATION AGGRESSIVE TREATMENT THERAPIES -INTRAOPERATIVE CHEMOTHERAPY AND RADIOTHERAPY, ISOLATED LIMB PERFUSION, PHOTODYNAMIC THERAPY AND ROBOTIC SURGERY REQUIRE SPECIALIZED ANESTHETIC MANAGEMENT. THE COVID PANDEMIC INTRODUCED NEW GUIDELINES FOR SAFE MANAGEMENT OF ONCOSURGICAL PATIENTS .USE OF GENOMIC MAPPING TO PERSONALIZE PAIN MANAGEMENT WILL BE THE BREAKTHROUGH OF THE DECADE. CONCLUSION: THE DISCOVERY THAT ANESTHETIC STRATEGY COULD HAVE SIGNIFICANT ONCOLOGICAL SEQUEL IS A QUANTUM LEAP FORWARD. AVOIDING SOME ANESTHETIC MEDICATIONS MAY DECREASE CANCER RECURRENCE. COMPREHENSIVE CANCER CARE AND TRANSLATIONAL RESEARCH WILL PAVE THE WAY TO UNCOVER SAFE ANESTHETIC PRACTICES. 2021 4 3010 27 GENETICS AND EPIGENETICS IN PERIOPERATIVE MEDICINE. PURPOSE OF REVIEW: TO SUMMARIZE IS TO REVIEW RECENT PROGRESS IN 'GENOMIC' SCIENCE AND HOW THIS MAY BE APPLIED TO THE PERIOPERATIVE ENVIRONMENT. ALTHOUGH INVESTIGATIONS THAT RELATE GENETIC VARIATION TO PERIOPERATIVE OUTCOMES CONTINUE, IT IS INCREASINGLY APPARENT THAT EPIGENETIC MECHANISMS MAY CONTRIBUTE TO MUCH OF THE OBSERVED VARIATION IN COMPLEX OUTCOMES NOT OTHERWISE EXPLAINED BY DIFFERENCES IN GENETIC SEQUENCE. RECENT FINDINGS: EXAMPLES OF RECENT FINDINGS RELATING TO THE ROLE OF EPIGENETIC MODIFICATIONS IN COMPLEX DISEASE AND OUTCOMES ARE DERIVED FROM RESEARCH INTO TYPE 1 DIABETES, PAIN, AND THE HYPOXIC RESPONSE. THESE STUDIES PROVIDE MODELS FOR FUTURE COHORT STUDY DESIGN, POTENTIAL PERIOPERATIVE DRUG TARGETS, AND HYPOTHESIS DEVELOPMENT. GENETIC AND EPIGENETIC FACTORS COMBINE TO ALTER BOTH GENE EXPRESSION AND DRUG RESPONSES AT BOTH PHARMACOKINETIC AND PHARMACODYNAMIC LEVELS. THESE FACTORS IMPACT ON THE EFFICACY AND SAFETY OF MULTIPLE DRUG CLASSES USED IN PERIOPERATIVE MEDICINE. SUMMARY: ENHANCING OUR UNDERSTANDING OF THE WAY IN WHICH PATIENTS AS GENOMIC ORGANISMS INTERACT WITH THE PERIOPERATIVE ENVIRONMENT REQUIRES A MORE SOPHISTICATED APPRECIATION OF THE FACTORS GOVERNING GENE EXPRESSION THAN HAS BEEN THE CASE TO DATE. EPIGENETIC MECHANISMS ARE SURE TO PLAY A PIVOTAL ROLE IN WHAT IS ESSENTIALLY AN ACQUIRED PHENOTYPE. 2012 5 4532 31 MULTIMODAL ANALGESIA FOR PERIOPERATIVE MANAGEMENT OF PATIENTS PRESENTING FOR SPINAL SURGERY. MULTIMODAL, NON-OPIOID BASED ANALGESIA HAS BECOME THE CORNERSTONE OF ERAS PROTOCOLS FOR EFFECTIVE ANALGESIA AFTER SPINAL SURGERY. OPIOID SIDE EFFECTS, DEPENDENCE AND LEGISLATION RESTRICTING LONG TERM OPIOID USE HAS LED TO A RESURGENCE IN INTEREST IN OPIOID SPARING TECHNIQUES. THE INCREASING ARRAY OF MULTIMODAL OPIOID SPARING ANALGESICS AVAILABLE FOR SPINAL SURGERY TARGETING NOVEL RECEPTORS, TRANSMITTERS, AND ALTERING EPIGENETICS CAN HELP PROVIDE AN OPTIMAL PERIOPERATIVE EXPERIENCE WITH LESS OPIOID SIDE EFFECTS AND LONG-TERM DEPENDENCE. EPIGENETIC MECHANISMS OF PAIN MAY ENHANCE OR SUPPRESS GENE EXPRESSION, WITHOUT ALTERING THE GENOME ITSELF. SUCH MECHANISMS ARE COMPLEX, DYNAMIC AND RESPONSIVE TO ENVIRONMENT. ALTERATIONS THAT OCCUR CAN AFFECT THE PATHOPHYSIOLOGY OF PAIN MANAGEMENT AT A DNA LEVEL, MODIFYING PERCEIVED PAIN RELIEF. IN THIS REVIEW, WE PROVIDE A BRIEF OVERVIEW OF EPIGENETICS OF PAIN, SYSTEMIC LOCAL ANESTHETICS AND NEURAXIAL TECHNIQUES THAT CONTINUE TO REMAIN USEFUL FOR SPINAL SURGERY, NEUROPATHIC AGENTS, AS WELL AS OTHER COMMON AND LESS COMMON TARGET RECEPTORS FOR A TRULY MULTIMODAL APPROACH TO PERIOPERATIVE PAIN MANAGEMENT. 2019 6 4608 28 NEONATAL ANESTHESIA AND DYSREGULATION OF THE EPIGENOMEDAGGER. EACH YEAR, MILLIONS OF INFANTS AND CHILDREN ARE ANESTHETIZED FOR MEDICAL AND SURGICAL PROCEDURES. YET, A SUBSTANTIAL BODY OF PRECLINICAL EVIDENCE SUGGESTS THAT ANESTHETICS ARE NEUROTOXINS THAT CAUSE RAPID AND WIDESPREAD APOPTOTIC CELL DEATH IN THE BRAINS OF INFANT RODENTS AND NONHUMAN PRIMATES. THESE ANIMALS HAVE PERSISTENT IMPAIRMENTS IN COGNITION AND BEHAVIOR MANY WEEKS OR MONTHS AFTER ANESTHESIA EXPOSURE, LEADING US TO HYPOTHESIZE THAT ANESTHETICS DO MORE THAN SIMPLY KILL BRAIN CELLS. INDEED, ANESTHETICS CAUSE CHRONIC NEUROPATHOLOGY IN NEURONS THAT SURVIVE THE INSULT, WHICH THEN INTERFERES WITH MAJOR ASPECTS OF BRAIN DEVELOPMENT, SYNAPTIC PLASTICITY, AND NEURONAL FUNCTION. UNDERSTANDING THE PHENOMENON OF ANESTHESIA-INDUCED DEVELOPMENTAL NEUROTOXICITY IS OF CRITICAL PUBLIC HEALTH IMPORTANCE BECAUSE CLINICAL STUDIES NOW REPORT THAT ANESTHESIA IN HUMAN INFANCY IS ASSOCIATED WITH COGNITIVE AND BEHAVIORAL DEFICITS. IN OUR SEARCH FOR MECHANISTIC EXPLANATIONS FOR WHY A YOUNG AND PLIABLE BRAIN CANNOT FULLY RECOVER FROM A RELATIVELY BRIEF PERIOD OF ANESTHESIA, WE HAVE ACCUMULATED EVIDENCE THAT NEONATAL ANESTHESIA CAN DYSREGULATE EPIGENETIC TAGS THAT INFLUENCE GENE TRANSCRIPTION SUCH AS HISTONE ACETYLATION AND DNA METHYLATION. IN THIS REVIEW, WE BRIEFLY SUMMARIZE THE PHENOMENON OF ANESTHESIA-INDUCED DEVELOPMENTAL NEUROTOXICITY. WE THEN DISCUSS CHRONIC NEUROPATHOLOGY CAUSED BY NEONATAL ANESTHESIA, INCLUDING DISTURBANCES IN COGNITION, SOCIO-AFFECTIVE BEHAVIOR, NEURONAL MORPHOLOGY, AND SYNAPTIC PLASTICITY. FINALLY, WE PRESENT EVIDENCE OF ANESTHESIA-INDUCED GENETIC AND EPIGENETIC DYSREGULATION WITHIN THE DEVELOPING BRAIN THAT MAY BE TRANSMITTED INTERGENERATIONALLY TO ANESTHESIA-NAIVE OFFSPRING. 2021 7 1256 25 CURRENT STUDIES AND FUTURE DIRECTIONS FOR MEDULLOBLASTOMA: A REVIEW FROM THE PACIFIC PEDIATRIC NEURO-ONCOLOGY CONSORTIUM (PNOC) DISEASE WORKING GROUP. MEDULLOBLASTOMA (MB) IS THE MOST COMMON MALIGNANT CENTRAL NERVOUS SYSTEM TUMOR OF CHILDHOOD, COMPRISING A HETEROGENOUS GROUP OF TUMORS EACH WITH DISTINCT BIOLOGY, CLINICAL BEHAVIOR, AND PROGNOSIS. LONG-TERM SURVIVAL REMAINS UNACCEPTABLE, AND THOSE WHO DO SURVIVE FACE HIGH LATE MORTALITY RISK, NEW CHRONIC TREATMENT-RELATED MEDICAL CONDITIONS, NEUROCOGNITIVE IMPAIRMENTS, AND POOR HEALTH-RELATED QUALITY OF LIFE. UP-FRONT TREATMENT STRATEGIES NOW INTEGRATE MOLECULAR SUBGROUPING WITH STANDARD CLINICO-RADIOLOGICAL FACTORS TO MORE ACTUALLY RISK STRATIFY NEWLY-DIAGNOSED PATIENTS. TO WHAT EXTENT THIS NEW STRATIFICATION WILL LEAD TO IMPROVEMENTS IN TREATMENT OUTCOME WILL BE DETERMINED IN THE COMING YEARS. IN PARALLEL, DISCOVERY AND APPRECIATION FOR MEDULLOBLASTOMA'S INTER- AND INTRA-TUMORAL HETEROGENEITY CONTINUES GROWING. CLINICAL TRIALS TREATING RELAPSED DISEASE NOW ENCOMPASS PRECISION MEDICINE, EPIGENETIC MODIFICATION, AND IMMUNE THERAPY APPROACHES. THE PACIFIC PEDIATRIC NEURO-ONCOLOGY (PNOC) MEDULLOBLASTOMA WORKING GROUP IS COMMITTED TO DEVELOPING CLINICAL TRIALS BASED ON THESE EVOLVING THERAPEUTIC STRATEGIES AND SUPPORTS TRANSLATIONAL EFFORTS BY PNOC RESEARCHERS AND THE MULTI-STAKEHOLDER MEDULLOBLASTOMA COMMUNITY AT LARGE. 2023 8 6838 22 [INTRODUCTION OF TRANSLATIONAL RESEARCH IN OMICS SCIENCE TO CLINICAL ANESTHESIA]. MUCH PROGRESS HAS BEEN MADE IN OMICS RESEARCH FOLLOWING COMPLETION OF THE HUMAN GENOME PROJECT. THIS COMPREHENSIVE ANALYSIS PRODUCED A NEW DISCIPLINE (I.E., BIOINFORMATICS), AND ITS FINDINGS CONTRIBUTED TO THE CLINICAL PRACTICE OF ANESTHESIOLOGY. GENOMES OF PATIENTS SHOW GENETIC VARIATIONS AND MAY PREDICT THE SENSITIVITY TO ANESTHETICS AND ANALGESICS, INCIDENCE OF ADVERSE EFFECTS, AND INTENSITY OF POSTSURGICAL PAIN. CHANGES IN THE TRANSCRIPTOMES OF PATIENTS MAY ALSO REFLECT ANESTHESIA-RELATED EXPRESSION PROFILES OF VARIOUS TYPES OF NEURONS IN THE BRAIN, AND INFORMATION ON SUCH CHANGES MAY CONTRIBUTE TO MOLECULAR TARGETED THERAPY IN ANESTHETIZED PATIENTS. IN ADDITION, NOVEL EPIGENOME RESEARCH MAY EXPLAIN WHY ENVIRONMENTS CHANGE THE PHENOTYPES OF CLINICAL ANESTHESIA. WE CURRENTLY HYPOTHESIZE THAT FEMALE GENDER IS ASSOCIATED WITH DNA METHYLATION IN PAIN-RELATED AND VOMITING-RELATED GENE PROMOTER REGIONS AT THE GENOME-WIDE LEVEL AND THAT EPIGENETIC MECHANISMS ARE INVOLVED IN GENDER DIFFERENCES IN ANESTHESIA PRACTICE. 2013 9 3880 18 KETAMINE: REPURPOSING AND REDEFINING A MULTIFACETED DRUG. THIS SHORT REVIEW WILL HIGHLIGHT RECENT CLINICAL AND BASIC RESEARCH THAT SUPPORTS THE THERAPEUTIC UTILITY OF KETAMINE AS A RAPID-ACTING, LIFE-SAVING ANTIDEPRESSANT AND A VERSATILE ANALGESIC. AFTER 50 YEARS OF USE AS A DISSOCIATIVE ANESTHETIC AND MISUSE AS A STREET DRUG, KETAMINE HAS RE-EMERGED AS A USEFUL OFF-LABEL AGENT FOR AMELIORATING VARIOUS TYPES OF PAIN AND RESISTANT DEPRESSION. IN ADDITION TO ITS ABILITY TO INHIBIT N-METHYL-D-ASPARTATE (NMDA) RECEPTORS, THE DIVERSE ACTIONS OF KETAMINE MIGHT INVOLVE EPIGENETIC MECHANISMS SUCH AS MICRORNA REGULATION. THUS, KETAMINE IS TRANSITIONING FROM BEING THE PHARMACOLOGIST'S NIGHTMARE TO ONE OF THE MOST INTERESTING DEVELOPMENTS IN THE PHARMACOLOGY OF DEPRESSION AND PAIN. 2014 10 6577 17 TREATMENT STRATEGIES FOR COMPLEX BEHAVIORAL INSOMNIA IN CHILDREN WITH NEURODEVELOPMENTAL DISORDERS. PURPOSE OF REVIEW: THIS REVIEW DESCRIBES RECENT RESEARCH IN PEDIATRIC BEHAVIORAL INSOMNIAS IN NEURODEVELOPMENTAL DISORDERS AND THEIR TREATMENT. RECENT FINDINGS: INSOMNIA IN CHILDREN WITH AUTISM SPECTRUM DISORDER (ASD) AND OTHER NEURODEVELOPMENTAL DISORDERS (NDDS) IS TYPICALLY COMPLEX, CHRONIC, AND DIFFICULT TO ADEQUATELY CONTROL. ABNORMALITIES IN GENETIC AND/OR EPIGENETIC REGULATION OF SLEEP/WAKEFULNESS AND ITS TIMING PREDISPOSE PATIENTS WITH NDD TO INSOMNIA, ALTHOUGH POOR SLEEP HYGIENE, MALADAPTIVE ASSOCIATIONS, AND LIMIT-SETTING ARE LIKELY TO CONTRIBUTE. PARENTS ARE AGENTS FOR CHANGE IN PROBLEMATIC SLEEP BEHAVIORS IN PATIENTS WITH NDD. WE REVIEW THE BENEFITS OF BEHAVIORAL THERAPIES AND MELATONIN TO TREAT SLEEP PROBLEMS IN CHILDREN WITH NDD. PROBLEMATIC SLEEP IS SO PREVALENT IN SOME NEURODEVELOPMENTAL SYNDROMES (RETT, ANGELMAN, WILLIAMS, AND SMITH-MAGENIS) THAT IT IS PART OF THEIR DIAGNOSTIC CRITERIA. SUMMARY: CHILDREN AND ADOLESCENTS WITH NEUROLOGICAL DISORDERS FREQUENTLY HAVE COMPLEX SLEEP DISORDERS THAT REQUIRE TREATMENT. UNDERSTANDING THE BASIC PATHOLOGY AND TREATMENT STRATEGIES PROVIDES AN OPPORTUNITY TO IMPROVE WELL BEING AND QUALITY OF LIFE IN THOSE AFFECTED BY NDD AND THEIR FAMILIES. 2013 11 393 21 AN OVERVIEW OF EPIGENETICS IN NURSING. EPIGENETIC CHANGES TO THE GENOME ARE BIOCHEMICAL ALTERATIONS TO THE DNA THAT DO NOT CHANGE AN INDIVIDUAL'S GENOME BUT DO CHANGE AND INFLUENCE GENE EXPRESSION. THE NURSING PROFESSION IS QUALIFIED TO CONDUCT AND INTEGRATE EPIGENETIC-FOCUSED NURSING RESEARCH INTO PRACTICE. THIS ARTICLE DISCUSSES CURRENT EPIGENETIC NURSING RESEARCH, PROVIDES AN OVERVIEW OF HOW EPIGENETIC RESEARCH RELATES TO NURSING PRACTICE, MAKES RECOMMENDATIONS, AND PROVIDES EPIGENETIC ONLINE RESOURCES FOR NURSING RESEARCH. AN OVERVIEW OF MAJOR EPIGENETIC STUDIES IN NURSING (SPECIFIC TO CHILDBIRTH STUDIES, PREECLAMPSIA, METABOLIC SYNDROME, IMMUNOTHERAPY CANCER, AND PAIN) IS PROVIDED, WITH RECOMMENDATIONS ON NEXT STEPS. 2013 12 636 31 BIOLOGICAL SUBSTRATES OF ADDICTION. THIS REVIEW IS AN INTRODUCTION TO ADDICTION, THE REWARD CIRCUITRY, AND LABORATORY ADDICTION MODELS. ADDICTION IS A CHRONIC DISEASE HALLMARKED BY A STATE OF COMPULSIVE DRUG SEEKING THAT PERSISTS DESPITE NEGATIVE CONSEQUENCES. MOST OF THE ADVANCES IN ADDICTION RESEARCH HAVE CENTERED ON THE CANONICAL AND CONTEMPORARY DRUGS OF ABUSE; HOWEVER, ADDICTIONS TO OTHER ACTIVITIES AND STIMULI ALSO EXIST. SUBSTANCES OF ABUSE HAVE THE POTENTIAL TO INDUCE LONG-LASTING CHANGES IN THE BRAIN AT THE BEHAVIORAL, CIRCUIT, AND SYNAPTIC LEVELS. ADDICTION-RELATED BEHAVIORAL CHANGES INVOLVE INITIATION, ESCALATION, AND OBSESSION TO DRUG SEEKING AND MUCH OF THE CURRENT RESEARCH IS FOCUSED ON MAPPING THESE MANIFESTATIONS TO SPECIFIC NEURAL PATHWAYS. DRUG ABUSE IS WELL KNOWN TO RECRUIT COMPONENTS OF THE MESOLIMBIC DOPAMINE SYSTEM, INCLUDING THE NUCLEUS ACCUMBENS AND VENTRAL TEGMENTAL AREA. IN ADDITION, ALTERED FUNCTION OF A WIDE VARIETY OF BRAIN REGIONS IS TIGHTLY ASSOCIATED WITH SPECIFIC MANIFESTATIONS OF DRUG ABUSE. THESE REGIONS PERIPHERAL TO THE MESOLIMBIC PATHWAY LIKELY PLAY A ROLE IN SPECIFIC OBSERVED COMORBIDITIES AND ENDOPHENOTYPES THAT CAN FACILITATE, OR BE CAUSED BY, SUBSTANCE ABUSE. ALTERATIONS IN SYNAPTIC STRUCTURE, FUNCTION, AND CONNECTIVITY, AS WELL AS EPIGENETIC AND GENETIC MECHANISMS ARE THOUGHT TO UNDERLIE THE PATHOLOGIES OF ADDICTION. IN PRECLINICAL MODELS, THESE PERSISTENT CHANGES ARE STUDIED AT THE LEVELS OF MOLECULAR PHARMACOLOGY AND BIOCHEMISTRY, EX VIVO AND IN VIVO ELECTROPHYSIOLOGY, RADIOGRAPHY, AND BEHAVIOR. COORDINATING RESEARCH EFFORTS ACROSS THESE DISCIPLINES AND EXAMINING CELL TYPE- AND CIRCUIT-SPECIFIC PHENOMENA ARE CRUCIAL COMPONENTS FOR TRANSLATING PRECLINICAL FINDINGS TO VIABLE MEDICAL INTERVENTIONS THAT EFFECTIVELY TREAT ADDICTION AND RELATED DISORDERS. WIRES COGN SCI 2014, 5:151-171. DOI: 10.1002/WCS.1273 CONFLICT OF INTEREST: THE AUTHORS HAVE DECLARED NO CONFLICTS OF INTEREST FOR THIS ARTICLE. FOR FURTHER RESOURCES RELATED TO THIS ARTICLE, PLEASE VISIT THE WIRES WEBSITE. 2014 13 5797 22 STEM CELL-BASED THERAPY FOR HIRSCHSPRUNG DISEASE, DO WE HAVE THE GUTS TO TREAT? HIRSCHSPRUNG DISEASE (HSCR) IS A CONGENITAL ANOMALY OF THE COLON THAT RESULTS FROM FAILURE OF ENTERIC NERVOUS SYSTEM FORMATION, LEADING TO A CONSTRICTED DYSFUNCTIONAL SEGMENT OF THE COLON WITH VARIABLE LENGTHS, AND NECESSITATING SURGICAL INTERVENTION. THE UNDERLYING PATHOPHYSIOLOGY INCLUDES A DEFECT IN NEURAL CREST CELLS MIGRATION, PROLIFERATION AND DIFFERENTIATION, WHICH ARE PARTIALLY EXPLAINED BY IDENTIFIED GENETIC AND EPIGENETIC ALTERATIONS. DESPITE THE HIGH SUCCESS RATE OF THE CURATIVE SURGERIES, THEY ARE ASSOCIATED WITH SIGNIFICANT ADVERSE OUTCOMES SUCH AS ENTEROCOLITIS, FECAL SOILING, AND CHRONIC CONSTIPATION. IN ADDITION, SOME PATIENTS SUFFER FROM EXTENSIVE LETHAL VARIANTS OF THE DISEASE, ALL OF WHICH JUSTIFY THE NEED FOR AN ALTERNATIVE CURE. DURING THE LAST 5 YEARS, THERE HAS BEEN CONSIDERABLE PROGRESS IN HSCR STEM CELL-BASED THERAPY RESEARCH. HOWEVER, MANY MAJOR ISSUES REMAIN UNSOLVED. THIS REVIEW WILL PROVIDE CONCISE BACKGROUND INFORMATION ON HSCR, OUTLINE THE FUTURE APPROACHES OF STEM CELL-BASED HSCR THERAPY, REVIEW RECENT KEY PUBLICATIONS, DISCUSS TECHNICAL AND ETHICAL CHALLENGES THE FIELD FACES PRIOR TO CLINICAL TRANSLATION, AND TACKLE SUCH CHALLENGES BY PROPOSING SOLUTIONS AND EVALUATING EXISTING APPROACHES TO PROGRESS FURTHER. 2022 14 2561 29 EPIGENETICS IN THE PERIOPERATIVE PERIOD. THE PERIOPERATIVE PERIOD IS CHARACTERIZED BY PROFOUND CHANGES IN THE BODY'S HOMOEOSTATIC PROCESSES. THIS REVIEW SEEKS TO ADDRESS WHETHER EPIGENETIC MECHANISMS MAY INFLUENCE AN INDIVIDUAL'S REACTION TO SURGERY AND ANAESTHESIA. EVIDENCE FROM ANIMAL AND HUMAN STUDIES SUGGESTS THAT EPIGENETIC MECHANISMS CAN EXPLAIN MANY FACETS OF SUSCEPTIBILITY TO ACUTE AND CHRONIC PAIN, MAKING THEM POTENTIAL THERAPEUTIC TARGETS. MODERN PAIN MANAGEMENT IS STILL BASED UPON OPIATES, AND BOTH THE DEVELOPMENTAL EXPRESSION OF OPIOID RECEPTORS AND OPIOID-INDUCED HYPERALGESIA HAVE BEEN LINKED TO EPIGENETIC MECHANISMS. IN GENERAL, OPIATES SEEM TO INCREASE GLOBAL DNA METHYLATION LEVELS. THIS IS IN CONTRAST TO LOCAL ANAESTHETICS, WHICH HAVE BEEN ASCRIBED A GLOBAL DEMETHYLATING EFFECT. EVEN THOUGH NO DIRECT INVESTIGATIONS HAVE BEEN CARRIED OUT, THE POTENTIAL INFLUENCE OF EPIGENETICS ON THE INFLAMMATORY RESPONSE THAT FOLLOWS SURGERY SEEMS A PROMISING AREA FOR RESEARCH. THERE IS A CONSIDERABLE BODY OF EVIDENCE THAT SUPPORTS THE INVOLVEMENT OF EPIGENETICS IN THE COMPLEX PROCESS OF WOUND HEALING. EPIGENETICS IS AN IMPORTANT EMERGING RESEARCH TOPIC IN PERIOPERATIVE MEDICINE, WITH A HUGE POTENTIAL TO POSITIVELY INFLUENCE PATIENT OUTCOME. 2015 15 2571 28 EPIGENETICS OF CHRONIC PAIN AFTER THORACIC SURGERY. PURPOSE OF REVIEW: CHRONIC PAIN AFTER SURGERY IS A MAJOR PUBLIC HEALTH PROBLEM AND A MAJOR CONCERN FOR PERIOPERATIVE PHYSICIANS. THORACIC SURGERY PRESENTS A UNIQUE CHALLENGE, AS THORACOTOMY IS AMONG THE HIGHEST RISK SURGERIES TO DEVELOP PERSISTENT POSTSURGICAL PAIN. THE PURPOSE OF THIS REVIEW IS TO DISCUSS THE RELEVANCE OF RESEARCH IN PAIN EPIGENETICS TO PATIENTS WITH PERSISTENT PAIN AFTER THORACIC SURGERY. RECENT FINDINGS: RECENT ADVANCES HAVE LINKED CHRONIC PAIN STATES TO GENETIC AND EPIGENETIC CHANGES. PROGRESS IN OUR UNDERSTANDING OF CHRONIC PAIN HAS HIGHLIGHTED THE IMPORTANCE OF IMMUNE MODULATION OF PAIN. IT IS POSSIBLE THAT EPIGENETIC CHANGES DRIVING CHRONIC PAIN OCCUR IN THE PERIOPERATIVE SETTING VIA HISTONE MODIFICATION AND DNA METHYLATION. SUMMARY: THE TRANSITION FROM ACUTE TO CHRONIC PAIN AFTER THORACIC SURGERY MAY BE MEDIATED BY EPIGENETICS. HERE, WE DISCUSS EPIGENETIC MODIFICATIONS THAT HAVE BEEN DISCOVERED IN ANIMAL MODELS OF CHRONIC PAIN THAT MAY PREDISPOSE PATIENTS TO PERSISTENT NEUROPATHIC PAIN AFTER THORACIC SURGERY. 2014 16 6185 28 THE IMPACT OF GENERAL ANESTHESIA ON REDOX STABILITY AND EPIGENETIC INFLAMMATION PATHWAYS: CROSSTALK ON PERIOPERATIVE ANTIOXIDANT THERAPY. WORLDWIDE, THE PREVALENCE OF SURGERY UNDER GENERAL ANESTHESIA HAS SIGNIFICANTLY INCREASED, BOTH BECAUSE OF MODERN ANESTHETIC AND PAIN-CONTROL TECHNIQUES AND BECAUSE OF BETTER DIAGNOSIS AND THE INCREASED COMPLEXITY OF SURGICAL TECHNIQUES. APART FROM DEVELOPING NEW CONCEPTS IN THE SURGICAL FIELD, RESEARCHERS AND CLINICIANS ARE NOW WORKING ON MINIMIZING THE IMPACT OF SURGICAL TRAUMA AND OFFERING MINIMAL INVASIVE PROCEDURES DUE TO THE RECENT DISCOVERIES IN THE FIELD OF CELLULAR AND MOLECULAR MECHANISMS THAT HAVE REVEALED A SYSTEMIC INFLAMMATORY AND PRO-OXIDATIVE IMPACT NOT ONLY IN THE PERIOPERATIVE PERIOD BUT ALSO IN THE LONG TERM, CONTRIBUTING TO MORE DIFFICULT RECOVERY, INCREASED MORBIDITY AND MORTALITY, AND A NEGATIVE FINANCIAL IMPACT. DETAILED MOLECULAR AND CELLULAR ANALYSIS HAS SHOWN AN OVERPRODUCTION OF INFLAMMATORY AND PRO-OXIDATIVE SPECIES, RESPONSIBLE FOR AUGMENTING THE SYSTEMIC INFLAMMATORY STATUS AND MAKING POSTOPERATIVE RECOVERY MORE DIFFICULT. MOREOVER, THERE ARE A SERIES OF CHANGES IN CERTAIN EPIGENETIC STRUCTURES, THE MOST IMPORTANT BEING THE MICRORNAS. THIS REVIEW DESCRIBES THE MOST IMPORTANT MOLECULAR AND CELLULAR MECHANISMS THAT IMPACT THE SURGICAL PATIENT UNDERGOING GENERAL ANESTHESIA, AND IT PRESENTS A SERIES OF ANTIOXIDANT THERAPIES THAT CAN REDUCE SYSTEMIC INFLAMMATION. 2022 17 421 27 ANIMAL MODELS IN EPIGENETIC RESEARCH: INSTITUTIONAL ANIMAL CARE AND USE COMMITTEE CONSIDERATIONS ACROSS THE LIFESPAN. THE RAPID EXPANSION AND EVOLUTION OF EPIGENETICS AS A CORE SCIENTIFIC DISCIPLINE HAVE RAISED NEW QUESTIONS ABOUT HOW ENDOGENOUS AND ENVIRONMENTAL FACTORS CAN INFORM THE MECHANISMS THROUGH WHICH BIOLOGICAL FORM AND FUNCTION ARE REGULATED. EXISTING AND PROPOSED ANIMAL MODELS USED FOR EPIGENETIC RESEARCH HAVE TARGETED A MYRIAD OF HEALTH AND DISEASE ENDPOINTS THAT MAY BE ACUTE, CHRONIC, AND TRANSGENERATIONAL IN NATURE. INITIATING EVENTS AND OUTCOMES MAY EXTEND ACROSS THE ENTIRE LIFESPAN TO ELICIT UNANTICIPATED PHENOTYPES THAT ARE OF PARTICULAR CONCERN TO INSTITUTIONAL ANIMAL CARE AND USE COMMITTEES (IACUCS). THE DYNAMICS AND PLASTICITY OF EPIGENETIC MECHANISMS PRODUCE EFFECTS AND CONSEQUENCES THAT ARE MANIFEST DIFFERENTIALLY WITHIN DISCREET SPATIAL AND TEMPORAL CONTEXTS, INCLUDING PRENATAL DEVELOPMENT, STEM CELLS, ASSISTED REPRODUCTIVE TECHNOLOGIES, PRODUCTION OF SEXUAL DIMORPHISMS, SENESCENCE, AND OTHERS. MANY DIETARY AND NUTRITIONAL INTERVENTIONS HAVE ALSO BEEN SHOWN TO HAVE A SIGNIFICANT IMPACT ON BIOLOGICAL FUNCTIONS AND DISEASE SUSCEPTIBILITIES THROUGH ALTERED EPIGENETIC PROGRAMMING. THE ENVIRONMENTAL, CHEMICAL, TOXIC, THERAPEUTIC, AND PSYCHOSOCIAL STRESSORS USED IN ANIMAL STUDIES TO ELICIT EPIGENETIC CHANGES CAN BECOME EXTREME AND SHOULD RAISE IACUC CONCERNS FOR THE WELL-BEING AND PROPER CARE OF ALL RESEARCH ANIMALS INVOLVED. EPIGENETICS RESEARCH IS RAPIDLY BECOMING AN INTEGRAL PART OF THE SEARCH FOR MECHANISMS IN EVERY MAJOR AREA OF BIOMEDICAL AND BEHAVIORAL RESEARCH AND WILL FOSTER THE CONTINUED DEVELOPMENT OF NEW ANIMAL MODELS. FROM THE IACUC PERSPECTIVE, CARE MUST BE TAKEN TO ACKNOWLEDGE THE PARTICULAR NEEDS AND CONCERNS CREATED BY SUPERIMPOSITION OF EPIGENETIC MECHANISMS OVER DIVERSE FIELDS OF INVESTIGATION TO ENSURE THE PROPER CARE AND USE OF ANIMALS WITHOUT IMPEDING SCIENTIFIC PROGRESS. 2012 18 4846 23 OPIATE ADDICTION AND COCAINE ADDICTION: UNDERLYING MOLECULAR NEUROBIOLOGY AND GENETICS. ADDICTIVE DISEASES, INCLUDING ADDICTION TO HEROIN, PRESCRIPTION OPIOIDS, OR COCAINE, POSE MASSIVE PERSONAL AND PUBLIC HEALTH COSTS. ADDICTIONS ARE CHRONIC RELAPSING DISEASES OF THE BRAIN CAUSED BY DRUG-INDUCED DIRECT EFFECTS AND PERSISTING NEUROADAPTATIONS AT THE EPIGENETIC, MRNA, NEUROPEPTIDE, NEUROTRANSMITTER, OR PROTEIN LEVELS. THESE NEUROADAPTATIONS, WHICH CAN BE SPECIFIC TO DRUG TYPE, AND THEIR RESULTANT BEHAVIORS ARE MODIFIED BY VARIOUS INTERNAL AND EXTERNAL ENVIRONMENTAL FACTORS, INCLUDING STRESS RESPONSIVITY, ADDICT MINDSET, AND SOCIAL SETTING. SPECIFIC GENE VARIANTS, INCLUDING VARIANTS ENCODING PHARMACOLOGICAL TARGET PROTEINS OR GENES MEDIATING NEUROADAPTATIONS, ALSO MODIFY VULNERABILITY AT PARTICULAR STAGES OF ADDICTION. GREATER UNDERSTANDING OF THESE INTERACTING FACTORS THROUGH LABORATORY-BASED AND TRANSLATIONAL STUDIES HAVE THE POTENTIAL TO OPTIMIZE EARLY INTERVENTIONS FOR THE THERAPY OF CHRONIC ADDICTIVE DISEASES AND TO REDUCE THE BURDEN OF RELAPSE. HERE, WE REVIEW THE MOLECULAR NEUROBIOLOGY AND GENETICS OF OPIATE ADDICTION, INCLUDING HEROIN AND PRESCRIPTION OPIOIDS, AND COCAINE ADDICTION. 2012 19 4645 24 NEUROPATHIC PAIN: FROM MECHANISMS TO TREATMENT. NEUROPATHIC PAIN CAUSED BY A LESION OR DISEASE OF THE SOMATOSENSORY NERVOUS SYSTEM IS A COMMON CHRONIC PAIN CONDITION WITH MAJOR IMPACT ON QUALITY OF LIFE. EXAMPLES INCLUDE TRIGEMINAL NEURALGIA, PAINFUL POLYNEUROPATHY, POSTHERPETIC NEURALGIA, AND CENTRAL POSTSTROKE PAIN. MOST PATIENTS COMPLAIN OF AN ONGOING OR INTERMITTENT SPONTANEOUS PAIN OF, FOR EXAMPLE, BURNING, PRICKING, SQUEEZING QUALITY, WHICH MAY BE ACCOMPANIED BY EVOKED PAIN, PARTICULAR TO LIGHT TOUCH AND COLD. ECTOPIC ACTIVITY IN, FOR EXAMPLE, NERVE-END NEUROMA, COMPRESSED NERVES OR NERVE ROOTS, DORSAL ROOT GANGLIA, AND THE THALAMUS MAY IN DIFFERENT CONDITIONS UNDERLIE THE SPONTANEOUS PAIN. EVOKED PAIN MAY SPREAD TO NEIGHBORING AREAS, AND THE UNDERLYING PATHOPHYSIOLOGY INVOLVES PERIPHERAL AND CENTRAL SENSITIZATION. MALADAPTIVE STRUCTURAL CHANGES AND A NUMBER OF CELL-CELL INTERACTIONS AND MOLECULAR SIGNALING UNDERLIE THE SENSITIZATION OF NOCICEPTIVE PATHWAYS. THESE INCLUDE ALTERATION IN ION CHANNELS, ACTIVATION OF IMMUNE CELLS, GLIAL-DERIVED MEDIATORS, AND EPIGENETIC REGULATION. THE MAJOR CLASSES OF THERAPEUTICS INCLUDE DRUGS ACTING ON ALPHA(2)DELTA SUBUNITS OF CALCIUM CHANNELS, SODIUM CHANNELS, AND DESCENDING MODULATORY INHIBITORY PATHWAYS. 2021 20 609 23 BEYOND MOR: CAN INDUCTION OF DOPAMINE HOMEOSTASIS ALONG WITH ELECTROTHERAPY ATTENUATE THE OPIOID CRISIS? ONE IMPORTANT AREA FOR CONSIDERATION ESPECIALLY IN TERMS OF COMBATING THE ONGOING NEVER ENDING OPIOID CRISIS, RELATES TO NOVEL NEWER ASSESSMENTS FOR ALL ADDICTIVE BEHAVIORS BOTH SUBSTANCE AND NON-SUBSTANCE BEHAVIORS (RDS). IT IS VERY IMPORTANT TO IDENTIFY EARLY IN ONE'S LIFE THE POSSIBILITY OF, BECAUSE OF KNOWN DNA ANTECEDENTS, THE PRESENCE OF PRE-ADDICTION. THE DEVELOPMENT OF THE GENETIC ADDICTION RISK SEVERITY (GARS) TEST, BLUM'S GROUP BELIEVES THAT THIS TYPE OF TESTING SHOULD BE THE "STANDARD OF CARE" FOLLOWING ADDITIONAL STUDIES. UNDERSTANDABLY THAT WHILE POLYMORPHISMS IN THE MU-OPIOID RECEPTOR (MOR) IS OF REAL CONCERN IN TERMS OF SETTING PEOPLE UP FOR PREDISPOSITION TO OPIOID DEPENDENCE, THE GENETIC AND EPIGENETIC STATUS OF DOPAMINERGIC FUNCTION MUST BE CONSIDERED AS WELL. WHILE THIS SOUNDS BOLD (WHICH IT IS) THE RESULTS SHOULD BE PROTECTED BY THE G.I. N. A. LAW ENACTED IN THE USA IN 2011. ONE AVENUE OF FURTHER INVESTIGATION, INSTEAD OF PROVIDING POWERFUL OPIOIDS FOR OPIOID DEPENDENCE, IS TO SEEK OUT NON-ADDICTIVE ALTERNATIVES. ACCORDINGLY, OTHER NON-ADDICTIVE MODALITIES INCLUDING GENETIC GUIDED KB220 (AMINO-ACID-ENKEPHALINASE-N-ACETYLCYSTEINE-NAD), NON-INVASIVE RTMS FOR PSYCHIATRY AND PAIN, EPIGENETIC REMODELING, GENE EDITS, NON-INVASIVE H-WAVE FOR PAIN MANAGEMENT AND ENHANCED FUNCTIONALITY, BRAIN SPOTTING, COGNITIVE BEHAVIORAL THERAPY AWARENESSS INTEGRATION THERAPY, NUCALM, TRAUMA THERAPY, AWARENESS TOOLS, GENOGRAMS, EXERCISE, SPORTS, FITNESS PROGRAMS (ONE HOUR PER DAY), LIGHT THERAPY AND EVEN LAUGHING THERAPY AS WELL AS ANY OTHER KNOWN MODALITIES THAT CAN INDUCE REWARD SYMMETRY. WHILE THE SHORT TERM USE OF OPIOIDS FOR OPIOID DEPENDENCE TO REDUCE HARM IS CERTAINLY ACCEPTABLE, CLINICIANS SHOULD CONSIDER A BETTER LONG-TERM PLAN. 2023