Amanda H. Klein PhD
Amanda H. Klein
PhD
Associate Professor
Department of Pharmacology and Toxicology
Jacobs School of Medicine & Biomedical Sciences
Specialty/Research Focus
Behavioral Neuroscience; Electrophysiology; Metabolism; Neurobiology; Neuropharmacology; Pain; Pharmacotherapy
Professional Summary:
My research lab focuses on the mechanisms of chronic pain and opioid signaling using in vitro and in vivo methods. My previous research training is comprehensive, covering fields of rodent behavior, metabolomics, spinal cord electrophysiology, cation imaging, histology, immunofluorescence, live-cell imaging, rodent and non-human primate nerve fiber recordings, compound action potential electrophysiology, and human psychophysics.
My research program targets several related topics related to changes in cell excitability and intracellular signaling during chronic pain and chronic drug exposure. Several lines of evidence suggest that common changes occur in the peripheral and central nervous system during these events. One key focus of my research program lies in answering questions regarding the development of opioid tolerance and opioid induced hypersensitivity. We are currently investigating how downstream effectors of opioid signaling, namely inwardly-rectifying potassium channels, contribute to analgesia and how loss of expression or function can change the maintenance and progression of enhanced sensitivity in the nervous system. The progression and persistence of chronic pain is a huge social and economic burden within the United States, and better understanding of the pathology of chronic pain, and ways to manage pain are desperately needed.
Alongside my bench work, a major priority of my research program is the development of novel therapeutics to treat pain and opioid induced tolerance and withdrawal.
Education and Training:
- Fellowship, Postdoctoral, Johns Hopkins University (2015)
- PhD, Molecular Cellular and Integrative Physiology, University of California Davis (2012)
- MS, Cellular Biology, University of Minnesota (2007)
- BS, Cellular Biology, University of Minnesota (2005)
Employment:
- Associate Professor, Pharmacology and Toxicology, University at Buffalo (2023-present)
- Associate Professor, Pharmacy Practice and Pharmaceutical Sciences, University of Minnesota (2023)
- Assistant Professor, Pharmacy Practice and Pharmaceutical Sciences, University of Minnesota (2015–2023)
Awards and Honors:
- Early Career Investigator Showcase Award (2025)
- Viewpoint Award (2024)
- McNair Scholar Mentor Award (2019)
- Loren D. Carlson Prize in Physiology (2013)
- Irving I. Hertzendorf Memorial Award in Physiology (2011)
Journal Articles:
- Martin MK, Rodriguez R, Guerrero G, Sheehan GD, Powell R, Klein AH, Bhattacharjee A. (2024) Pharmacologically enabling the degradation of NaV1.8 channels to reduce neuropathic pain. Pain (Nov).
- Fisher C, Johnson K, Moore M, Sadrati A, Janecek JL, Graham ML, Klein AH. (2024) Loss of ATP-Sensitive Potassium Channel Expression and Function in the Nervous System Decreases Opioid Sensitivity in a High-Fat Diet-Fed Mouse Model of Diet-Induced Obesity. Diabetes (Aug), 73(8): 1244-1254. doi:10.2337/db23-1030
- Doucette A, Johnson K, Hulke S, Mujteba S, Miller E, Meyer B, Dosa PI, Klein AH. (2023) KATP Channel Prodrugs Reduce Inflammatory and Neuropathic Hypersensitivity, Morphine-Induced Hypersensitivity, and Precipitated Withdrawal in Mice. The Journal of pharmacology and experimental therapeutics (Oct), 387(1): 18-26. doi:10.1124/jpet.122.001522
- Fisher C, Johnson K, Moore M, Sadrati A, Janecek JL, Graham ML, Klein AH. (2023) Loss of ATP-sensitive channel expression and function decreases opioid sensitivity in a mouse model of type 2 diabetes. bioRxiv : the preprint server for biology (Sep). doi:10.1101/2023.09.06.556526
- Johnson K, Doucette A, Edwards A, Verdi A, McFarland R, Hulke S, Fowler A, Watts VJ, Klein AH. (2022) Reduced activity of adenylyl cyclase 1 attenuates morphine induced hyperalgesia and inflammatory pain in mice. Frontiers in pharmacology (Jan), 13: 937741. doi:10.3389/fphar.2022.937741
- Sakamaki G, Johnson K, Mensinger M, Hmu E, Klein AH. (2021) Loss of SUR1 subtype KATP channels alters antinociception and locomotor activity after opioid administration. Behavioural brain research (Sep), 414: 113467.
- Klein A, Solinski HJ, Malewicz NM, Ieong HF, Sypek EI, Shimada SG, Hartke TV, Wooten M, Wu G, Dong X, Hoon MA, LaMotte RH, Ringkamp M. (2021) Pruriception and neuronal coding in nociceptor subtypes in human and nonhuman primates. eLife (Apr), 10. doi:10.7554/eLife.64506
- Okerman T, Jurgenson T, Moore M, Klein AH. (2021) Inhibition of the phosphoinositide 3-kinase-AKT-cyclic GMP-c-Jun N-terminal kinase signaling pathway attenuates the development of morphine tolerance in a mouse model of neuropathic pain. Molecular pain (Jan), 17: 17448069211003375. doi:10.1177/17448069211003375
- Luu W, Bjork J, Salo E, Entenmann N, Jurgenson T, Fisher C, Klein AH. (2019) Modulation of SUR1 KATP Channel Subunit Activity in the Peripheral Nervous System Reduces Mechanical Hyperalgesia after Nerve Injury in Mice. International journal of molecular sciences (May), 20(9). doi:10.3390/ijms20092251
- Simons CT, Klein AH, Carstens E. (2019) Chemogenic Subqualities of Mouthfeel. Chemical senses (May), 44(5): 281-288. doi:10.1093/chemse/bjz016
- Fisher C, Johnson K, Okerman T, Jurgenson T, Nickell A, Salo E, Moore M, Doucette A, Bjork J, Klein AH. (2019) Morphine Efficacy, Tolerance, and Hypersensitivity Are Altered After Modulation of SUR1 Subtype KATP Channel Activity in Mice. Frontiers in neuroscience (Jan), 13: 1122. doi:10.3389/fnins.2019.01122
- Klein AH. (2019) The orotrigeminal system. Handbook of clinical neurology (Jan), 164: 205-216.
- Klein AH, Mohammad HK, Ali R, Peper B, Wilson SP, Raja SN, Ringkamp M, Sweitzer S. (2018) Overexpression of µ-Opioid Receptors in Peripheral Afferents, but Not in Combination with Enkephalin, Decreases Neuropathic Pain Behavior and Enhances Opioid Analgesia in Mouse. Anesthesiology (May), 128(5): 967-983. doi:10.1097/ALN.0000000000002063
- Klein AH, Vyshnevska A, Hartke TV, De Col R, Mankowski JL, Turnquist B, Bosmans F, Reeh PW, Schmelz M, Carr RW, Ringkamp M. (2017) Sodium Channel Nav1.8 Underlies TTX-Resistant Axonal Action Potential Conduction in Somatosensory C-Fibers of Distal Cutaneous Nerves. The Journal of neuroscience : the official journal of the Society for Neuroscience (May), 37(20): 5204-5214. doi:10.1523/JNEUROSCI.3799-16.2017
- Klein AH, Trannyguen M, Joe CL, Iodi CM, Carstens E. (2015) Thermosensitive transient receptor potential (TRP) channel agonists and their role in mechanical, thermal and nociceptive sensations as assessed using animal models. Chemosensory perception (Aug), 8(2): 96-108. doi:10.1007/s12078-015-9176-9
- Wooten M, Weng HJ, Hartke TV, Borzan J, Klein AH, Turnquist B, Dong X, Meyer RA, Ringkamp M. (2014) Three functionally distinct classes of C-fibre nociceptors in primates. Nature communications (Jun), 5: 4122. doi:10.1038/ncomms5122
- Klein AH, Joe CL, Davoodi A, Takechi K, Carstens MI, Carstens E. (2014) Eugenol and carvacrol excite first- and second-order trigeminal neurons and enhance their heat-evoked responses. Neuroscience (Jun), 271: 45-55. doi:10.1016/j.neuroscience.2014.04.019
- Klein AH, Carstens MI, Carstens E. (2013) Eugenol and carvacrol induce temporally desensitizing patterns of oral irritation and enhance innocuous warmth and noxious heat sensation on the tongue. Pain (Oct), 154(10): 2078-2087. doi:10.1016/j.pain.2013.06.025
- Boucher Y, Felizardo R, Klein AH, Carstens MI, Carstens E. (2013) Gustatory modulation of the responses of trigeminal subnucleus caudalis neurons to noxious stimulation of the tongue in rats. The European journal of neuroscience (Sep), 38(6): 2812-22. doi:10.1111/ejn.12282
- Takechi K, Carstens MI, Klein AH, Carstens E. (2013) The antinociceptive and antihyperalgesic effects of topical propofol on dorsal horn neurons in the rat. Anesthesia and analgesia (Apr), 116(4): 932-8. doi:10.1213/ANE.0b013e31827f560d
- Klein AH, Sawyer CM, Takechi K, Davoodi A, Ivanov MA, Carstens MI, Carstens E. (2012) Topical hindpaw application of L-menthol decreases responsiveness to heat with biphasic effects on cold sensitivity of rat lumbar dorsal horn neurons. Neuroscience (Sep), 219: 234-42. doi:10.1016/j.neuroscience.2012.05.061
- Klein AH, Iodi Carstens M, McCluskey TS, Blancher G, Simons CT, Slack JP, Furrer S, Carstens E. (2011) Novel menthol-derived cooling compounds activate primary and second-order trigeminal sensory neurons and modulate lingual thermosensitivity. Chemical senses (Sep), 36(7): 649-58. doi:10.1093/chemse/bjr029
- Klein A, Carstens MI, Carstens E. (2011) Facial injections of pruritogens or algogens elicit distinct behavior responses in rats and excite overlapping populations of primary sensory and trigeminal subnucleus caudalis neurons. Journal of neurophysiology (Sep), 106(3): 1078-88. doi:10.1152/jn.00302.2011
- Klein AH, Sawyer CM, Zanotto KL, Ivanov MA, Cheung S, Carstens MI, Furrer S, Simons CT, Slack JP, Carstens E. (2011) A tingling sanshool derivative excites primary sensory neurons and elicits nocifensive behavior in rats. Journal of neurophysiology (Apr), 105(4): 1701-10. doi:10.1152/jn.00922.2010
- Klein AH, Carstens MI, Zanotto KL, Sawyer CM, Ivanov M, Cheung S, Carstens E. (2011) Self- and cross-desensitization of oral irritation by menthol and cinnamaldehyde (CA) via peripheral interactions at trigeminal sensory neurons. Chemical senses (Jan), 36(2): 199-208. doi:10.1093/chemse/bjq115
- Klein AH, Wendroth SM, Drewes LR, Andrews MT. (2010) Small-volume d-ß-hydroxybutyrate solution infusion increases survivability of lethal hemorrhagic shock in rats. Shock (Augusta, Ga.) (Dec), 34(6): 565-72.
- Klein AH, Sawyer CM, Carstens MI, Tsagareli MG, Tsiklauri N, Carstens E. (2010) Topical application of L-menthol induces heat analgesia, mechanical allodynia, and a biphasic effect on cold sensitivity in rats. Behavioural brain research (Oct), 212(2): 179-86. doi:10.1016/j.bbr.2010.04.015
- Tsagareli MG, Tsiklauri N, Zanotto KL, Carstens MI, Klein AH, Sawyer CM, Gurtskaia G, Abzianidze E, Carstens E. (2010) Behavioral evidence of thermal hyperalgesia and mechanical allodynia induced by intradermal cinnamaldehyde in rats. Neuroscience letters (Apr), 473(3): 233-6. doi:10.1016/j.neulet.2010.02.056
- Amanda H. Klein, Sabbir Alam, Kayla Johnson, Christian Kriner, Brie Beck, Bethany Nelson, Cassidy Hill, Belle Meyer, Jonas Mellang, Val J. Watts. (1900) Inhibition of adenylyl cyclase 1 (AC1) and exchange protein directly activated by cAMP (EPAC) restores ATP-sensitive potassium (KATP) channel activity after chronic opioid exposure. (Jan) doi:10.1101/2025.02.03.636278
Professional Memberships:
- American Society for Pharmacology and Experimental Therapeutics (2022–present)
- International Association for the Study of Pain (2010–present)
- Society for Neuroscience (2009–present)
Presentations:
- "Novel potassium channel modulators with the potential to reduce opioid withdrawal" SUD Final Demo Day. The Kerry Murphy Healey Center for Health Innovation and Entrepreneurship. Babson College (2024)
- "1. Phosphate ester prodrugs targeting KATP Channels Reduce Mechanical Hypersensitivity in Chronic Pain Models, and Attenuate Morphine Tolerance and Precipitated Withdrawal in Mice" The 18th Annual Pain Therapeutics Summit (2024)
- "2. Alam SM, Davidson EK, Johnson K, Fulton C, Klein AH, Watts V. Dynamic fluorescent cyclic AMP biosensors (cAADis) to study recombinant and endogenous adenylyl cyclase 1 (AC1) signaling in HEK3/6KO and SH-SY5Y cellular models." American Society for Pharmacology and Experimental Therapeutics (2024)
- "Novel pain relief to reduce opioid withdrawal" Babson College: Substance Abuse Disorder - Sprint. National Institutes on Drug Abuse and The Kerry Murphy Healey Center for Health Innovation and Entrepreneurship (2023)
Service Activities:
- NIH ZRG1 ICN-W (02) Special Emphasis Panel. Member Conflict: Alcohol and Motivated Behavior; NIH Grant Reviewer (2025)
- Interview incoming PhD Candidates for PPBS program; PPBS Interview Assignments (2025)
- This Committee is charged with providing scientific guidance on how best to advance pain research through the HEAL Initiative by proposing and prioritizing future-looking strategic research priorities that will advance the HEAL Initiative pain research mission for the next phase (~5 years). Virtual workshops to feature expert presentations and discussion in an open forum that will advance the understanding and knowledge within each focus area and will help each subcommittee develop research priorities. 3 hours x 3 subcomittees.; Developing HEAL Pain Strategic Research Priorities (2024)
- NIH 2025/01 ZGM1 RCB-T (SU) Support for Research Excellence (SuRE) R16 program; NIH Grant Reviewer (2024)
- Graduate Student Ambassador leadership team; Faculty Mentor - Career Day (2024–present)
- Jacobs School of Medicine and Biomedical Sciences, Neuroscience Day; Poster Session Facilitator (2024)
- UB Neuroscience Program; Pilot funding grant reviewer (2024)
- Tenure Candidate Review, Virginia Polytechnic University; Tenure Candidate Review (2024)
- Facilitate MS thesis defense due to loss of GEC member.; MS Thesis - replacement for GEC member (2024)
- NIH NPI 2024/10 Neurobiology of Pain and Itch (ad-hoc); NIH Grant Reviewer (2024)
- Backup for MS Research thesis defense - original committee member was missing. May 9th 2024; MS Thesis Defense (2024)
- Provide input for T32 Program. he Johns Hopkins School of Medicine offers a postdoctoral training program for both basic science and clinical researchers interested developing an academic career in pain research. Candidates must obtain their doctoral degree (MD, PHD, PSYD, DDS, etc.) prior to starting the fellowship. The training program is intended to develop postdoctoral trainees’ skills to become independent investigators in the interdisciplinary field of biobehavioral pain research. Candidates with some background in neuroscience or pain with evidence of commitment to a research career are preferred. The training program (1-2 years) incorporates coursework, mentored research experiences, an individual integrated research project, seminars, and exposure to professional development skills, including grant proposal and manuscript writing. In rare cases a third year may be possible. The overarching goal of the postdoctoral program is to prepare the next generation of innovative research leaders to work cooperatively within an interdisciplinary team to address the complex problem of pain. This program is supported by an NIH NINDS T32 training grant.; Johns Hopkins University T32 Pain Research Advisory Committee (2024–present)
- W.M. Keck Foundation. Science & Engineering and Medical Research Grant; Private foundation grant reviewer (2024)
- PMY Graduate Group - Member; Graduate Education Committee Meeting (2024–present)
- NIH ZNS1 SRB-S (20) HEAL R61. HEAL Initiative: Non-addictive Analgesic Therapeutics Development [Small Molecules and Biologics] to Treat Pain; NIH Grant Reviewer (2024)
- PMY Graduate Program - submit feedback to 2nd year Master's students; Review Master's Research Presentations (2024)
- Scientific Reports, Behavioral Pharmacology, The Journal of Physiology, Journal of Neuroinflammation, European Journal of Pharmacology, Neuropharmacology, Journal of Pain Research, Journal of Pharmacology and Experimental Therapeutics, Neuroscience; Manuscript Reviews (2024)
- Medical Student Annual Research Forum January 24 2024; Faculty facilitator and Poster Session Judge (2024)
- Discuss membership and participation across 6,000 members around the world; Membership and Chapters Committee - International Association for the Study of Pain (2024–present)