Recap of UMB Confronts Chronic Pain Community Discussion in Baltimore
The University of Maryland, Baltimore (UMB) held a forum in Baltimore on June 19 to share the work being conducted across disciplines to better understand, treat, and modify the impact of chronic pain. The Community Conversation, held at The Radisson at Cross Keys, was moderated by Joel Greenspan, PhD, co-director of the UMB Center to Advance Chronic Pain Research (CACPR). Greenspan, professor and chair of the University of Maryland School of Dentistry (UMSOD) Department of Neural and Pain Sciences, characterized chronic pain as a complex problem affecting the quality of life of millions of U.S. residents who are kept from doing the things they need or want to do. “We’ve got a wide swath of talent,” he said, referring to UMB’s top-tier scientists and clinicians, adding that a "large constellation" is needed to gain traction.

Describing their efforts were CACPR members and panelists Asaf Keller, PhD, professor at the University of Maryland School of Medicine (UMSOM); Diane Hoffmann, JD, MS, director of the Law and Health Care Program and Jacob A. France Professor of Health Care Law at the Francis King Carey School of Law; Marcela Romero-Reyes, DDS, PhD, clinical associate professor at UMSOD and clinical director of its Brotman Facial Pain Clinic; and Luana Colloca, MD, PhD, MS, associate professor at the University of Maryland School of Nursing and associate professor at UMSOM. The event also gave guests a chance to try virtual or blended reality at a demonstration table set up by Colloca’s lab; her work is part of an initiative of the University of Maryland Strategic Partnership: MPowering the State.

During a question-and-answer session, guests shared observations and problems of their own or of family members who struggle with chronic pain. UMB’s Office of Philanthropy sponsored the forum, and Chief Philanthropy Officer and Vice President Thomas J. Sullivan, CFRE, MS, served as host. He described the leadership of UMB in the field of chronic pain, which encompasses afflictions such as low back pain, severe headaches or migraines, neck pain, facial and jaw pain, cancer-related pain, and bodily pain of unknown origin. UMB has been an epicenter of robust chronic pain research for many years and in 2014 established CACPR to build on its multidisciplinary pain research and expand innovative collaborations across the University.
Second International Society for Interdisciplinary Placebo Studies (SIPS)   Conference Brings Attention to Research, Clinical, and Societal Potential of Placebo Studies
The second official Society for Interdisciplinary Placebo Studies (SIPS) conference on placebo studies was held in Leiden, the Netherlands on July 7 to July 9 and hosted by the University of Leiden.

The beautiful historic Stadsegehoorzaal in Leiden has been a place of gathering and information exchange for artists, politicians and academicians since its construction in the early 1800s. Nestled into the narrow streets alongside some of Leiden’s quotidian cafés and shops, it is a natural place for community engagement and intellectual discourse. For its first two congregations, the Society for Interdisciplinary Placebo Studies has created its own interdisciplinary space here for scientists working on placebo from all around the globe to gather and discuss their medical, psychosocial, philosophical and neurobiological research. 

This year, the 2nd SIPS Conference began with a community-based event at the neighboring Rijksmuseum Boerhaave, which featured a public lecture about placebo and art alongside a public demonstration of placebo response in the laboratory setting. Keynote speakers included Jet Bussemaker, President of the Dutch Council for Public Health and Society, Irving Kirsch, director of the Program in Placebo Studies at Harvard Medical School, Ionica Smeets, Professor of Communication at Leiden University, and the University of Maryland’s own faculty Luana Colloca, all of whom addressed topics ranging from public policy to hypnosis, from health news in the media to virtual reality. Plenary sessions organized attendees into special interests to encourage networking, covering vast clinical, research and methodological topics and future directions of the field. 

Over the past four years, the two International Conference of The Society for Interdisciplinary Placebo Studies in 2017 and 2019 has attracted 317 and 301 participants, and included 102 and 100 podium presentations and 93 and 113 poster presentations by senior and junior scientists, respectively. From Colloca's lab, Elizabeth Olson, medical student and PRISM scholar, and Dr. Yang Wang, post-doctoral student, (pictured above respectively on the left and right, with Colloca in between), presented posters on sex differences and chronic orofacial pain as well as neural mechanisms underlying pain and analgesia shaped by observation.

We hope to host the 2021 SIPS conference at the University of Maryland and bring the vibrant and collegial community of scientists on pain modulation, placebo mechanisms and translational aspects.
Cynthia L. Renn, PhD, RN, FAAN
Dr. Cynthia Renn , in collaboration with MPIs Dr. Dorsey and Dr. Griffioen , was recently awarded a 5-year R01 to study the transition from acute to chronic pain in trauma patients with lower extremity fractures. This study will carefully phenotype patients over two years following their trauma event using quantitative sensory testing, a battery of self-report questionnaires, and RNA sequencing of peripheral blood. The study is currently recruiting and enrolling participants. In June, Dr. Renn and her collaborator MPI Dr. Coksaygan received a 1-year Accelerated Translational Incubator Pilot grant from the UMB Institute for Clinical & Translational Research to study the effects of a topical AT1R antagonist on wound healing and pain in a porcine diabetic foot ulcer model. This study is proceeding well after establishing the model and the pain testing methods.
About Cynthia Renn

The focus of my program of research is to identify new therapeutic targets that could lead to new treatment strategies for managing chronic pain. In my work, I design experiments to increase our understanding of the physiological mechanisms that underlie the development and persistence of chronic pain. I have had a career long focus on the physiological mechanisms of chronic pain and its treatment  that  stems from  my  years of clinical practice in emergency nursing and was heightened during my pre-doctoral training in the laboratory of Dr. Ronald Dubner. My program of research focuses on the pharmacological, cellular, biochemical, molecular biological, and genetic mechanisms that underlie the development and persistence of inflammatory, aromatase inhibitor-induced, chemotherapy-induced, nerve injury-induced, and post spinal cord injury chronic pain and the associated behavioral responses in rodent models of these conditions.

Recently, my research expertise has expanded to include clinical studies of experimental and chronic pain. I was an MPI on a P30­-funded project to study the genetic underpinnings of behavioral responses to acute experimental pain in Old Order Amish adults and I have been a co-I on several clinical studies examining the development of chemotherapy-induced peripheral neuropathy or aromatase inhibitor-induced arthralgia. I am currently an MPI of the P30-funded Omics Associated with Self-management Interventions for Symptoms (OASIS) Center and an R01 examining the transition from acute to chronic pain in trauma patients with lower extremity fractures. I was also the sponsor of an F31 NRSA that examined acute pain trajectories during hospitalization and chronic pain after discharge in trauma patients with lower extremity fractures. Each of these clinical studies involves psychometric and quantitative sensory testing of pain.

Overall, my work seeks to understand the mechanisms that underlie the development and  persistence of chronic pain to gain insight into human pathological pain conditions  and  identify new therapeutic  strategies. My projects provide exceptional opportunities to gain vital insight into the physiological, psychological, and genomic profiles of chronic pain patients and healthy subjects. The overarching goal is to find ways to improve pain management and quality of life for chronic pain patients.
Recent Publications
Colloca, Luana

Belcher AM, Cole TO, Greenblatt AD, Hoag SW, Epstein DH, Wagner M, Billing AS,
Massey E, Hamilton KR, Kozak ZK, Welsh CJ, Weintraub E, Wickwire EM, Wish ED,
Kaptchuk TJ, Colloca L. Open-label dose-extending placebos for opioid use disorder: a protocol for a randomised controlled clinical trial with methadone treatment. BMJ Open . 2019 Jun 21;9(6):e026604. doi: 10.1136/bmjopen-2018-026604. PubMed PMID: 31230007; PubMed Central PMCID: PMC6596949.
Duarte RV, McNicol E, Colloca L, Taylor RS, North RB, Eldabe S. Randomized Placebo-/Sham-Controlled Trials of Spinal Cord Stimulation: A Systematic Review and Methodological Appraisal. Neuromodulation . 2019 Jul 15. doi: 10.1111/ner.13018. [Epub ahead of print] Review. PubMed PMID: 31305001.
Akintola T, Tricou C, Raver C, Castro A, Colloca L, Keller A. In search of a rodent model of placebo analgesia in chronic orofacial neuropathic pain. Neurobiol Pain . 2019 May 14;6:100033. doi: 10.1016/j.ynpai.2019.100033. eCollection 2019 Aug-Dec. PubMed PMID: 31223137; PubMed Central PMCID: PMC6565753.

Colloca L, Schenk LA, Nathan DE, Robinson O, Grillon C. When therapeutic expectancies are violated: An fMRI study. Clin Pharmacol Ther . 2019 Jul 27. doi: 10.1002/cpt.1587. [Epub ahead of print] PubMed PMID: 31350784.
Greenspan, Joel D. 

Slade GD, Rosen JD, Ohrbach R, Greenspan JD, Fillingim RB, Parisien M, Khoury S, Diatchenko L, Maixner W, Bair E, Anatomical selectivity in overlap of chronic facial and bodily pain.  PAIN Reports. May/June 2019;4(3): e729.

  • This study examined the degree of overlap between chronic facial pain and pain reported a other body sites. In both univariate multivariable analyses, facial pain had greatest overlap with headache, followed by neck pain, whereas overlap decreased substantially for pain at successively remote locations below the neck. Findings were replicated in the UK Biobank study and the US National Health Interview Survey. The observed anatomical selectivity in the degree of overlap could be a consequence of neurosensory and/or affective processes that differentially amplify pain according to its location.

Meloto CB, Slade GD, Lichtenwalter RN, Bair E, Rathnayaka N, Diatchenko L, Greenspan JD, Maixner W, Fillingim RB, Ohrbach R. Clinical predictors of persistent temporomandibular disorder in people with first-onset temporomandibular disorder: A prospective case-control study.  J Am Dent Assoc . 2019 Jul;150(7):572-581.e10. PMID: 31248483.

  • The authors aimed to develop a predictive model of painful temporomandibular disorder (TMD) prognosis by using biopsychosocial measures from the Diagnostic Criteria for Temporomandibular Disorders (DC-TMD). Clinical measures that clinicians can assess readily when TMD first develops were found to be useful in predicting the risk of developing persistent TMD. Psychosocial measures are important predictors of onset but do not add meaningfully to the predictive capacity of clinical measures.

Khoury S, Piltonen MH, Ton AT, Cole T, Samoshkin A, Smith SB, Belfer I, Slade GD, Fillingim RB, Greenspan JD, Ohrbach R, Maixner W, Neely GG, Serohijos AWR, Diatchenko L. A functional substitution in the L-aromatic amino acid decarboxylase enzyme worsens somatic symptoms via a serotonergic pathway.  Ann Neurol . 2019 Aug;86(2):168-180. doi: 10.1002/ana.25521. Epub 2019 Jun 8. PMID: 31177555.

  • Using functional genomics approaches, this study identified a polymorphism in the L-aromatic amino acid decarboxylase (AADC) enzyme that contributes to somatic symptoms through reduced levels of 5-HT. Our findings suggest a molecular mechanism underlying the pathophysiology of multiply occurring somatic symptoms and opens new treatment options targeting the serotonergic system.
Resnick, Barbara

Resnick, B., Kolanowski, A., Van Haitsma, K., Galik, E., Boltz, M., Ellis, J., Behrens L., Eshragi, K., Viviano, N., Madrigal, C. Reliability and Validity of the Knowledge of Person-Centered Behavioral Approaches for BPSD Test.  Journal of Nursing Measurement . In press.   

Resnick B, Boltz M, Galik E, Holmes S, Vigne E, Fix S, Zhu S. The Impact of Function Focused Care and Physical Activity on Falls in Assisted Living Residents.  The Canadian Journal of Nursing Research . In press. 
Seminowicz, David A.

Corticomotor excitability reduction induced by experimental pain remains unaffected by performing a working memory task as compared to staying at rest. Larsen DB, Graven-Nielsen T, Hirata RP, Seminowicz D, Schabrun S, Boudreau SA. Exp Brain Res . 2019 Jun 19. doi: 10.1007/s00221-019-05587-y. [Epub ahead of print] PMID: 31218369
Corticomotor Depression is Associated With Higher Pain Severity in the Transition to Sustained Pain: A Longitudinal Exploratory Study of Individual Differences. Seminowicz DA, Thapa T, Schabrun SM. J Pain . 2019 Jun 13. pii: S1526-5900(19)30744-8. doi: 10.1016/j.jpain.2019.06.005. [Epub ahead of print] PMID: 31201993
Wu, Junfang 

Li Y, Jones JW, M C Choi H, Sarkar C, Kane MA, Koh EY, Lipinski MM, Wu J. cPLA2 activation contributes to lysosomal defects leading to impairment of autophagy after spinal cord injury.  Cell Death & Disease , 10(7):531. PMID: 31296844.

Wu J and Lipinski MM. Autophagy in neurotrauma: good or bad or dysregulated.  Cells , 2019, 8(7). pii: E693. PMID: 31295858.
Recent Presentations
Simon Akerman – Presentation ‘Neuronal PAC1 Receptors Mediate Delayed Activation and Sensitization of Trigeminocervical Neurons: Relevance to Migraine’. 61st American Headache Society meeting, July 11 to 14, 2019, Philadelphia, PA.

Dr. Luana Colloca presented at these meetings:
  • Ethics of placebos and placebo effects. Plenary Lecture 2019 XI Mexican Pain Forum. Mexico City, Mexico, June 7, 2019 (60 min) 
  • Observe to get better: neurobiological mechanisms of observationally-induced hypoalgesia. Invited Lecture at the National Center for Complementary and Integrative Health (NCCIH), Mind-Body series, Bethesda, MD, United States (60 min).
  • Mechanisms of observationally-induced pain modulation: from placebo effects to virtual reality. Keynote Lecture 2019 2nd official Society for Interdisciplinary Placebo Studies (SIPS) conference on placebo studies. Leiden, Netherlands. July 7, 2019 (60 min).
  • Mechanisms of observationally-induced placebo hypoalgesia. 2019 Mexican Pain Forum, Mexico City, Mexico, June 7, 2019 (45 min).

Marcela Romero-Reyes – Lecturer and organizer with Procedural Headache Medicine Section of the AHS. Pre-course “The Anatomy of Headache and Orofacial Pain: An Interventional Based Cadaver Course”. 61st Annual American Headache Society Scientific Meeting at the Pennsylvania Convention Center from July 11 to 14, 2019.
Dr. Junfang Wu presented the following papers at these meetings:
  • “The Function of Microglia in Spinal Cord Injury-Mediated Brain Neuroinflammation” in NIH Neuron-Glia Interactions Special Interest Group. Bethesda, MD. June 13, 2019.
  • “Microglia in Spinal Cord Injury-Mediated Brain Dysfunction” in The 2019 Glia and Neuroimmune Symposium. Guangzhou, China, August 2-3, 2019.
Recent Grant and Contract Awards
Barbara Resnick, PhD, RN, CRNP, FAAN, FAANP,  received a Helen and Leonard Stulman Foundation Grant to implement FFC-AL-EIT-D in assisted living facilities. 

David A. Seminowicz, PhD
R61 AT010134-01 (Seminowicz, MPI Finan)
Award Amount: $2,086,549
Separate and Combined Effects of Mindfulness Meditation and Savoring on Pain-Related Corticostriatal Function
The purpose of the proposed R61/R33 application is to determine and optimize the neural mechanisms supporting mindfulness-based pain relief in rheumatoid arthritis patients.
Special Acknowledgements
Between June and July 2019, as part of Vinita Agarwal ’s internal (competitive) Building Research Excellence (BRE) grant awarded by the Office of Graduate Studies and Research, Salisbury University, she completed her Vipassana meditation retreat at Vipassana International Academy, Igatpuri, Nasik, Maharashtra, India to understand mind-body relationship in healing experientially, and completed a course in Advanced Ayurvedic Diet and Nutrition from the International Academy of Ayurved, Pune, India. Both inform her book manuscript underway on “Healing Communication: A Relational Approach” (working title, Lexington Books), and study data gathering on Indian Ayurvedic physicians’ treatment philosophy and principles in chronic pain management. The study supports data gathered as part of the same BRE grant on US-based CAM providers’ approach in breast cancer survivorship management. To learn more, please visit:   

Marcela Romero-Reyes , Chair of the Special Interest Section of TMD, Cervical Spine and Orofacial pain of the American Headache Society participated in a lecture, "Temporomandibular Disorders: Diagnosis and Management" on July 11 th  during the 61 st  Annual Scientific Meeting of the American Headache Society. This pre-course was developed in collaboration with the Chair of the Special Section of Procedural Headache Medicine, Dr. Paul Mathew (Neurology/Harvard).
The UM Center to Advance Chronic Pain Research (CACPR) is a multidisciplinary center composed of nationally and internationally renowned clinical and preclinical translational scientists whose principle research focus is on the physiological, genetic, and psychosocial underpinnings of the development and persistence of debilitating chronic pain conditions.