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Armen N. Akopian, Ph.D.
Dental School
Endodontics
210-567-6668
akopian@uthscsa.edu
Chronic pain is one of the most prevalent human health problems, affecting over 25% of the world’s population. Although overall improvement in the clinical management of chronic pain is documented, an epidemic increase in opioid analgesic use and related overdose deaths over the last few decades is reported. These issues mandate mechanistic studies, which have been actively promoted, in an attempt to understand underlying mechanisms controlling the process of development of chronic pain.
The chronic pain mechanisms control maintenance and resolution of persistent phase of pain conditions. There is consensus that these mechanisms could be result of neuro-immune and neuro-endocrine interactions. Besides, pain chronicity is a sex- and age-dependent phenomenon. Many inflammatory and idiopathic chronic pain conditions, such as migraine, fibromyalgia, TMD, rheumatoid arthritis, have 2-6-fold greater prevalence and/or symptom severity in women as compared to men. There have been little-to-no understanding mechanisms controlling development of chronic pain in the elderly. Thus, standard analgesics act differently in aged individuals. Moreover, interestingly, pain chronicity is relatively infrequent in the elderly compare to young and adult individuals.
Main research interests of Dr. Armen Akopian's lab are to understand (1) sex-dependent mechanism controlling pain chronicity; (2) age-dependent mechanisms controlling pain chronicity; (3) understanding mechanisms underlying sex- and age-dependent efficacy and tolerance of standard analgesics; and (4) general mechanism controlling maintenance and resolution of pain at different conditions. Accordingly, our current projects are investigating:
(1) Roles of pituitary hormones in control of sex-specific mechanisms of pain chronicity
(2) Neuro-endocrine meningeal mechanisms underlying female-selectivity of migraine
(3) Neuro-immune mechanisms of orofacial pain chronicity
(4) Interaction of non-neuronal cells in sensory neurons in regulation of painful neuropathies
The lab uses a multidisciplinary research approach that includes electrophysiology, behavioral physiology, anatomy, pharmacology, cell imaging, RNA-sequencing, transgenic mouse technology, biochemistry and cell biology.
Diseases Associated: Postoperative pain, Inflammatory pain, TMD/TMJ, Migraine, Chemotherapy-induced painful neuropathis
Specific Field of Study: General, sex and age-dependent mechanisms of pain chronicity
Techniques Used: Behavioral preclinical models, imaging in vitro and in vivo, electrophysiology, sequencing, transgenic mice, general biochemistry and cell biology approaches.
Neuroscience
We investigate conceptually novel mechanisms linking prolactin to female-selective control of certain types of migraine. We investigate a conceptually novel mechanism for the transition from acute to chronic pain in females, which is based on sex-specific local translation in nociceptive synapses and its regulation by gonadal hormones and prolactin.
Diseases Associated: Postoperative pain Chemotherapy-induced pain TMD/TMJ Migraine
Specific Field of Study: General, sex and age-dependent mechanisms of pain chronicity
Techniques Used: Imaging in vitro and in vivo Electro-physiology Sequencing Transgenic mice Behavioral physiology
Education
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| Year | Degree | Discipline | Institution |
| 2001 | Postdoctoral Fellowship | Molecular Neuroscience, Research Fellow | University College of London London, United Kingdom |
| 1997 | Postdoctoral Fellowship | Molecular Neuroscience, Postdoctoral Fellowship | University College of London London, United Kingdom |
| 1994 | PhD | Biochemistry, Molecular Biology & Science | Engelhardt Institute of Molecular Biology, Branch of Biological Sciences Moscow, USSR |
| 1994 | Postdoctoral Fellowship | Medical Research, Postdoc Fellowship | Sandoz Institute of Medical Research London, United Kingdom |
| 1987 | MS | Biology | Moscow State University |
| 1985 | BS | Physics | Moscow State University |
Appointments
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| 1/2013 - Present | Associate Professor with Tenure | University of Texas Health Science Center at San Antonio |
| 6/2011 - Present | Credentialed Mentoring Faculty Member | Graduate School of Biomedical Sciences, UTHSCSA, Pharmacology, San Antonio, TX |
Expertise
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Biochemistry - This includes protein isolation and protein fraction enrichment, Western blot electrophoresis and immunoprecipitation. |
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Electrophysiology - This includes all aspects of patch clamp electrophysiology and extracellular recording. |
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Fluorescent imaging - This includes live imaging and calcium-imaging. |
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Future scientific Plans - Future scientific plans for at least the next 5-8 years will be to work on these three aforementioned projects in which overall goals are to substantially contribute to improving treatment of chronic pain with no opioids. I aim for not only understanding the mechanisms controlling the development of chronic pain, but to also discover promising therapeutic targets. I planned to obtain external funding support for these projects, and develop novel and contemporary approaches to facilitate solving questions raised by these projects. In this regard, our collaborative team is working hard to set up two contemporary approaches: single-cell sequencing and in vivo live imaging with two-photon microscopy. Thus, we (I am PI) submitted an S10 equipment grant to the NIH in June 2018 to support purchasing a 2-photon microscope system. Importantly, I conduct my research program with my graduate students and post-doctoral fellows. Thus, my research and teaching efforts are combined and execute simultaneously to meaningfully address the critical problem of chronic pain. |
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Molecular and cellular biology - This includes Isolation and synthesis of nucleic acids: DNA and RNA, construction of vectors and libraries, screening of genomic and cDNA libraries, in situ hybridization (non-radioactive and radioactive), and transfection and propagations of cell lines (primary and secondary). |
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Next Generation Sequencing - This includes RNA-seq from tissue samples and single-cell sequencing. |
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Pain modulation in pathological conditions - (inflammatory and neuropathic pain) |
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Research Program - My main area of research interest is to understand how chronic pain develops, especially mechanisms controlling the transition to and resolution from chronic pain conditions. Chronic pain mismanagement has led to opioid overuse, overdose related deaths and cardiovascular, renal and neurological complications at epidemic proportions. In this regard, several Institutes and Centers across the NIH support the ?Acute to Chronic Pain Signatures program?, including UM1, U24 and U54 funding opportunities. To address mechanisms of chronic pain, I started (from 2016-2018) three independent projects related to sex-dependent mechanisms of pain chronicity, age-dependent mechanisms of pain chronicity and peripheral mechanisms of pain chronicity. Projects associated with sex-dependent mechanisms of pain chronicity were recently (2018) awarded with two R01 grants (R01 NS102161 and R01 NS104200). Of particular relevance, these two new R01 grants were scored at the 1% and 2% levels (i.e., they better scores than 99% and 98% of all grants submitted to the NIH, respectively). This provides an independent assessment of the scientific impact of my research program. The other two project lines will form the basis of two additional R01 grants to be submitted in FY19. |
Publications
Journal Article |
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Ray PR, Sankaranarayanan I, Mejia GL, Wangzhou A, Shiers S, Uttarkar R, Megat S, Barragan-Iglesias P, Dussor G, Akopian AN and Price TJ. Sex Differences in Nociceptor Translatomes Contribute to Divergent Prostaglandin Signaling in Male and Female Mice. Biol Psychiatry 2020 Oct 5; S0006-3223 (20) 31952-1 |
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Mecklenburg J, You, Y., Wangzhou A., Garcia D., Lai Z., Tumanov A.V., Dussor G, Price TJ and Akopian AN Transcriptomic sex differences in sensory neuronal populations of mice Scientific Reports volume 10, Issue 1, 1 December 2020, Article number 15278 |
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Paige C, Barba-Escobedo PA, Mecklenburg J, Patil M, Goffin V, Grattan D, Dussor G, Akopian AN* and Price TJ* Neuroendocrine mechanisms governing sex-differences in chronic pain involve prolactin receptor sensory neuron signaling J. Neurosci Volume 40, Issue 37, 9 September 2020, Pages 7080-7090 |
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Avona A., Mason BN, Lackovic J, Wajahat N, Motina M, Quigley L, Burgos-Vega V, Loomis CM, Garcia-Martinez LF, Akopian AN, Price TJ, and Dussor G. Repetitive stress in mice causes migraine-like behaviors and CGRP-dependent hyperalgesic priming to a migraine trigger. Pain 6/10/2020 |
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Hassler, S.N., Kume, M., Mwirigi, J.M., Ahmad, A., Shiers, S., Wangzhou, A., Ray, P.R., Belugin, S.N., Naik, D.K., Burton, M.D., Vagner, J., Boitano, S., Akopian, A.N., Dussor, G., and Price, T.J. The cellular basis of protease-activated receptor 2-evoked mechanical and affective pain. JCI Insight Volume 5, Issue 11, 4 June 2020 |
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Chen, Y., Moutal, A., Navratilova, E., Kopruszinski, C., Yue, X., Ikegami, M., Chow, M., Kanazawa, I., Bellampalli, S.S., Xie, J., Patwardhan, A., Rice, K., Fields, H., Akopian, A., Neugebauer, V., Dodick, D., Khanna, R., and Porreca, F. The prolactin receptor long isoform regulates nociceptor sensitization and opioid-induced hyperalgesia selectively in females. Science Translational Medicine Volume 12, Issue 529, 5 February 2020, Article number eaay7550 |
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Patil, M.J., Salas, M., Bialuhin, S., Boyd, J.T., Jeske, N.A., and Akopian, A.N. Sensitization of small-diameter sensory neurons is controlled by TRPV1 and TRPA1 association. FASEB Journal Volume 34, Issue 1, 1 January 2020, Pages 287-302 |
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Patil, M., Belugin, S., Mecklenburg, J., Wangzhou, A., Paige, C., Barba-Escobedo, P.A., Boyd, J.T., Goffin, V., Grattan, D., Boehm, U., Dussor, G., Price, T.J. and Akopian, A.N. Prolactin Regulates Pain Responses via a Female-Selective Nociceptor-Specific Mechanism. iScience Volume 20, 25 October 2019, Pages 449-465 |
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Avona, A., Burgos-Ega, C., Burton, M.D., Akopian, A.N., Price, T.J., and Dussor, G. Dural calcitonin gene-related peptide produces female-specific responses in rodent migraine models. J. Neurosci. Volume 39, Issue 22, 29 May 2019, Pages 4323-4331 |
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Ray, P.R., Khan, J., Wangzhou, A., Tavares-Ferreira, D., Akopian, A.N., Dussor, G, and Price, T.J. Transcriptome analysis of the human tibial nerve identifies sexually dimorphic expression of genes involved in pain, inflammation, and neuro-immunity. Frontiers in Molecular NeuroscienceVolume 12, 12 February 2019, Article number 37 |
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Patil, M., Hovhannisyan, A.H., Wangzhou, A., Mecklenburg, J., Koek, W., Goffin, V., Grattan, D., Boehm, U., Dussor, G., Price, T.J., and Akopian, A.N. Prolactin receptor expression in mouse dorsal root ganglia neuronal subtypes is sex-dependent. J. Neuroendo. Volume 31, Issue 8, 2019, Article number e12759 |
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Dussor, G., Boyd, J.T., and Akopian, A.N. Pituitary hormones and orofacial pain. Frontiers in Integrative Neuroscience Volume 12, 2 October 2018, Article number 42 |
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Akopian AN, Hovhannisyn, AH, Patil, Mayur M. Characteristics of sensory neuronal groups in CGRP-1 cre-ER reporter mice: Comparison to Nav1.8-cre, TRPV1-cre and TRPV1-GFP mouse lines Public Library of Science 2018 Jan;13(6). |
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Mecklenburg J, Patil M, Koek W, Akopian AN. Effects of local and spinal administrations of mu-opioids on postoperative pain in aged vs adult mice Pain Reports 2017 Jan;. |
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Akopian AN, Brackley, AD, Gomez, R, Guerrero, KA, Glucksman, MJ, Du, J, Carlton, SM, Jeske NA. A-Kinase Anchoring Protein 79/150 Scaffolds Transient Receptor Potential A 1 Phosphorylation and Sensitization by Metabotropic Glutamate Receptor Activation Scientific Reports 2017 Jan;7(1). |
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Akopian AN, Fanick ER, Brook EG. TRP channels and traffic-related environmental pollution-induced pulmonary disease Semin Immunopathol 2016 May;38(3):331-338. |
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Patil M,Henry M, Goffin V, Akopian AN. (300) Prolactin regulates sensory neurons in a female-specific manner at their peripheral and central terminals and not at their cell bodies The Journal of Pain 2016 Jan;17(4). |
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Grattan DR, Akopian AN. Oscillating from Neurosecretion to Multitasking Dopamine Neurons Cell Report 2016 Jan;15(4):681-682. |
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Akopian AN et. al. The TRPA1 ion channel is expressed in CD4 T cells and restrains T-cell-mediated colitis through inhibition of TRPV1 Gut 2016 Jan;. |
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Akopian AN. Role of TRP ion channels in physiology and pathology Semin Immunopathol 2016 Jan;38(3):275-276. |
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Green D, Patil M, Akopian AN. Influence of Hypophysectomy, Ovariectomy and Gonadectomy on Postoperative Hypersensitivity in Rats Global Anesthesia and Perioperative Medicine 2016 Jan;2(2):171-175. |
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Green D, Ruparel S, Gao X, Ruparel N, Patil M, Akopian A, Hargreaves K. Central activation of TRPV1 and TRPA1 by novel endogenous agonists contributes to mechanical allodynia and thermal hyperalgesia after burn injury Molecular Pain 2016 Jan;. |
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Brackley AD, Gomez R, Akopian AN, Henry MA, Jeske NA. GRK2 Constitutively Governs Peripheral Delta Opioid Receptor Activity Cell Report 2016 Jan;16(10):2686-2698. |
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Weng H-J, Patel KN, Jeske NA, Bierbower SM, Zou W, Tiari V, Zheng Q, Tang Z, Mo GCH, Wang Y, Geng Y, Zhang J, Guan Y, Akopian AN, Dong X. Tmem100 is a regulator of TRPA1-TRPV1 complex and contributes to persistent pain Neuron 2015 Jan;85:1-14. |
Teaching
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| Date | Description | Institution | # Students |
| 1/2017 - Present | Post-Doctoral Student Supervision | University of Texas Health Science Center at San Antonio | |
| 1/2016 - Present | Pre-Doctoral Student Supervision | University of Texas Health Science Center at San Antonio | |
| 1/2000 - Present | Individual Instruction | UT Health San Antonio | |
Grants
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| Funding Agency | NIH/NINDS (R01 NS112263-01A1) |
| Title | Lymphotoxin-beta receptor peripheral signaling regulates the transition to inflammation and neuropathy-induced chronic pain |
| Period | 2020-2025 |
| Role | Principal Investigator |
| Grant Detail |
The proposed research major goal is to understand underlying mechanisms controlling transition from acute to chronic pain state for inflammatory chemotherapy-induced pain conditions. |
| Funding Agency | NIH/NIDCR (R01 DE029187) |
| Title |
LIGHT and Lymphotoxin targeting for the treatment of chronic orofacial pain conditions |
| Period | 2019 - 8/2024 |
| Role |
(Multi-PI: Akopian, Ruparel and Tumanov) |
| Grant Detail |
The proposed research major goal is to advance our understanding of mechanisms regulating the development and maintenance of orofacial pain; and offers targets and an immunotherapeutic approach for preventing and blocking chronic pain during TMJD and oral cancer. |
| Funding Agency | NIH/NNDS |
| Title | Meningeal prolactin signaling and female-selective migraine mechanisms |
| Status | Active |
| Period | 8/2018 - 8/2023 |
| Role | Principal Investigator |
| Grant Detail |
The major goals of this project are to investigate the role of meningeal prolactin system in female-selective mechanisms of migraine triggered by vasodilatory hormone CGRP and stress. |
| Funding Agency | NIH |
| Title | Sex-Specific regulation of local translation and chronic pain mechanisms in females |
| Status | Active |
| Period | 7/2018 - 6/2023 |
| Role |
Principal Investigator |
| Grant Detail |
The major goals of this project are to investigate sexual dimorphism of the transition from acute to chronic pain and the control of this process by gonadal hormones that regulate local translation in nociceptor terminals. |
| Funding Agency | NIH |
| Title | Prolactin regulation of postoperative pain in males and females |
| Status | Active |
| Period | 9/2015 - 8/2019 |
| Role | Principal Investigator |
| Grant Detail | The major goals of this project are to identify and characterize female-specific mechanisms in regulation of postoperative pain |