Simon Haroutounian, PhD, MSc
Chief, Division of Clinical and Translational Research; Chief of Clinical Pain Research, Washington University Pain Center; Associate Professor
- Email: email@example.com
Dr. Harountounian’s research focus is on chronic pain. Pain is one of the leading causes of disability worldwide and is the single most common reason people seek medical care. While acute pain episodes are typically time-limited and can be treated reasonably well in most cases, chronic pain – which affects about 20% of the adult population – is largely undertreated. Especially challenging is neuropathic pain, a consequence of damage or disease affecting the central or the peripheral nervous systems.
Chronic pain may be related to concomitant medical conditions (e.g. diabetes, stroke, multiple sclerosis, or cancer), be of unknown origin, or be a result of treatment such as surgery or chemotherapy, that was aimed to cure a disease or improve the person’s quality of life.
It is an enormous and costly effort to match the right analgesic treatment (or combination of treatments) to the right patient – the therapy that will allow good pain relief and improved quality of life but will not cause side effects. Currently, this individual treatment “tailoring” is more of an art than a science.
By applying translational research, we explore methods to prevent chronic pain when possible, and to make the individualized pain management a science.
Dr. Haroutounian is Chief of the Division of Clinical and Translational Research (DoCTR), an Assistant Professor of Anesthesiology, and the Chief of Clinical Research at the Washington University Pain Center. Dr. Haroutounian has obtained his BSc.Pharm and MSc.Pharm degrees, as well as his PhD from The Hebrew University of Jerusalem. He has completed a Fulbright doctoral fellowship in pain outcomes research at the University of Utah (2008-2009, with Prof. Arthur G. Lipman), and a post-doctoral fellowship in clinical pain research at the Danish Pain Research Center in Aarhus, Denmark (2011-2013, with Prof Troels S. Jensen).
1. Understanding the individual clinically-relevant mechanisms involved in central and peripheral neuropathic pain.
Following peripheral nerve damage – molecular, morphological and functional changes occur not only in the injured nerve axon, but also in the cell body in the dorsal root ganglion, and within the CNS – particularly in the spinal cord dorsal horn. The combination of these peripheral and central changes (which is highly variable at the individual level) contributes to the ongoing pain and sensory changes that the patients experience. The central changes that lead to increased signal amplification at the spinal cord level and decreased descending pain modulation from supraspinal sites are termed “central sensitization” – a phenomenon that has been a subject of increased research and clinical interest recently. We have shown that central sensitization on its own does not generate or maintain chronic neuropathic pain (Haroutounian, 2014), and continue to investigate the individual characteristics that may shed light on the relative contribution of peripheral vs. central mechanisms in driving different types of neuropathic pain.
2. Undertaking pharmacokinetic and sensory phenotyping approach to predict individual response to pharmacotherapy in patients with chronic (predominantly neuropathic) pain.
We have a major interest in investigating individually tailored analgesic pharmacotherapy approaches. By using methodologies that include pharmacogenetics, pharmacokinetic analysis, morphological and functional nerve fiber assessment and psychological evaluation, we aim to identify predictors of individual response to pharmacological interventions in neuropathic pain arising from different conditions such as diabetic neuropathy, chemotherapy-induced peripheral neuropathy, and HIV sensory neuropathy.
3. Using patient-reported outcomes to guide interdisciplinary pain management in chronic pain.
Chronic pain detrimentally affects patients’ and their families’ quality of life and is associated with enormous costs. The interdisciplinary approach is considered the best currently available treatment option for chronic pain, as it is aimed to address the physical, emotional, and social disability associated with pain. However, there are several important limitations of interdisciplinary pain programs in their current format. One of these is the lack of sufficient tools to allow developing the treatment program around individual patients’ desires, expectations, and preferred outcomes.
An exciting area of research for us is to address what are the preferred study methodology and important outcomes from patients’ perspective and to investigate whether interdisciplinary care and decision-making guided by patient-reported physical, social and emotional disability associated with chronic pain (Haroutounian, 2012) improves treatment outcomes.
4. Investigating individual mechanisms, risk factors, and intervention methods to prevent chronic pain.
Persistent postsurgical pain (PPSP) is an undesired and a quite common consequence of many surgical procedures, such as amputations, thoracic and breast surgeries, and joint replacements. As an iatrogenic condition, it may be possible to reduce its incidence and severity, once we gain enough knowledge of the individual risk factors and mechanisms associated with PPSP. Some of our previous work have addressed the possible mechanisms (Haroutounian, 2013) and preventive approaches (McNicol, 2014), and we continue to learn about the epidemiology and to investigate novel approaches for possible prevention of PPSP.
Ongoing Clinical Trials
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- Haroutounian S, Ford AL, Frey K, Nikolajsen L, Finnerup NB, Neiner A, Kharasch ED, Karlsson P, Bottros M. “How central is central post-stroke pain? The role of afferent input in post-stroke neuropathic pain”. PAIN 2018 (in press). PubMed
- Hwang CT, Van Dillen LR, Haroutounian, S. “Do Changes in Sensory Processing Precede Low Back Pain Development in Healthy Individuals?” Clin J Pain 2018: 34(6). PubMed
- Meacham K, Shepherd A, Mohapatra DP, Haroutounian S. “Neuropathic Pain: Central vs. Peripheral Mechanisms”. Current Pain and Headache Reports. 2017; 21(6) PubMed
- Edwards RR, Dworkin RH, Turk DC, Angst MS, Dionne R, Freeman R, Hansson P, Haroutounian S, Arendt-Nielsen L, Attal N, Baron R, Brell J, Bujanover S, Burke LB, Carr D, Chappell AS, Cowan P, Etropolski M, Fillingim RB, Gewandter JS, Katz NP, Kopecky EA, Markman JD, Nomikos G, Porter L, Rappaport BA, Rice AS, Scavone JM, Scholz J, Simon LS, Smith SM, Tobias J, Tockarshewsky T, Veasley C, Versavel M, Wasan AD, Wen W, Yarnitsky D. “Patient phenotyping in clinical trials of chronic pain treatments: IMMPACT recommendations” PAIN 2016. PubMed
- McNicol ED, Ferguson MC, Haroutounian S, Carr DB, Schumann R. “Single dose intravenous paracetamol or intravenous propacetamol for postoperative pain” Cochrane Database of Systematic Reviews 2016 May 23;5. PubMed
- Finnerup NB, Haroutounian S, Kamerman P, Baron R, Bennett DL, Bouhassira D, Cruccu G, Freeman R, Hansson P, Nurmikko T, Raja SN, Rice AS, Serra J, Smith BH, Treede RD, Jensen TS. “Neuropathic pain: An updated grading system for research and clinical practice”. PAIN 2016 Jan 13. PubMed
- Ginosar Y, Haroutounian S, Kagan L, Naveh M, Aharon A, Davidson EM. “Proliposomal Ropivacaine Oil: Pharmacokinetic and Pharmacodynamic Data After Subcutaneous Administration in Volunteers”. Anesth Analg. 2016 May;122(5):1673-80. PubMed
- Davidson EM, Haroutounian S, Kagan L, Naveh M, Aharon A, Ginosar Y. “A Novel Proliposomal Ropivacaine Oil: Pharmacokinetic-Pharmacodynamic Studies After Subcutaneous Administration in Pigs”. Anesth Analg. 2016 May;122(5):1663-72. PubMed
- Haroutounian S, Ratz Y, Ginosar Y, Furmanov K, Saifi F, Meidan R, Davidson E. “The Effect of Medicinal Cannabis on Pain and Quality of Life Outcomes in Chronic Pain: A Prospective Open-label Study”. Clin J Pain. 2016 Feb 17. PDF
- Haroutounian S. “Somatosensory phenotyping for better translation in neuropathic pain?” PAIN 2016 May;157(5):995-6 PubMed
- Karlsson PR, Haroutounian S*, Polydefkis M, Nyengaard JR, Jensen TS. ”Structural and functional characterization of nerve fibres in polyneuropathy and healthy subjects”. Scandinavian Journal of Pain 10 (2016) 28–35 *equal first PDF
- Moore RA, Wiffen PJ, Eccleston C, Derry S, Baron R, Bell RF, Furlan AD, Gilron I, Haroutounian S, Katz NP, Lipman AG, Morley S, Peloso PM, Quessy SN, Seers K, Strassels SA, Straube S. “Systematic review of enriched-enrolment randomised-withdrawal trial designs in chronic pain: a new framework for design and reporting.”. Pain. 2015 Jan 28. [Epub ahead of print] PubMed
- Finnerup NB, Attal N, Haroutounian S, McNicol E, Baron R, Dworkin RH, Gilron I, Haanpää M, Hansson P, Jensen TS, Kamerman PR, Lund K, Moore A, Raja SN, Rice AS, Rowbotham M, Sena E, Siddall P, Smith BH, Wallace M. “Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis”. Lancet Neurol. 2015 Jan 6. [Epub ahead of print] PubMed
- Haroutounian S, Nikolajsen L, Finnerup NB, Jensen TS. “Topical Capsaicin Response as a Phenotypic Measure in Patients with Pain”. Pain Med. 2014 Dec 17. [Epub ahead of print] PubMed
- McNicol ED, Schumann R, Haroutounian S. “A Systematic Review and Meta-Analysis of Ketamine for the Prevention of Persistent Post-Surgical Pain”. Acta Anaesthesiologica Scandinavica 2014. Epub 2014 Jul 25. PubMed
- Haroutounian S, Nikolajsen L, Bendtsen TF, Finnerup NF, Kristensen AD, Hasselstrøm JB, Jensen TS. “Primary afferent input critical for maintaining spontaneous pain in peripheral neuropathy”. Pain 2014; 155(7):1272-1279. PDF
- Bendtsen TF, Pedersen EM, Haroutounian S, Søballe K, Moriggl B, Nikolajsen L, Hasselstrøm JB, Fisker AK, Strid JMC, Iversen, B M, Børglum J. “The Suprasacral Parallel Shift versus a Lumbar Plexus Blockade with Ultrasound-Guidance in Healthy Volunteers – a Randomized Controlled Trial”. Anaesthesia 2014 (in Press). PubMed
- Haroutiunian S, Kagan L, Yifrah-Damari I, Davidson E, Ratz Y, Hoffman A. “Similar systemic exposure and enhanced antinociceptive efficacy of epidural vs. intravenous methadone in a rat model” British Journal of Anaesthesia 2014; 112(1):150-8. PDF
- Nikolajsen L, Christensen KF, Haroutiunian S. “Phantom Limb Pain: Treatment Strategies”. Pain Management 2013; 3(6):421-424. PubMed
- Nikolajsen L, Haroutiunian S. “Adjuvant Effect of Oral Caffeine in Combination Analgesic Products for Acute Pain.” Danish Medical Bulletin 2013;42:2486-2488. PDF (Danish)
- Haroutiunian S, Nikolajsen L, Finnerup, NB, Jensen TS. “The neuropathic component in persistent postsurgical pain A Systematic Literature Review.” Pain 2013;154(1):95-102. PDF
- Haroutiunian S, Donaldson G, Yu J, Lipman AG. “Development and Validation of Shortened, Restructured Treatment Outcomes in Pain Survey Instrument (the S-TOPS) for Assessment of Individual Pain Patients’ Health-related Quality of Life.” Pain 2012;153(8):1593-601. PDF
- Haroutiunian S, McNicol E, Lipman AG. “Methadone for chronic noncancer pain”. Cochrane Database of Systematic Reviews 2012 Nov 14;11. PDF
- Nikolajsen L, Haroutiunian S. “Intravenous Patient-controlled Analgesia for Acute Postoperative Pain.” European Journal of Pain Supplements 2011; 5:453-456. PDF
- Kovo M, Wainstein J, Matas Z, Haroutiunian S, Hoffman A, Golan A. “Placental transfer of the insulin analog glargine in the ex-vivo perfused placental cotyledon model”. Endocrine Research 2011; 36(1):19-24. PubMed
- Ghate SR, Haroutiunian S, Winslow R, McAdam-Marx C. “Cost and Comorbidities Associated with Opioid Abuse in Managed Care and Medicaid Patients in the United States: A Comparison of Two Recently Published Studies.” Journal of Pain & Palliative Care Pharmacotherapy 2010; 24:251-258. PDF
- Haroutiunian S, Moshel S. “Preventing Drug-Related Problems: Integration of Clinical Pharmacists in the Caregivers’ Team.” Israeli Journal of Family Practice 2010; 20(159):23-27.
- Davidson E, Barenholz Y, Cohen R, Haroutiunian S, Kagan L, Ginosar, V. “High Dose Bupivacaine Remotely-loaded into Multivesicular Liposomes Demonstrates Slow Drug Release without Systemic Toxic Plasma Concentrations after Subcutaneous Administration in Humans.” Anesthesia and Analgesia 2010; 110(4):1018-23. PDF
- Haroutiunian S, Drennan DA, Lipman AG. “Topical NSAIDs Therapy for Musculoskeletal Pain.” Pain Medicine 2010; 11(4):535-49. PDF
- Haroutiunian S, Lecht S, Zur AA, Hoffman A, Davidson E. “The Challenge of Pain Management in Patients with Myasthenia Gravis.” Journal of Pain & Palliative Care Pharmacotherapy 2009; 23(3):242-60. PDF
- Haroutiunian S, Ratz Y, Rabinovitch B, Adam M, Hoffman A. “Valproic Acid Plasma Concentration Decrease in a Dose-independent Manner Following Administration of Meropenem – A Retrospective Study.” Journal of Clinical Pharmacology 2009; 49(11):1363-9. PDF
- Haroutiunian S, Rosen G, Shouval R, Davidson E. “Open-label, Add-on Study of Tetrahydrocannabinol for Chronic Nonmalignant Pain.” Journal of Pain & Palliative Care Pharmacotherapy 2008;22(3):213-7. PubMed
- Kovo M, Haroutiunian S*, Feldman N, Hoffman A, Glezerman M. “Determination of Metformin Transfer Across the Human Placenta Using a Dually Perfused ex vivo Placental Cotyledon Model.” European Journal of Obstetrics & Gynecology and Reproductive Biology 2008; 136(1):29-33. * equal first. PDF
- Lecht S, Haroutiunian S*, Hoffman A, Lazarovici P. “Rasagiline – A Novel MAO B Inhibitor in Parkinson’s Disease Therapy.” Therapeutics and Clinical Risk Management 2007; 3(3):467-474. * equal first PubMed