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  1. Article ; Online: Gadgeteering for Pain Relief: The 2021 John W. Severinghaus Lecture on Translational Science.

    Eisenach, James C

    Anesthesiology

    2022  Volume 136, Issue 6, Page(s) 888–900

    Abstract: In this first memorial lecture after John Severinghaus's death in 2021, the author traces his journey as a physician-scientist, using the framework of the hero's journey as described by the author Joseph Campbell 40 to 50 yr ago, and parallels that ... ...

    Abstract In this first memorial lecture after John Severinghaus's death in 2021, the author traces his journey as a physician-scientist, using the framework of the hero's journey as described by the author Joseph Campbell 40 to 50 yr ago, and parallels that journey to his own. The author discusses how each were gadgeteers: Severinghaus in a creative engineering way, while the author's approach was asking simple questions translating basic research in pain from animals to humans. The classic hero's journey of departure to achieve a goal, then trials, transformation, and finally, returning with benefits to the individual and others is translated to the common physician-scientist career with motivations progressing from "I will show" to "I wonder if" to "I wonder why." Critical to this journey is self-questioning, openness to new ideas, and realizing that progress occurs through failure as much as success.
    MeSH term(s) Animals ; Motivation ; Pain ; Translational Science, Biomedical
    Language English
    Publishing date 2022-04-28
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 269-0
    ISSN 1528-1175 ; 0003-3022
    ISSN (online) 1528-1175
    ISSN 0003-3022
    DOI 10.1097/ALN.0000000000004207
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  2. Article ; Online: Effects of systemic oxytocin administration on ultraviolet B-induced nociceptive hypersensitivity and tactile hyposensitivity in mice.

    Boada, M Danilo / Gutierrez, Silvia / Eisenach, James C

    Molecular pain

    2024  Volume 20, Page(s) 17448069241226553

    Abstract: Ultraviolet B (UVB) radiation induces cutaneous inflammation, leading to thermal and mechanical hypersensitivity. Here, we examine the mechanical properties and profile of tactile and nociceptive peripheral afferents functionally disrupted by this injury ...

    Abstract Ultraviolet B (UVB) radiation induces cutaneous inflammation, leading to thermal and mechanical hypersensitivity. Here, we examine the mechanical properties and profile of tactile and nociceptive peripheral afferents functionally disrupted by this injury and the role of oxytocin (OXT) as a modulator of this disruption. We recorded intracellularly from L4 afferents innervating the irradiated area (5.1 J/cm
    MeSH term(s) Mice ; Male ; Animals ; Oxytocin/pharmacology ; Oxytocin/therapeutic use ; Nociception ; Mice, Inbred C57BL ; Touch/physiology ; Skin/innervation ; Mechanoreceptors ; Nociceptors/physiology
    Chemical Substances Oxytocin (50-56-6)
    Language English
    Publishing date 2024-01-03
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2174252-2
    ISSN 1744-8069 ; 1744-8069
    ISSN (online) 1744-8069
    ISSN 1744-8069
    DOI 10.1177/17448069241226553
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  3. Article ; Online: Preliminary results from a randomized, controlled, cross-over trial of intrathecal oxytocin for neuropathic pain.

    Eisenach, James C / Curry, Regina S / Houle, Timothy T

    Pain medicine (Malden, Mass.)

    2023  Volume 24, Issue 9, Page(s) 1058–1065

    Abstract: Objective: Compare intrathecal oxytocin, 100 µg to placebo on ongoing neuropathic pain and mechanical hyperalgesia and allodynia.: Study design: Randomized, controlled, double-blind cross-over.: Setting: Clinical research unit.: Subjects: ... ...

    Abstract Objective: Compare intrathecal oxytocin, 100 µg to placebo on ongoing neuropathic pain and mechanical hyperalgesia and allodynia.
    Study design: Randomized, controlled, double-blind cross-over.
    Setting: Clinical research unit.
    Subjects: Individuals aged 18 to 70 years with neuropathic pain for at least 6 months.
    Methods: Individuals received intrathecal injections of oxytocin and saline, separated by at least 7 days, and ongoing pain in neuropathic area (VAS [visual analog scale]) and areas of hypersensitivity to von Frey filament and cotton wisp brushing were measured for 4 hours. Primary outcome was VAS pain in the first 4 hours after injection, analyzed by linear mixed effects model. Secondary outcomes were verbal pain intensity scores at daily intervals for 7 days and areas of hypersensitivity and elicited pain for 4 hours after injections.
    Results: The study was stopped early after completion of 5 of 40 subjects planned due to slow recruitment and funding limitations. Pain intensity prior to injection was 4.75 ± 0.99 and modeled pain intensity decreased more after oxytocin than placebo to 1.61 ± 0.87 and 2.49 ± 0.87, respectively (P = .003). Daily pain scores were lower in the week following injection of oxytocin than saline (2.53 ± 0.89 vs 3.66 ± 0.89; P = .001). Allodynic area decreased by 11%, but hyperalgesic area increased by 18% after oxytocin compared to placebo. There were no study drug related adverse effects.
    Conclusion: Although limited by the small number of subjects studied, oxytocin reduced pain more than placebo in all subjects. Further study of spinal oxytocin in this population is warranted.
    Trial registration: This study was registered at ClinicalTrials.gov on 03/27/2014 (NCT02100956). The first subject was studied on 06/25/2014.
    MeSH term(s) Humans ; Oxytocin/therapeutic use ; Cross-Over Studies ; Neuralgia/drug therapy ; Hyperalgesia/drug therapy ; Pain Measurement ; Double-Blind Method
    Chemical Substances Oxytocin (50-56-6)
    Language English
    Publishing date 2023-04-21
    Publishing country England
    Document type Randomized Controlled Trial ; Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2015903-1
    ISSN 1526-4637 ; 1526-2375
    ISSN (online) 1526-4637
    ISSN 1526-2375
    DOI 10.1093/pm/pnad051
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  4. Article ; Online: Ketamine fails to prevent postoperative delirium.

    Eisenach, James C

    Lancet (London, England)

    2017  Volume 390, Issue 10091, Page(s) 206–208

    Language English
    Publishing date 2017-07-15
    Publishing country England
    Document type Journal Article
    ZDB-ID 3306-6
    ISSN 1474-547X ; 0023-7507 ; 0140-6736
    ISSN (online) 1474-547X
    ISSN 0023-7507 ; 0140-6736
    DOI 10.1016/S0140-6736(17)31504-0
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  5. Article ; Online: In Reply.

    Eisenach, James C

    Anesthesiology

    2016  Volume 125, Issue 5, Page(s) 1074–1075

    Language English
    Publishing date 2016-11
    Publishing country United States
    Document type Journal Article
    ZDB-ID 269-0
    ISSN 1528-1175 ; 0003-3022
    ISSN (online) 1528-1175
    ISSN 0003-3022
    DOI 10.1097/ALN.0000000000001300
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  6. Article ; Online: Improving Preclinical Development of Novel Interventions to Treat Pain: Insanity Is Doing the Same Thing Over and Over and Expecting Different Results.

    Eisenach, James C / Rice, Andrew S C

    Anesthesia and analgesia

    2022  Volume 135, Issue 6, Page(s) 1128–1136

    Abstract: Preclinical pain research has applied state-of-the-art methods over the past 40 years to describe, characterize, and image molecules, cells, and circuits in rodents to understand the pathophysiology of chronic pain. Despite generating a plethora of novel ...

    Abstract Preclinical pain research has applied state-of-the-art methods over the past 40 years to describe, characterize, and image molecules, cells, and circuits in rodents to understand the pathophysiology of chronic pain. Despite generating a plethora of novel analgesic targets, pharmaceuticals for chronic pain treatment remain largely limited to the same 6 drug classes as present 40 years ago. It is possible that 40 years of effort has brought us to the verge of a paradigm shift and an explosion of novel analgesic drug classes with remarkable safety, efficacy, and tolerability. We think it more likely that advances will not occur until we follow the description of exciting discoveries with hypothesis testing using clinically relevant preclinical animal models and ethologically relevant outcome measures, which better reflect the clinical characteristics of chronic pain syndromes. Furthermore, to be valuable, experiments using such models must be conducted to the highest levels of internal validity, rigor, and reproducibility. Efforts by funders, most recently the Helping End Addiction Long-Term by the National Institutes of Health, aim to address some of these challenges and enhance communication and collaboration between preclinical and clinical investigators. However, the greater problem is a culture that emphasizes novelty and number of publications over scientific rigor and robust replication leading to a high likelihood of false-positive results. A path forward is provided by the evolution of clinical research beginning 50 years ago that resulted in methods to reduce bias and enhance transparency and ethics of reporting, moving from case reports to randomized controlled trials to innovative study designs with a focus on rigor, generalizability, and reproducibility. We argue that culture changed in clinical science in part because powerful forces outside the peer review system, especially from federal regulators that approve new drugs and human studies committees that addressed ethical failures of earlier research, mandated change in studies within their purview. Whether an external force will affect change in peclinical pain research is unclear.
    MeSH term(s) Animals ; Humans ; Chronic Pain/diagnosis ; Chronic Pain/drug therapy ; Reproducibility of Results ; Pain Management ; Analgesics ; Bias ; Randomized Controlled Trials as Topic
    Chemical Substances Analgesics
    Language English
    Publishing date 2022-11-16
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 80032-6
    ISSN 1526-7598 ; 0003-2999
    ISSN (online) 1526-7598
    ISSN 0003-2999
    DOI 10.1213/ANE.0000000000006249
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  7. Article ; Online: Hypotension duration and vasopressor requirements following intrathecal oxytocin for Total hip arthroplasty: Secondary analysis of a randomized controlled trial.

    Henshaw, Daryl S / Khanna, Ashish K / Edwards, Christopher J / Eisenach, James C

    Journal of clinical anesthesia

    2023  Volume 89, Page(s) 111189

    Abstract: Introduction: A recent publication investigating intrathecal oxytocin, 100 μg, administered immediately prior to a spinal anesthetic in patients undergoing primary total hip arthroplasty surgery demonstrated a reduction in disability for 3-weeks, ... ...

    Abstract Introduction: A recent publication investigating intrathecal oxytocin, 100 μg, administered immediately prior to a spinal anesthetic in patients undergoing primary total hip arthroplasty surgery demonstrated a reduction in disability for 3-weeks, increased walking distance at 8-weeks, and earlier opioid cessation. This secondary analysis study was undertaken to assess the acute cardiovascular safety and analgesic efficacy of intrathecal oxytocin in this study population.
    Methods: 90 patients were included in the analysis (44 randomized to spinal oxytocin and 46 to placebo [saline]). Data collected prospectively during the previously published study were supplemented with additional retrospectively collected data. The primary outcomes were comparisons of the duration of hypotension (minutes with mean arterial pressure < 65 mmHg) and cumulative vasopressor requirements during the initial 60 min following spinal placement. Secondary outcomes included hypotension durations and vasopressor requirements at later time points, perioperative fluid administration, physical therapy metrics, time to first opioid administration, cumulative opioid consumption through 24 h, and verbal pain scores through 24 h.
    Results: The duration of hypotension during the first 60 min following spinal placement did not differ between intrathecal oxytocin and placebo groups (12.2 ± 10.7 vs 14.0 ± 13.0 min, respectively; p = 0.476). There was also no difference in cumulative vasopressor requirements (1303 ± 883 vs 1156 ± 818 μg [phenylephrine equivalents]; p = 0.413) during that time period. No group differences were found for any of the investigated secondary outcomes.
    Conclusion: The administration of 100 μg of intrathecal oxytocin does not significantly impact the duration of hypotension or the need for vasopressor agents when given as a component of a spinal anesthetic. The oxytocin and placebo groups also did not differ in regards to physical therapy related metrics, time to first opioid administration, cumulative opioids at 24-h, or pain scores through 24-h. What is already known on this topic: Rapid intravenous oxytocin causes hypotension after cesarean delivery, but intrathecal oxytocin does not cause hypotension in healthy volunteers.
    What this study adds: Compared to saline control, intrathecal oxytocin, 100 μg did not increase the duration of hypotension or vasopressor requirements in patients during total hip arthroplasty. How this study might affect research, practice, or policy: Lack of hypotension from intrathecal oxytocin in this study supports future investigations to further explore its potential benefits, in terms of both analgesia and functional recovery following surgery.
    MeSH term(s) Pregnancy ; Female ; Humans ; Analgesics, Opioid ; Oxytocin/adverse effects ; Retrospective Studies ; Arthroplasty, Replacement, Hip/adverse effects ; Injections, Spinal ; Hypotension/chemically induced ; Hypotension/drug therapy ; Anesthesia, Spinal/adverse effects ; Vasoconstrictor Agents/adverse effects ; Pain/drug therapy ; Anesthetics ; Double-Blind Method
    Chemical Substances Analgesics, Opioid ; Oxytocin (50-56-6) ; Vasoconstrictor Agents ; Anesthetics
    Language English
    Publishing date 2023-06-23
    Publishing country United States
    Document type Randomized Controlled Trial ; Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 1011618-7
    ISSN 1873-4529 ; 0952-8180
    ISSN (online) 1873-4529
    ISSN 0952-8180
    DOI 10.1016/j.jclinane.2023.111189
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  8. Article ; Online: Without Science There Is Little Art in Anesthesiology: 2015 Rovenstine Lecture.

    Eisenach, James C

    Anesthesiology

    2016  Volume 124, Issue 6, Page(s) 1205–1207

    Language English
    Publishing date 2016-06
    Publishing country United States
    Document type Journal Article
    ZDB-ID 269-0
    ISSN 1528-1175 ; 0003-3022
    ISSN (online) 1528-1175
    ISSN 0003-3022
    DOI 10.1097/ALN.0000000000001116
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  9. Article ; Online: Seeding of breast cancer cell line (MDA-MB-231

    Gutierrez, Silvia / Eisenach, James C / Boada, M Danilo

    Molecular pain

    2021  Volume 17, Page(s) 17448069211024082

    Abstract: Some types of cancer are commonly associated with intense pain even at the early stages of the disease. The mandible is particularly vulnerable to metastasis from breast cancer, and this process has been studied using a bioluminescent human breast cancer ...

    Abstract Some types of cancer are commonly associated with intense pain even at the early stages of the disease. The mandible is particularly vulnerable to metastasis from breast cancer, and this process has been studied using a bioluminescent human breast cancer cell line (MDA-MB-231
    MeSH term(s) Animals ; Breast Neoplasms ; Calcitonin Gene-Related Peptide ; Cell Line ; Female ; Humans ; Mandible ; Substance P ; Trigeminal Ganglion ; Tumor Microenvironment
    Chemical Substances Substance P (33507-63-0) ; Calcitonin Gene-Related Peptide (JHB2QIZ69Z)
    Language English
    Publishing date 2021-05-27
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2174252-2
    ISSN 1744-8069 ; 1744-8069
    ISSN (online) 1744-8069
    ISSN 1744-8069
    DOI 10.1177/17448069211024082
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  10. Article ; Online: Anesthesiology: Attracting the Best New Science in the Specialty.

    Eisenach, James C

    Anesthesiology

    2015  Volume 122, Issue 6, Page(s) 1198–1200

    MeSH term(s) Anesthesiology/trends ; Internship and Residency ; Periodicals as Topic ; Publishing/standards
    Language English
    Publishing date 2015-06
    Publishing country United States
    Document type Editorial
    ZDB-ID 269-0
    ISSN 1528-1175 ; 0003-3022
    ISSN (online) 1528-1175
    ISSN 0003-3022
    DOI 10.1097/ALN.0000000000000668
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