RELIEVING PAIN IN AMERICA
CACPR MEMBER SPOTLIGHT:
Marcela Romero Reyes, DDS, PhD and Simon Akerman, PhD
About Marcela Romero-Reyes

Dr. Marcela Romero-Reyes is a Clinical Associate Professor and the Clinical Director of The Brotman Facial Pain Clinic in the Department of Neural and Pain Sciences, School of Dentistry. In addition, Dr. Romero-Reyes is Chair of the Special Interest Section of TMD, Cervical Spine and Orofacial Pain of the American Headache Society .

Dr. Romero-Reyes is a clinician scientist with a broad background in basic sciences including immunology and neuroscience, and specialty clinical training in the management of orofacial pain (OFP) disorders, including trigeminal neuropathies, temporomandibular disorders (TMD), and primary headache disorders. The focus of her work is translational and from this perspective she is able to see first-hand the needs of the OFP and headache sufferer, not only as a care provider, but also how these needs can be solved and explored at the bench side. 
About Simon Akerman

Dr. Simon Akerman is an Assistant Research Professor in the Department of Neural and Pain Sciences, School of Dentistry. Dr. Akerman has a broad background in neurological sciences, but specifically more than 20 years of experience studying basic mechanisms related to headache disorders, including migraine and trigeminal autonomic cephalalgias. His laboratory has extensive expertise in  in vivo  electrophysiology and neurovascular physiology. He has developed several unique animal models of headache, specifically, the only validated model of trigeminal autonomic cephalalgias. He has been a regular invited speaker at international and national headache meetings for the last 15 years, as well as a member of the scientific advisory/program committees for these meetings.
Investigating the Pathophysiology of Debilitating Pain

Some of the most debilitating pain disorders arise from the trigeminal system. Orofacial Pain (OFP) disorders involve musculoskeletal disorders known as temporomandibular disorders (TMD), neuropathic pain disorders including trigeminal neuralgia and other craniofacial neuropathies. These also cover neurovascular disorders, such as primary headache disorders, including migraine, the most prevalent and debilitating of all the neurological disorders, and trigeminal autonomic cephalalgias, such as cluster headache, reported as the cause of the most extreme pain.  

In the main, Dr. Romero and Dr. Akerman’s laboratories share an integrated focus to better understand the pathophysiology of these pain disorders, with the use of unique pre-clinical models (Refs 1, 4, 9, 10) using a multidisciplinary approach, combining electrophysiology, neurovascular physiology, conscious behavioral approaches, as well as molecular biology and pharmacology. Their primary goal is to elucidate mechanisms related to these disorders and dissecting and validating novel targets, for safe and more effective management that improve the quality of life of the orofacial pain and headache sufferer. 

Recent projects include dissecting the important role of calcitonin gene-related peptide (CGRP) in TMDs (Ref 6), led by Dr. Romero, using a novel behavioral approach to study spontaneous pain in the craniofacial region. We have also validated the use of cervical vagus nerve stimulation for the treatment of episodic migraine and cluster headache (led by Dr. Akerman, Ref 5), data that was used to support its FDA approval, as well as validating a preclinical model of migraine using current migraine preventives (Ref 4). In our most recent work led by Dr. Akerman, in collaboration with the Goadsby group in the UK, we have translated the novel clinical findings that the experimental migraine trigger, nitroglycerin, provokes migraine associated allodynia, and this is mediated by activation and sensitization and central trigeminovascular pathways (Ref 1). This represents a unique opportunity to study allodynia in patients that translates preclinically, allowing us to better understand the mechanisms of treatments. 

Ongoing research continues these themes, focusing on the role of neuroinflammatory and nitroxidative mechanisms in the development of trigeminal neuropathic pain (Romero) and headache (Romero and Akerman) disorders. Further, the collaboration of our laboratories places us in the unique position to the study the co-morbidity between TMD and headache disorders. Features include, when either is present they can increase the likelihood, and exacerbate the presence, of the other. We are also dissecting novel pharmacologies which link these pain disorders, with the strong hope of identifying new treatment targets for their management. With the addition of behavioral methodologies provided by Dr. Romero’s laboratory, Dr. Akerman is also continuing research into the role of pituitary adenylate pituitary adenylate cyclase activating peptides (PACAP) and the PAC1 receptor in mechanisms related to migraine and cluster headache (Ref 8). These current studies are focusing on the role of the cranial parasympathetic projection in mediating nocifensive behaviors, and how activation of this pathway, release of PACAP and activation of PACAP receptors, is crucial to the development and maintenance of the severe and prolonged headache in these disorders.

Recent and most relevant publications:

  1. S Akerman, N Karsan, P Bose P, JR Hoffmann, M Romero-Reyes and PJ Goadsby (2019) Nitroglycerine triggers triptan-responsive cranial allodynia and trigeminal neuronal hypersensitivity. Brain 142: 103-19. 
  2. M Vila-Pueyo, J Hoffmann, M Romero-ReyesS Akerman (2018) Brain structure and function related to headache: Brainstem structure and function in headache. Cephalalgia. 2018:333102418784698. doi: 10.1177/0333102418784698. [Epub ahead of print] PubMed PMID: 29969040.
  3. S AkermanM Romero-Reyes, PR Holland (2017) Current and novel insights into the neurophysiology of migraine and its implications for therapeutics. Pharmacol Ther. 172:151-170. 
  4. S Akermanand M Romero-Reyes (2017) Targeting the central projection of the dural trigeminovascular system for migraine prophylaxis J Cereb Blood Flow Metab 271678X17729280.
  5. S Akerman, B Simon and M Romero-Reyes (2017) Vagus nerve stimulation suppresses acute noxious activation of trigeminocervical neurons in animal models of primary headache Neurobiol Dis 102: 96-104. 
  6. M Romero-Reyes, V Pardi and S Akerman (2015) A potent and selective calcitonin gene-related peptide (CGRP) receptor antagonist, MK-8825, inhibits responses to nociceptive trigeminal activation: Role of CGRP in orofacial pain. Exp Neurol 271: 95-103. 
  7. M Romero-Reyes,A. Teruel, and Y. Ye (2015) Cancer and Referred Facial Pain. Current Pain and Headache Reports 19(8): p. 1-9. 
  8. S Akermanand PJ Goadsby (2015) Neuronal PAC1 receptors mediate delayed activation and sensitization of trigeminocervical neurons: Relevance to migraine. Sci Trans Med. 7:308ra157.
  9. M Romero-ReyesS Akerman, E Nguyen, A Vijjeswarapu, B Hom, HW Dong, A Charles (2013) Spontaneous Behavioral Responses in the Orofacial Region: A model of Trigeminal Pain in Mouse. Headache: The Journal of Head and Face Pain. 53(1):137-51.
  10. S Akerman, PR Holland, O Summ, MP Lasalandra and PJ Goadsby (2012) A translational in vivo model of trigeminal autonomic cephalalgias – therapeutic characterization. Brain 135:3664-75.


Recent and upcoming presentations:

  • M Romero-Reyes- Moderator/presenter ‘Painful Posttraumatic Trigeminal Neuropathy’. Eastern Pain Association, EPA 2019 Spring Meeting, Saturday, April 13, 2019, SUNY Global Center.
  • M Romero-Reyes- Lecture ‘Translational Perspectives in Orofacial Pain and Headache’. Eastman Institute for Oral Health, Rochester NY, April 27, 2019.
  • M Romero-Reyes- Lecture ‘Translational Perspectives for the standard of care in Orofacial Pain and Headache: The role of integrative and complementary medicine’ Acupuncture and Integrative Oral Medicine Course. UCLA East West Health Center, May 17, 2019.
  • S Akerman – Seminar ‘PACAP and its receptors in nervous system’. 13th European Headache Federation Congress, May 29 to June 2, 2019, Athens, Greece. 
  • M 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 on July 11 to 14, 2019.
  • S Akerman– Presentation ‘Neuronal PAC1 Receptors Mediate Delayed Activation and Sensitization of Trigeminocervical Neurons: Relevance to Migraine’. 61stAmerican Headache Society meeting, July 11 to 14, 2019, Philadelphia, PA.
  • M Romero-Reyes- Lecture, ‘Differential diagnosis and treatment of temporomandibular disorders and trigeminal neuralgia’, 19th Congress of the International Headache Society, September 5 to 8, 2019, Dublin Ireland.
  • S Akerman– Seminar ‘Non-invasive neuromodulators role in the treatment of migraine and cluster headache: do they work and how – vagus nerve stimulation’. 19th Congress of the International Headache Society. September 5 to 8, 2019, Dublin, Ireland.
Recent Publications, Presentations, and Grant and Contract Awards by CACPR Members
Agarwal, Vinita
 
Agarwal, V. (2019).  Patient communication of chronic pain in the complementary and alternative medicine therapeutic relationship . 69 th Annual International Communication Association (ICA) Conference. Washington D.C. May 24–28, 2019.
Burrowes, Shana

Brain Imaging Behav. 2019 Apr 12. doi: 10.1007/s11682-019-00095-7. [Epub ahead of print] Decreased grey matter volume in mTBI patients with post-traumatic headache compared to headache-free mTBI patients and healthy controls: a longitudinal MRI study.
Burrowes SAB 1,2,3 Rhodes CS 4 Meeker TJ 2 Greenspan JD 2,3 Gullapalli RP 4 Seminowicz DA 5,6 .
Cloeren, Marianne
 
New CACPR member Marianne Cloeren, MD, MPH, from the School of Medicine Division of Occupational and Environmental Medicine, was recently awarded two grants to support an interdisciplinary multiphase project called Operation PROSPER: Peer Reintegration and Other Services Promoting Employment in Recovery. With co-PI Dr. Jodi Jacobsen Frey from the School of Social Work, this project will address the risks for work disability in patients treated with Medication Assisted Treatment for Opioid Use Disorder in UMB clinics. Among these risks are chronic pain, symptom catastrophizing and disability beliefs. In later phases, the team will pilot interventions to mitigate these risks and support engagement in work. The two grants are the Accelerated Translational Incubator Pilot (ATIP) Award from the UMB Institute for Clinical and Translational Research (ICTR) and the Center for Addition Research, Education, and Service (CARES) Science to Systems Grant (SSG) program.
Colloca, Luana

Goo SJ, Frangos E, Richards EA, Ceko M, Justement BL, Korb P, Walitt BT,
Colloca L, Bushnell MC. Attitudes and Perceptions Toward Authorized Deception: A 
Pilot Comparison of Healthy Controls and Fibromyalgia Patients. Pain Med. 2019
Apr 22. pii: pnz081. doi: 10.1093/pm/pnz081. [Epub ahead of print] PubMed PMID:
31009537.

Colloca L, Wang Y, Martinez PE, Christy Chang YP, Ryan KA, Hodgkinson C,
Goldman D, Dorsey SG. OPRM1 rs1799971 - COMT rs4680 - FAAH rs324420 genes
interact with placebo procedures to induce hypoalgesia. Pain. 2019 May 6. doi:
10.1097/j.pain.0000000000001578. [Epub ahead of print] PubMed PMID: 30985623.

Palese A, Cadorin L, Testa M, Geri T, Colloca L, Rossettini G. Contextual
factors triggering placebo and nocebo effects in nursing practice: Findings from 
a national cross-sectional study. J Clin Nurs. 2019 May;28(9-10):1966-1978. doi: 
10.1111/jocn.14809. Epub 2019 Feb 18. PubMed PMID: 30706543.
Dorsey, Susan
 
PLoS One. 2019 May 16;14(5):e0216539. doi: 10.1371/journal.pone.0216539. eCollection 2019.
Whole blood transcriptomic profiles can differentiate vulnerability to chronic low back pain.
Dorsey SG 1 Renn CL 1 Griffioen M 2 Lassiter CB 3 Zhu S 1 Huot-Creasy H 4 McCracken C 4 Mahurkar A 4 Shetty AC 4 Jackson-Cook CK 5 Kim H 6 Henderson WA 6 Saligan L 6 Gill J 6 Colloca L 1 Lyon DE 7 Starkweather AR 8 .

Semin Oncol Nurs. 2019 May 10. pii: S0749-2081(19)30059-2. doi: 10.1016/j.soncn.2019.04.011. [Epub ahead of print]
Genetic Variants Associated with Cancer Pain and Response to Opioid Analgesics: Implications for Precision Pain Management.
Yang GS 1 Barnes NM 2 Lyon DE 2 Dorsey SG 3 .

PLoS One. 2019 Apr 18;14(4):e0215534. doi: 10.1371/journal.pone.0215534. eCollection 2019.
Racial/ethnic differences in experimental pain sensitivity and associated factors - Cardiovascular responsiveness and psychological status.
Kim HJ 1 Greenspan JD 2 Ohrbach R 3 Fillingim RB 4 Maixner W 5 Renn CL 6 Johantgen M 7 Zhu S 7 Dorsey SG 6 .
Faden, Alan

Presentations: University of Maryland SOM, Neurosurgery Grand Rounds, April 11, 2019; IARS Panel, Montreal, Canada, May 17, 2019

Grants:

PA-18-484,NINDS                  Faden, Wu (MPI)                                                        04/01/2019-03/31/2024
Mechanism of Inflammatory Related Brain Dysfunction after Spinal Cord Injury
Examines mechanisms of SCI-mediated dementia and therapeutic interventions in rodent model of SCI.

PA-18-484,NINDS                  Loane, Faden, Stoica (MPI)                                        04/01/2019-03/31/2024
Reprogramming Microglial Epigenetic Pathways to Promote Cognitive Recovery after Brain Trauma
Examines potential role of pathological epigenetic mechanisms in promoting chronic neurotoxic microglial

Publications:

Ritzel RM, Doran SJ, Glaser EP, Meadows VE, Faden AI, Stoica BA, Loane DJ. Old Age Increases Microglial Senescence, Exacerbates Secondary Neuroinflammation, And Worsens Neurological Outcomes After Acute Traumatic Brain Injury In Mice.  Neurobiol Aging. 2019 May;77:194-206. Epub 2019 Feb 20. PMID: 30904769

Doran SJ, Ritzel RM, Glaser EP,Henry RJ, Faden AI, Loane DJ. Sex Differences in Acute Neuroinflammation after Experimental Traumatic Brain Injury Are Mediated by Infiltrating Myeloid Cells.  J Neurotrauma . 2019 Apr 1;36(7):1040-1053. Epub 2018 Nov 16. PMID:30259790
Melemedjian, Ohannes
 
Ludman T, Melemedjian OK. Bortezomib-induced aerobic glycolysis contributes to chemotherapy-induced painful peripheral neuropathy. Mol Pain. 2019 Jan-Dec;15:1744806919837429. doi: 10.1177/1744806919837429. PubMed PMID: 30810076; PubMed Central PMCID: PMC6452581.

Ludman T, Melemedjian OK. Bortezomib and metformin opposingly regulate the expression of hypoxia-inducible factor alpha and the consequent development of chemotherapy-induced painful peripheral neuropathy. Mol Pain. 2019 Jan-Dec;15:1744806919850043. doi: 10.1177/1744806919850043. PubMed PMID: 31041875; PubMed Central PMCID: PMC6509977.
Seminowicz, David
 

Da Silva JT, Letzen JE, Haythornthwaite JA, Finan PH, Campbell CM, Seminowicz
DA. Do chronic pain and comorbidities affect brain function in sickle cell
patients? A systematic review of neuroimaging and treatment approaches. Pain.
2019 Apr 24. doi: 10.1097/j.pain.0000000000001591. [Epub ahead of print] PubMed
PMID: 31045749.

Burrowes SAB, Rhodes CS, Meeker TJ, Greenspan JD, Gullapalli RP, Seminowicz
DA. Decreased grey matter volume in mTBI patients with post-traumatic headache
compared to headache-free mTBI patients and healthy controls: a longitudinal MRI
study. Brain Imaging Behav. 2019 Apr 12. doi: 10.1007/s11682-019-00095-7. [Epub
ahead of print] PubMed PMID: 30980274.

Krimmel SR, White MG, Panicker MH, Barrett FS, Mathur BN, Seminowicz DA.
Resting state functional connectivity and cognitive task-related activation of
the human claustrum. Neuroimage. 2019 Apr 4;196:59-67. doi:
10.1016/j.neuroimage.2019.03.075. [Epub ahead of print] PubMed PMID: 30954711.
Wu, Junfang
 
Grants and Contracts:

NIH R01 NS110635--- Junfang Wu, BM, PhD, Associate Professor, together with Alan I Faden, MD, Professor, Department of Anesthesiology & Center for Shock, Trauma and Anesthesiology Research (STAR), received a five-year, $2,188,559 grant (MPI R01) from the National Institute of Neurological Disorders and Stroke (NINDS) for “Mechanism of Inflammatory-related Brain Dysfunction after Spinal Cord Injury”. (4/1/2019-3/31/2024)

NIH R01 NS110567--- Junfang Wu, BM, PhD, Associate Professor, together with Wei Chao, MD, Professor, and Lin Zou, PhD, Assistant Professor, Department of Anesthesiology & Center for Shock, Trauma and Anesthesiology Research (STAR), received a five-year, $2,549,260 grant (MPI R01) from the National Institute of Neurological Disorders and Stroke (NINDS) for “Targeting Brain Inflammation and Neurological Dysfunction in Sepsis”. (5/1/2019-2/29/2024)

Publication:
 
Sabirzhanov B, Li Y, Coll-Miro M, Matyas JJ, He J, Kumar A, Ward N, Yu J, Faden AI, Wu J. Inhibition of NOX2 signaling limits pain-related behavior and improves motor function in male mice after spinal cord injury: participation of IL-10/miR-155 pathways.
Brain, Behavior, and Immunity. 2019, [Epub ahead of print]. PMID: 30807841.

Presentation:

Junfang Wu presented “Risk of Dementia/Depression and Associated Inflammatory Mechanisms in Spinal Cord Injury” at The University of Texas Medical Branch at Galveston on May 29, 2019
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.