Browsing by Author "Buchheit, Thomas"

Now showing 1 - 7 of 7
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    Differential expression of systemic inflammatory mediators in amputees with chronic residual limb pain.
    (Pain, 2017-01) Chamessian, Alexander; Van de Ven, Thomas; Buchheit, Thomas; Hsia, Hung-Lun; McDuffie, Mary; Gamazon, Eric R; Walsh, Colin; Bruehl, Stephen; Buckenmaier, Chester 'Trip'; Shaw, Andrew
    Chronic postsurgical pain impacts most amputees, with more than half experiencing neuralgic residual limb pain. The transition from normal acute postamputation pain to chronic residual limb pain likely involves both peripheral and central inflammatory mechanisms. As part of the Veterans Integrated Pain Evaluation Research study, we investigated links between systemic inflammatory mediator levels and chronic residual limb pain. Subjects included 36 recent active duty military traumatic amputees with chronic residual limb pain and 40 without clinically significant pain. Blood samples were obtained and plasma concentrations of an array of inflammatory mediators were analyzed. Residual limb pain intensity and pain catastrophizing were assessed to examine associations with inflammatory mediators. Pro-inflammatory mediators including tumor necrosis factor (TNF)-α, TNF-β, interleukin (IL)-8, ICAM-1, Tie2, CRP, and SAA were elevated in patients with chronic residual limb pain. Across all patients, residual limb pain intensity was associated positively with levels of several proinflammatory mediators (IL-8, TNF-α, IL-12, TNF-β, PIGF, Tie2, SAA, and ICAM-1), and inversely with concentrations of the anti-inflammatory mediator IL-13, as well as IL-2 and Eotaxin-3. Pain catastrophizing correlated positively with IL-8, IL-12, TNF-β, PIGF, and ICAM-1, and inversely with IL-13. Significant associations between catastrophizing and residual limb pain intensity were partially mediated by TNF-α, TNF- β, SAA, and ICAM-1 levels. Results suggest that chronic postamputation residual limb pain is associated with excessive inflammatory response to injury or to inadequate resolution of the postinjury inflammatory state. Impact of pain catastrophizing on residual limb pain may be because of part to common underlying inflammatory mechanisms.
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    DNA methylation profiles are associated with complex regional pain syndrome after traumatic injury.
    (Pain, 2019-10) Bruehl, Stephen; Gamazon, Eric R; Van de Ven, Thomas; Buchheit, Thomas; Walsh, Colin G; Mishra, Puneet; Ramanujan, Krishnan; Shaw, Andrew
    Factors contributing to development of complex regional pain syndrome (CRPS) are not fully understood. This study examined possible epigenetic mechanisms that may contribute to CRPS after traumatic injury. DNA methylation profiles were compared between individuals developing CRPS (n = 9) and those developing non-CRPS neuropathic pain (n = 38) after undergoing amputation following military trauma. Linear Models for Microarray (LIMMA) analyses revealed 48 differentially methylated cytosine-phosphate-guanine dinucleotide (CpG) sites between groups (unadjusted P's < 0.005), with the top gene COL11A1 meeting Bonferroni-adjusted P < 0.05. The second largest differential methylation was observed for the HLA-DRB6 gene, an immune-related gene linked previously to CRPS in a small gene expression study. For all but 7 of the significant CpG sites, the CRPS group was hypomethylated. Numerous functional Gene Ontology-Biological Process categories were significantly enriched (false discovery rate-adjusted q value <0.15), including multiple immune-related categories (eg, activation of immune response, immune system development, regulation of immune system processes, and antigen processing and presentation). Differentially methylated genes were more highly connected in human protein-protein networks than expected by chance (P < 0.05), supporting the biological relevance of the findings. Results were validated in an independent sample linking a DNA biobank with electronic health records (n = 126 CRPS phenotype, n = 19,768 non-CRPS chronic pain phenotype). Analyses using PrediXcan methodology indicated differences in the genetically determined component of gene expression in 7 of 48 genes identified in methylation analyses (P's < 0.02). Results suggest that immune- and inflammatory-related factors might confer risk of developing CRPS after traumatic injury. Validation findings demonstrate the potential of using electronic health records linked to DNA for genomic studies of CRPS.
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    Epigenetics and the transition from acute to chronic pain.
    (Pain medicine (Malden, Mass.), 2012-11) Buchheit, Thomas; Van de Ven, Thomas; Shaw, Andrew
    The objective of this study was to review the epigenetic modifications involved in the transition from acute to chronic pain and to identify potential targets for the development of novel, individualized pain therapeutics.Epigenetics is the study of heritable modifications in gene expression and phenotype that do not require a change in genetic sequence to manifest their effects. Environmental toxins, medications, diet, and psychological stresses can alter epigenetic processes such as DNA methylation, histone acetylation, and RNA interference. As epigenetic modifications potentially play an important role in inflammatory cytokine metabolism, steroid responsiveness, and opioid sensitivity, they are likely key factors in the development of chronic pain. Although our knowledge of the human genetic code and disease-associated polymorphisms has grown significantly in the past decade, we have not yet been able to elucidate the mechanisms that lead to the development of persistent pain after nerve injury or surgery.This is a focused literature review of epigenetic science and its relationship to chronic pain.Significant laboratory and clinical data support the notion that epigenetic modifications are affected by the environment and lead to differential gene expression. Similar to mechanisms involved in the development of cancer, neurodegenerative disease, and inflammatory disorders, the literature endorses an important potential role for epigenetics in chronic pain.Epigenetic analysis may identify mechanisms critical to the development of chronic pain after injury, and may provide new pathways and target mechanisms for future drug development and individualized medicine.
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    Future therapies and the expanding role for diagnostic ultrasound
    (Current Opinion in Anaesthesiology, 2016-01-01) Buchheit, Thomas
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    Pain Phenotypes and Associated Clinical Risk Factors Following Traumatic Amputation: Results from Veterans Integrated Pain Evaluation Research (VIPER).
    (Pain medicine (Malden, Mass.), 2016-01) Buchheit, Thomas; Van de Ven, Thomas; Hsia, Hung-Lun John; McDuffie, Mary; MacLeod, David B; White, William; Chamessian, Alexander; Keefe, Francis J; Buckenmaier, Chester Trip; Shaw, Andrew D
    OBJECTIVE:To define clinical phenotypes of postamputation pain and identify markers of risk for the development of chronic pain. DESIGN:Cross-sectional study of military service members enrolled 3-18 months after traumatic amputation injury. SETTING:Military Medical Center. SUBJECTS:124 recent active duty military service members. METHODS:Study subjects completed multiple pain and psychometric questionnaires to assess the qualities of phantom and residual limb pain. Medical records were reviewed to determine the presence/absence of a regional catheter near the time of injury. Subtypes of residual limb pain (somatic, neuroma, and complex regional pain syndrome) were additionally analyzed and associated with clinical risk factors. RESULTS:A majority of enrolled patients (64.5%) reported clinically significant pain (pain score ≥ 3 averaged over previous week). 61% experienced residual limb pain and 58% experienced phantom pain. When analysis of pain subtypes was performed in those with residual limb pain, we found evidence of a sensitized neuroma in 48.7%, somatic pain in 40.8%, and complex regional pain syndrome in 19.7% of individuals. The presence of clinically significant neuropathic residual limb pain was associated with symptoms of PTSD and depression. Neuropathic pain of any severity was associated with symptoms of all four assessed clinical risk factors: depression, PTSD, catastrophizing, and the absence of regional analgesia catheter. CONCLUSIONS:Most military service members in this cohort suffered both phantom and residual limb pain following amputation. Neuroma was a common cause of neuropathic pain in this group. Associated risk factors for significant neuropathic pain included PTSD and depression. PTSD, depression, catastrophizing, and the absence of a regional analgesia catheter were associated with neuropathic pain of any severity.
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    Residual limb pain is not a diagnosis: a proposed algorithm to classify postamputation pain.
    (The Clinical journal of pain, 2013-06) Clarke, Collin; Lindsay, David R; Pyati, Srinivas; Buchheit, Thomas
    BACKGROUND: Although postamputation pain (PAP) syndromes have been described since the 16th century, taxonomy of these conditions remains ill-defined. The term "Residual Limb Pain" fails to distinguish between distinct diagnostic entities such as neuroma, complex regional pain syndrome, and somatic pathology. Even phantom limb pain (PLP), although easily distinguished from residual limb pain (RLP), has not been consistently delineated from other PAP syndromes. METHODS: A systematic review of the literature was conducted to identify the degree of delineation of various post amputation pain states and what diagnostic criteria were utilized if any. Furthermore, papers that involved treatment modalities were reviewed to determine efficacy of treatment. RESULTS: Of the 151 papers reviewed, none further categorized RLP into more specific diagnostic criteria. Furthermore, the literature contains numerous case reports, case series, letters to the editors, and grossly underpowered studies demonstrating significant positive results, yet few high-quality randomized controlled trials. CONCLUSIONS: Describing and defining the distinct clinical entities, intuitively, is a prerequisite to developing optimal treatments. The reported variation in the incidence of PAP phenomena may well represent inconsistency in assessment tools and diagnostic categories rather than variation in prevalence of these conditions. In this paper, we review the historical evolution of the current understanding of these syndromes and propose an algorithm for uniform classification.
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    The Impact of Surgical Amputation and Valproic Acid on Pain and Functional Trajectory: Results from the Veterans Integrated Pain Evaluation Research (VIPER) Randomized, Double-Blinded Placebo-Controlled Trial.
    (Pain medicine (Malden, Mass.), 2019-05-02) Buchheit, Thomas; Hsia, Hung-Lun John; Cooter, Mary; Shortell, Cynthia; Kent, Michael; McDuffie, Mary; Shaw, Andrew; Buckenmaier, Chester Trip; Van de Ven, Thomas
    OBJECTIVE:To determine if the perioperative administration of valproic acid reduces the incidence of chronic pain three months after amputation or revision surgery. DESIGN:Multicenter, randomized, double-blind, placebo-controlled trial. SETTING:Academic, military, and veteran medical centers. SUBJECTS:One hundred twenty-eight patients undergoing amputation or amputation revision surgery at Duke University Hospital, Walter Reed National Military Medical Center, or the Durham Veterans Affairs Medical Center for either medical disease or trauma. METHODS:Patients were randomized to placebo or valproic acid for the duration of hospitalization and treated with multimodal analgesic care, including regional anesthetic blockade. Primary outcome was the proportion of patients with chronic pain at three months (average numeric pain score intensity of 3/10 or greater). Secondary outcomes included functional trajectories (assessed with the Brief Pain Inventory short form and the Defense and Veterans Pain Rating Scale). RESULTS:The overall rate of chronic pain was 68.2% in the 107 patients who completed the end point assessment. There was no significant effect of perioperative valproic acid administration, with a rate of 65.45% (N = 36) in the treatment group and a rate of 71.15% (N = 37) in the placebo group. Overall, pain scores decreased from baseline to follow-up (median = -2 on the numeric pain scale). Patients additionally experienced improvements in self-perceived function. CONCLUSIONS:The rate of chronic pain after amputation surgery is not significantly improved with the perioperative administration of valproic acid. In this cohort treated with multimodal perioperative analgesia and regional anesthetic blockade, we observed improvements in both pain severity and function.