Our lab is currently studying the biological mechanisms underlying the human response to nerve injury and surgery, in particular, the way injury induced neuroplasticity and inflammation often combine to cause chronic pain after surgery or trauma. We are using a systems biology approach to understand the molecular mechanisms of inflammation, focusing on nerve injury, chronic post-surgical pain, and the maladaptive processes involved in the transition from acute to chronic pain.  We utilize reverse translational methodology, identifying pathways and targets of interest in human case-control studies, and subsequently validating those findings with animal models of nerve injury.  This process focuses our research and improves our ability to discern clinically meaningful targets and future potential therapies.

We have grant support from several sources, including the DOD grants: “Regional Anesthesia and Valproate Sodium for the Prevention of Chronic Post-Amputation Pain” and “VIPER: Chronic Pain after Amputation: Inflammatory Mechanisms, Novel Analgesic Pathways, and Improved Patient Safety.” The regional anesthesia and valproate sodium trial employs a clinical trial, nested epigenomics and gene expression analysis to dissect mechanisms that may prevent the development of chronic pain. The VIPER inflammatory mechanisms grant explores pathways identified from molecular analysis of amputee biosamples utilizing animal modeling, cell culture, and cohort validation to determine whether these pathways may provide novel analgesic targets. In addition this grant funds an effort to identify patients at risk for opioid related adverse events. Our research group has additionally partnered with collaborators at the Defense & Veterans Center for Integrative Pain Management (DVCIPM) who conduct their research at Walter Reed National Military Medical Center for clinical trials that include both active duty and veteran amputee patients.

• In 2015, Thomas Van de Ven, MD, PhD, received a 3-year, $1.5 million Department of Defense (DoD) Neurosensory Research grant renewal for his VIPER (Veterans Integrated Pain Evaluation Research) study entitled “Chronic Pain after Amputation: Inflammatory Mechanisms, Novel Analgesic Pathways, and Improved Patient Safety.” Other personnel involved in this study are LTC Dr. Chester Buckenmaier, Associate Professor at Uniformed Services University of the Health Sciences, and Dr. Andrew Shaw, former Duke faculty and now Division Chief of Cardiothoracic Anesthesiology at Vanderbilt University Medical Center.
• Alexander Chamessian is the 1^st place receipt of the 24th Annual Duke Anesthesiology Academic Evening’s Medical Student category, for his project titled “Optogenetic control of A-beta fibers using a novel VGLUT1-Channelrhodopsin-EYFP mouse.” Read more about Academic Evening here
• Thomas Van de Ven, MD, PhD, has been awarded a one-year, $9,036 voucher for his proposal entitled, “Transcriptional Profiling of Sciatic Nerve Samples from Traumatic Amputees.” The 2015 Spring Core Facility Voucher Program is a joint program with the School of Medicine (SOM), the Duke Translational Research Institute (DTRI) Pilot Program and the Office of the Provost to enable investigators’ access to services for exciting new studies that are not yet externally funded. Dr. Van de Ven will use the funds for RNA sequencing and Data Analysis at two SOM core facilities/shared resources.
• Thomas Buchheit, MD, received notice of award in 2012 of a $2.9 million Department of Defense Grant over 4 years to study the role of epigenetics in the transition from acute inflammatory pain to chronic neuropathic pain. The grant, PT110575, titled “Regional Anesthesia and Valproate Sodium for the Prevention of Chronic Post-Amputation Pain” uses a clinical trial and nested epigenomics and gene expression analysis to dissect mechanisms that may prevent the development of chronic pain.

VIPER: Chronic Pain after Amputation: Inflammatory Mechanisms, Novel Analgesic Pathways, and Improved Patient Safety.
Congressionally Directed Medical Research Program
Award $1,500,000

This project is designed to determine whether two novel putative analgesic pathways discovered using Human VIPER amputee exome sequencing and metabolomic data may be therapeutic targets using animal models of neuropathic pain, astrocyte culture and validation of the initial pathway discovery in a separate human amputee cohort. In addition, this study will investigate genetic markers of opioid related adverse events. The Uniformed Services University of the Health Sciences and Vanderbilt University Medical Center are additional study sites.

Regional Anesthesia and Valproate Sodium for the Prevention of Chronic Post-Amputation Pain
Congressionally Directed Medical Research Program Log # PT1100575.
Award: $2,870,989

In this research we are testing the efficacy of valproic acid and regional anesthesia in the prevention of chronic post-amputation pain. We are additionally elucidating the underlying epigenetic mechanisms involved in the transition of acute to chronic pain and the effect of therapies on DNA methylation patterns.

Reconsidering Addiction and Opioid Abuse: Is there a causal chain between opioid addiction, morbidity, and mortality?
Duke Institute for Brain Sciences Bass Connections Award, 2016-2017
Award $22,000

Perioperative Dexamethasone to Promote Systemic Pro-Resolution Phenotype for Prevention of Acute and Chronic Pain Post-Total Knee Arthroplasty.

This project studies the perioperative use of multiple dexamethasone dosing regimens before and after TKA, along with blood sample collection at multiple timepoints for macrophage phenotype analysis and plasma cytokine arrays.

Analysis of Gut Microbiota in Chronic Pain Patients.

This study involves microbiome analysis of patients with chronic overlapping pain conditions. It is being performed in collaboration with the company uBiome.

Effect of Thoracic Epidurals on the Incidence and Severity of Post-Thoracotomy Pain.

This study acts as a pilot project in anticipation of a larger therapeutic trial using DHA/EPA and their pro-resolution mediator metabolites to prevent chronic post-thoracotomy pain.

Past Studies

Molecular Signatures of Chronic Pain Subtypes
Department of Defense: 2011- 2014
Congressionally Directed Medical Research Program Log #DM102142
Award: $1,336,074

In this study, we analyzed metabolomics, proteomics, and gene expression in chronic pain. By correlating these alterations with clinical post-amputation phenotypes, we are currently utilizing these findings to identifying novel biomarkers of persistent neuropathic pain.

Veotria (Veda) Byrd, MPH
Clinical Research Coordinator II

Alex Chamessian

1. Kent ML, Hsia HLH, Van de Ven T, and Buchheit, TE. Perioperative Pain Management Strategies for Amputation: A Topical Review. Accepted for publication, June, 2016. Pain Medicine.
2. Buchheit, T, Van de Ven, T, John Hsia, HL, McDuffie, M, MacLeod, DB, White, W, Chamessian, A, Keefe, FJ, Buckenmaier, CT, and Shaw, AD. “Pain Phenotypes and Associated Clinical Risk Factors Following Traumatic Amputation: Results from Veterans Integrated Pain Evaluation Research (VIPER).” Pain medicine (Malden, Mass.) (July 14, 2015).
3. Mauck, M, Van de Ven, T, and Shaw, AD. “Epigenetics of chronic pain after thoracic surgery.” Curr Opin Anaesthesiol 27, no. 1 (February 2014): 1-5. (Review)
4. Van De Ven, T, and Ji, RR. “Dietary control of chronic headache: Involvement of pro-resolution lipid mediators.” Pain 154, no. 11 (November 1, 2013): 2247-2248.
5. Clarke, C, Lindsay, DR, Pyati, S, and Buchheit, T. “Residual limb pain is not a diagnosis: a proposed algorithm to classify postamputation pain.” Clin J Pain 29, no. 6 (June 2013): 551-562. (Review).
6. Buchheit, T, Van de Ven, T, and Shaw, A. “Epigenetics and the transition from acute to chronic pain.” Pain Med 13, no. 11 (November 2012): 1474-1490. (Review).
7. Van de Ven, TJ, and John Hsia, HL. “Causes and prevention of chronic postsurgical pain.” Curr Opin Crit Care 18, no. 4 (August 2012): 366-371. (Review).
8. Buchheit, T, and Pyati, S. “Prevention of chronic pain after surgical nerve injury: amputation and thoracotomy.” Surg Clin North Am 92, no. 2 (April 2012): 393-x. (Review).
9. Lindsay DR, Pyati S, Buchheit TE, Shaw A. Residual limb pain: more than a single entity? Anesthesiology. 2012 Jan;116(1):224; author reply 224-5.
10. Azari, P, Lindsay, DR, Briones, D, Clarke, C, Buchheit, T, and Pyati, S. “Efficacy and safety of ketamine in patients with complex regional pain syndrome: a systematic review.” CNS Drugs 26, no. 3 (March 1, 2012): 215-228. (Review).