Andrea Gail Nackley | Scholars@Duke

Andrea Gail Nackley
Associate Professor in Anesthesiology

Pain is a multidimensional sensory and emotional experience that is important for our survival, but once pain becomes chronic it is no longer beneficial and, instead, becomes a disorder in and of itself. Chronic pain remains one of our nation’s most significant healthcare problems due to a limited understanding of the underlying genetic and environmental factors. There are three main objectives of our lab’s research in this area:

To determine the factors that put some people, but not others, at risk for maladaptive chronic pain conditions. To achieve this objective, we study genetic, biological, and environmental factors associated with the initial onset of pain as well as its severity and duration. In addition, we are beginning to study factors associated with patient-centered outcomes, which may have the power to predict optimal management strategies for different individuals.
To elucidate the mechanism(s) whereby genetic, biological, and environmental factors drive chronic pain. To achieve this objective, we integrate molecular genetics, animal models, and clinical epidemiologic measures in order to reveal pathogenic processes that are unique to as well as common across a particular condition or individual(s). This line of inquiry will provide novel targets for the development of individualized therapeutics for the management of chronic pain.
To improve pharmacologic management of pain. To achieve this objective, we conduct pre-clinical studies to test the efficacy of new compounds and to optimize the efficacy of existing compounds in patient-relevant animal models.

Current Appointments & Affiliations

Associate Professor in Anesthesiology, Anesthesiology, Clinical Science Departments 2019
Associate Professor in Pharmacology and Cancer Biology, Pharmacology & Cancer Biology, Basic Science Departments 2017

Contact Information

3 Genome Court, #6120, Durham, NC 27710
Box 3094, Mail Sort #50, Durham, NC 27710
andrea.nackley@duke.edu (919) 613-5911
Nackley Lab URL

Background
Education, Training, & Certifications
- Ph.D., University of Georgia 2003
Previous Appointments & Affiliations
- Associate Professor in Anesthesiology, Anesthesiology, Clinical Science Departments 2016 - 2019
- Instructor Temporary in the Department of Anesthesiology, Anesthesiology, Clinical Science Departments 2015 - 2016
Expertise
Subject Headings
Research
Selected Grants
- Integrated Training in Anesthesiology Research awarded by National Institutes of Health 1996 - 2026
- Institutional Summer Undergraduate Research Fellowship (SURF) awarded by American Society for Pharmacology and Experimental Therapeutics 2018 - 2025
- A novel clinically- relevant mouse model of chronic overlapping pain conditions for screening analgesics awarded by National Institutes of Health 2022 - 2023
- Assay Development for characterization of Adrb3 antagonists as pain therapeutics awarded by Research Triangle Institute International 2021 - 2022
- Defining the role of peripheral Adrb3 in chronic pain and inflammation awarded by National Institutes of Health 2019 - 2022
- Defining the role of adipocyte-specific Adrb3 in chronic pain awarded by National Institutes of Health 2018 - 2019
- Proteins, MicroRNAs and Genes Associated with TMD and Overlapping Pain Conditions awarded by National Institutes of Health 2016 - 2018
Publications & Artistic Works
Selected Publications
- Academic Articles
  - Wang, Yaomin, Scott A. Scarneo, Shin Hyung Kim, Xin Zhang, Jiegen Chen, Kelly W. Yang, Philip Hughes, Timothy Haystead, and Andrea G. Nackley. “Expression of ectopic heat shock protein 90 in male and female primary afferent nociceptors regulates inflammatory pain.” Pain 163, no. 6 (June 1, 2022): 1091–1101. https://doi.org/10.1097/j.pain.0000000000002511.
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  - Parisien, Marc, Lucas V. Lima, Concetta Dagostino, Nehme El-Hachem, Gillian L. Drury, Audrey V. Grant, Jonathan Huising, et al. “Acute inflammatory response via neutrophil activation protects against the development of chronic pain.” Sci Transl Med 14, no. 644 (May 11, 2022): eabj9954. https://doi.org/10.1126/scitranslmed.abj9954.
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  - Luo, Xin, Ouyang Chen, Zilong Wang, Sangsu Bang, Jasmine Ji, Sang Hoon Lee, Yul Huh, et al. “IL-23/IL-17A/TRPV1 axis produces mechanical pain via macrophage-sensory neuron crosstalk in female mice.” Neuron 109, no. 17 (September 1, 2021): 2691-2706.e5. https://doi.org/10.1016/j.neuron.2021.06.015.
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  - Chen, Yong, Zi-Long Wang, Michele Yeo, Qiao-Juan Zhang, Ana E. López-Romero, Hui-Ping Ding, Xin Zhang, et al. “Epithelia-Sensory Neuron Cross Talk Underlies Cholestatic Itch Induced by Lysophosphatidylcholine.” Gastroenterology 161, no. 1 (July 2021): 301-317.e16. https://doi.org/10.1053/j.gastro.2021.03.049.
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  - Gaynor, Sheila M., Andrey Bortsov, Eric Bair, Roger B. Fillingim, Joel D. Greenspan, Richard Ohrbach, Luda Diatchenko, et al. “Phenotypic profile clustering pragmatically identifies diagnostically and mechanistically informative subgroups of chronic pain patients.” Pain 162, no. 5 (May 2021): 1528–38. https://doi.org/10.1097/j.pain.0000000000002153.
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  - Khoury, Samar, Qiao-Ping Wang, Marc Parisien, Pavel Gris, Andrey V. Bortsov, Sarah D. Linnstaedt, Samuel A. McLean, et al. “Multi-ethnic GWAS and meta-analysis of sleep quality identify MPP6 as a novel gene that functions in sleep center neurons.” Sleep 44, no. 3 (March 12, 2021). https://doi.org/10.1093/sleep/zsaa211.
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  - Ji, Jasmine, Qianru He, Xin Luo, Sangsu Bang, Yutaka Matsuoka, Aidan McGinnis, Andrea G. Nackley, and Ru-Rong Ji. “IL-23 Enhances C-Fiber-Mediated and Blue Light-Induced Spontaneous Pain in Female Mice.” Front Immunol 12 (2021): 787565. https://doi.org/10.3389/fimmu.2021.787565.
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  - Tilburg, Miranda A. L. van, Marc Parisien, Richard G. Boles, Gillian L. Drury, Julian Smith-Voudouris, Vivek Verma, Samar Khoury, et al. “A genetic polymorphism that is associated with mitochondrial energy metabolism increases risk of fibromyalgia.” Pain 161, no. 12 (December 2020): 2860–71. https://doi.org/10.1097/j.pain.0000000000001996.
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  - Zhang, Xin, Katie Kanter, Jiegen Chen, Seungtae Kim, Yaomin Wang, Clementine Adeyemi, Sandra C. O’Buckley, and Andrea G. Nackley. “Low catechol-O-methyltransferase and stress potentiate functional pain and depressive behavior, especially in female mice.” Pain 161, no. 2 (February 2020): 446–58. https://doi.org/10.1097/j.pain.0000000000001734.
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  - Smith, Shad B., Marc Parisien, Eric Bair, Inna Belfer, Anne-Julie Chabot-Doré, Pavel Gris, Samar Khoury, et al. “Genome-wide association reveals contribution of MRAS to painful temporomandibular disorder in males.” Pain 160, no. 3 (March 2019): 579–91. https://doi.org/10.1097/j.pain.0000000000001438.
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  - Kim, Seungtae, Xin Zhang, Sandra C. O’Buckley, Mary Cooter, Jongbae J. Park, and Andrea G. Nackley. “Acupuncture Resolves Persistent Pain and Neuroinflammation in a Mouse Model of Chronic Overlapping Pain Conditions.” J Pain 19, no. 12 (December 2018): 1384.e1-1384.e14. https://doi.org/10.1016/j.jpain.2018.05.013.
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  - Zhang, Xin, Jane E. Hartung, Andrey V. Bortsov, Seungtae Kim, Sandra C. O’Buckley, Julia Kozlowski, and Andrea G. Nackley. “Sustained stimulation of β2- and β3-adrenergic receptors leads to persistent functional pain and neuroinflammation.” Brain Behav Immun 73 (October 2018): 520–32. https://doi.org/10.1016/j.bbi.2018.06.017.
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  - Shepherd, Sarah D., Sandra C. O’Buckley, James M. Harrington, Laura G. Haines, Ginger D. Rothrock, Leah M. Johnson, and Andrea G. Nackley. “A moldable sustained release bupivacaine formulation for tailored treatment of postoperative dental pain.” Sci Rep 8, no. 1 (August 15, 2018): 12172. https://doi.org/10.1038/s41598-018-29696-w.
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  - Han, Qingjian, Di Liu, Marino Convertino, Zilong Wang, Changyu Jiang, Yong Ho Kim, Xin Luo, et al. “miRNA-711 Binds and Activates TRPA1 Extracellularly to Evoke Acute and Chronic Pruritus.” Neuron 99, no. 3 (August 8, 2018): 449-463.e6. https://doi.org/10.1016/j.neuron.2018.06.039.
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  - Ji, Ru-Rong, Andrea Nackley, Yul Huh, Niccolò Terrando, and William Maixner. “Neuroinflammation and Central Sensitization in Chronic and Widespread Pain.” Anesthesiology 129, no. 2 (August 2018): 343–66. https://doi.org/10.1097/ALN.0000000000002130.
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  - Martin, Loren J., Shad B. Smith, Arkady Khoutorsky, Claire A. Magnussen, Alexander Samoshkin, Robert E. Sorge, Chulmin Cho, et al. “Epiregulin and EGFR interactions are involved in pain processing.” J Clin Invest 127, no. 9 (September 1, 2017): 3353–66. https://doi.org/10.1172/JCI87406.
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  - Geller, Elizabeth J., Emma Babb, Andrea G. Nackley, and Denniz Zolnoun. “Incidence and Risk Factors for Pelvic Pain After Mesh Implant Surgery for the Treatment of Pelvic Floor Disorders.” Journal of Minimally Invasive Gynecology 24, no. 1 (January 2017): 67–73. https://doi.org/10.1016/j.jmig.2016.10.001.
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  - Ciszek, Brittney P., Sandra C. O’Buckley, and Andrea G. Nackley. “Persistent Catechol-O-methyltransferase-dependent Pain Is Initiated by Peripheral β-Adrenergic Receptors.” Anesthesiology 124, no. 5 (May 2016): 1122–35. https://doi.org/10.1097/ALN.0000000000001070.
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  - Oladosu, Folabomi A., Brittney P. Ciszek, Sandra C. O’Buckley, and Andrea G. Nackley. “Novel intrathecal and subcutaneous catheter delivery systems in the mouse.” J Neurosci Methods 264 (May 1, 2016): 119–28. https://doi.org/10.1016/j.jneumeth.2016.03.006.
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  - Ciszek, Brittney P., Asma A. Khan, Hong Dang, Gary D. Slade, Shad Smith, Eric Bair, William Maixner, Denniz Zolnoun, and Andrea G. Nackley. “MicroRNA expression profiles differentiate chronic pain condition subtypes.” Transl Res 166, no. 6 (December 2015): 706-720.e11. https://doi.org/10.1016/j.trsl.2015.06.008.
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  - Hartung, Jane E., Olivia Eskew, Terrence Wong, Inna E. Tchivileva, Folabomi A. Oladosu, Sandra C. O’Buckley, and Andrea G. Nackley. “Nuclear factor-kappa B regulates pain and COMT expression in a rodent model of inflammation.” Brain Behav Immun 50 (November 2015): 196–202. https://doi.org/10.1016/j.bbi.2015.07.014.
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  - Applebaum, Elizabeth, Andrea G. Nackley, Eric Bair, William Maixner, and Asma A. Khan. “Genetic Variants in Cyclooxygenase-2 Contribute to Post-treatment Pain among Endodontic Patients.” J Endod 41, no. 8 (August 2015): 1214–18. https://doi.org/10.1016/j.joen.2015.04.021.
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  - Oladosu, Folabomi A., William Maixner, and Andrea G. Nackley. “Alternative Splicing of G Protein-Coupled Receptors: Relevance to Pain Management.” Mayo Clin Proc 90, no. 8 (August 2015): 1135–51. https://doi.org/10.1016/j.mayocp.2015.06.010.
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  - Kline, R. H., F. G. Exposto, S. C. O’Buckley, K. N. Westlund, and A. G. Nackley. “Catechol-O-methyltransferase inhibition alters pain and anxiety-related volitional behaviors through activation of β-adrenergic receptors in the rat.” Neuroscience 290 (April 2, 2015): 561–69. https://doi.org/10.1016/j.neuroscience.2015.01.064.
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  - Oladosu, Folabomi A., Matthew S. Conrad, Sandra C. O’Buckley, Naim U. Rashid, Gary D. Slade, and Andrea G. Nackley. “Mu Opioid Splice Variant MOR-1K Contributes to the Development of Opioid-Induced Hyperalgesia.” Plos One 10, no. 8 (2015): e0135711. https://doi.org/10.1371/journal.pone.0135711.
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  - Smith, Shad B., Ilkka Reenilä, Pekka T. Männistö, Gary D. Slade, William Maixner, Luda Diatchenko, and Andrea G. Nackley. “Epistasis between polymorphisms in COMT, ESR1, and GCH1 influences COMT enzyme activity and pain.” Pain 155, no. 11 (November 2014): 2390–99. https://doi.org/10.1016/j.pain.2014.09.009.
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  - Hartung, Jane E., Brittney P. Ciszek, and Andrea G. Nackley. “β2- and β3-adrenergic receptors drive COMT-dependent pain by increasing production of nitric oxide and cytokines.” Pain 155, no. 7 (July 2014): 1346–55. https://doi.org/10.1016/j.pain.2014.04.011.
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  - Chen, Hong, Andrea Nackley, Vanessa Miller, Luda Diatchenko, and William Maixner. “Multisystem dysregulation in painful temporomandibular disorders.” J Pain 14, no. 9 (September 2013): 983–96. https://doi.org/10.1016/j.jpain.2013.03.011.
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  - Sanders, Anne E., William Maixner, Andrea G. Nackley, Luda Diatchenko, Kunthel By, Vanessa E. Miller, and Gary D. Slade. “Excess risk of temporomandibular disorder associated with cigarette smoking in young adults.” J Pain 13, no. 1 (January 2012): 21–31. https://doi.org/10.1016/j.jpain.2011.08.003.
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  - Slade, Gary D., Mathew S. Conrad, Luda Diatchenko, Naim U. Rashid, Sheng Zhong, Shad Smith, Jesse Rhodes, et al. “Cytokine biomarkers and chronic pain: association of genes, transcription, and circulating proteins with temporomandibular disorders and widespread palpation tenderness.” Pain 152, no. 12 (December 2011): 2802–12. https://doi.org/10.1016/j.pain.2011.09.005.
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  - Segall, S. K., A. G. Nackley, L. Diatchenko, W. R. Lariviere, X. Lu, J. S. Marron, L. Grabowski-Boase, et al. “Comt1 genotype and expression predicts anxiety and nociceptive sensitivity in inbred strains of mice.” Genes Brain Behav 9, no. 8 (November 2010): 933–46. https://doi.org/10.1111/j.1601-183X.2010.00633.x.
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  - Cevidanes, L. H. S., A. -. K. Hajati, B. Paniagua, P. F. Lim, D. G. Walker, G. Palconet, A. G. Nackley, et al. “Quantification of condylar resorption in temporomandibular joint osteoarthritis.” Oral Surg Oral Med Oral Pathol Oral Radiol Endod 110, no. 1 (July 2010): 110–17. https://doi.org/10.1016/j.tripleo.2010.01.008.
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  - Gris, Pavel, Josee Gauthier, Philip Cheng, Dustin G. Gibson, Denis Gris, Oskar Laur, John Pierson, et al. “A novel alternatively spliced isoform of the mu-opioid receptor: functional antagonism.” Mol Pain 6 (June 2, 2010): 33. https://doi.org/10.1186/1744-8069-6-33.
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  - Nackley, Andrea G., and Luda Diatchenko. “Assessing potential functionality of catechol-O-methyltransferase (COMT) polymorphisms associated with pain sensitivity and temporomandibular joint disorders.” Methods Mol Biol 617 (2010): 375–93. https://doi.org/10.1007/978-1-60327-323-7_28.
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  - Tchivileva, Inna E., Kai Soo Tan, Maria Gambarian, Andrea G. Nackley, Alexander V. Medvedev, Sergei Romanov, Patrick M. Flood, William Maixner, Sergei S. Makarov, and Luda Diatchenko. “Signaling pathways mediating beta3-adrenergic receptor-induced production of interleukin-6 in adipocytes.” Mol Immunol 46, no. 11–12 (July 2009): 2256–66. https://doi.org/10.1016/j.molimm.2009.04.008.
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  - Tchivileva, Inna E., Andrea G. Nackley, Li Qian, Sean Wentworth, Matthew Conrad, and Luda B. Diatchenko. “Characterization of NF-kB-mediated inhibition of catechol-O-methyltransferase.” Mol Pain 5 (March 16, 2009): 13. https://doi.org/10.1186/1744-8069-5-13.
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  - Nackley, Andrea G., Svetlana A. Shabalina, Jason E. Lambert, Mathew S. Conrad, Dustin G. Gibson, Alexey N. Spiridonov, Sarah K. Satterfield, and Luda Diatchenko. “Low enzymatic activity haplotypes of the human catechol-O-methyltransferase gene: enrichment for marker SNPs.” Plos One 4, no. 4 (2009): e5237. https://doi.org/10.1371/journal.pone.0005237.
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  - Diatchenko, Luda, Andrea G. Nackley, Inna E. Tchivileva, Svetlana A. Shabalina, and William Maixner. “Genetic architecture of human pain perception.” Trends Genet 23, no. 12 (December 2007): 605–13. https://doi.org/10.1016/j.tig.2007.09.004.
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  - Diatchenko, Luda, Andrea G. Nackley, Gary D. Slade, Inna Belfer, Mitchell B. Max, David Goldman, and William Maixner. “Responses to Drs. Kim and Dionne regarding comments on Diatchenko, et al. Catechol-O-methyltransferase gene polymorphisms are associated with multiple pain-evoking stimuli. Pain 2006; 125: 216-24.” Pain 129, no. 3 (June 2007): 366–70. https://doi.org/10.1016/j.pain.2007.02.012.
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  - Nackley, Andrea Gail, Kai Soo Tan, Karamarie Fecho, Patrick Flood, Luda Diatchenko, and William Maixner. “Catechol-O-methyltransferase inhibition increases pain sensitivity through activation of both beta2- and beta3-adrenergic receptors.” Pain 128, no. 3 (April 2007): 199–208. https://doi.org/10.1016/j.pain.2006.09.022.
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  - Tan, Kai Soo, Andrea G. Nackley, Kathryn Satterfield, William Maixner, Luda Diatchenko, and Patrick M. Flood. “Beta2 adrenergic receptor activation stimulates pro-inflammatory cytokine production in macrophages via PKA- and NF-kappaB-independent mechanisms.” Cell Signal 19, no. 2 (February 2007): 251–60. https://doi.org/10.1016/j.cellsig.2006.06.007.
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  - Nackley, A. G., S. A. Shabalina, I. E. Tchivileva, K. Satterfield, O. Korchynskyi, S. S. Makarov, W. Maixner, and L. Diatchenko. “Human catechol-O-methyltransferase haplotypes modulate protein expression by altering mRNA secondary structure.” Science 314, no. 5807 (December 22, 2006): 1930–33. https://doi.org/10.1126/science.1131262.
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  - Diatchenko, Luda, Andrea G. Nackley, Gary D. Slade, Kanokporn Bhalang, Inna Belfer, Mitchell B. Max, David Goldman, and William Maixner. “Catechol-O-methyltransferase gene polymorphisms are associated with multiple pain-evoking stimuli.” Pain 125, no. 3 (December 5, 2006): 216–24. https://doi.org/10.1016/j.pain.2006.05.024.
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  - Diatchenko, Luda, Andrea G. Nackley, Gary D. Slade, Roger B. Fillingim, and William Maixner. “Idiopathic pain disorders--pathways of vulnerability.” Pain 123, no. 3 (August 2006): 226–30. https://doi.org/10.1016/j.pain.2006.04.015.
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  - Nackley, Andrea, Luda Diatchenko, and William Maixner. “Perspectives on the genetic basis of opioid-induced hyperalgesia.” Anesthesiology 104, no. 5 (May 2006): 909–10. https://doi.org/10.1097/00000542-200605000-00004.
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  - Hohmann, Andrea G., Mark H. Neely, Jeremiah Piña, and Andrea G. Nackley. “Neonatal chronic hind paw inflammation alters sensitization to intradermal capsaicin in adult rats: a behavioral and immunocytochemical study.” J Pain 6, no. 12 (December 2005): 798–808. https://doi.org/10.1016/j.jpain.2005.07.009.
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  - Fecho, Karamarie, Andrea G. Nackley, Ying Wu, and William Maixner. “Basal and carrageenan-induced pain behavior in Sprague-Dawley, Lewis and Fischer rats.” Physiol Behav 85, no. 2 (June 2, 2005): 177–86. https://doi.org/10.1016/j.physbeh.2005.03.018.
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  - Diatchenko, Luda, Gary D. Slade, Andrea G. Nackley, Konakporn Bhalang, Asgeir Sigurdsson, Inna Belfer, David Goldman, et al. “Genetic basis for individual variations in pain perception and the development of a chronic pain condition.” Hum Mol Genet 14, no. 1 (January 1, 2005): 135–43. https://doi.org/10.1093/hmg/ddi013.
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  - Nackley, A. G., A. M. Zvonok, A. Makriyannis, and A. G. Hohmann. “Activation of cannabinoid CB2 receptors suppresses C-fiber responses and windup in spinal wide dynamic range neurons in the absence and presence of inflammation.” J Neurophysiol 92, no. 6 (December 2004): 3562–74. https://doi.org/10.1152/jn.00886.2003.
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  - Gutierrez, T., A. G. Nackley, M. H. Neely, K. G. Freeman, G. L. Edwards, and A. G. Hohmann. “Effects of neurotoxic destruction of descending noradrenergic pathways on cannabinoid antinociception in models of acute and tonic nociception.” Brain Res 987, no. 2 (October 17, 2003): 176–85. https://doi.org/10.1016/s0006-8993(03)03324-9.
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  - Nackley, A. G., A. Makriyannis, and A. G. Hohmann. “Selective activation of cannabinoid CB(2) receptors suppresses spinal fos protein expression and pain behavior in a rat model of inflammation.” Neuroscience 119, no. 3 (2003): 747–57. https://doi.org/10.1016/s0306-4522(03)00126-x.
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  - Nackley, A. G., R. L. Suplita, and A. G. Hohmann. “A peripheral cannabinoid mechanism suppresses spinal fos protein expression and pain behavior in a rat model of inflammation.” Neuroscience 117, no. 3 (2003): 659–70. https://doi.org/10.1016/s0306-4522(02)00870-9.
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  - Harmon, Jennifer B., Anne E. Sanders, Rebecca S. Wilder, Greg K. Essick, Gary D. Slade, Jane E. Hartung, and Andrea G. Nackley. “Circulating Omentin-1 and Chronic Painful Temporomandibular Disorders.” J Oral Facial Pain Headache 30, no. 3 (n.d.): 203–9. https://doi.org/10.11607/ofph.1608.
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Teaching & Mentoring
Recent Courses
- PHARM 494: Research Independent Study 2022
- PHARM 493: Research Independent Study 2021
- PHARM 494: Research Independent Study 2021
- PHARM 495: Research Independent Study 2021
- NEUROSCI 494: Research Independent Study 2 2020
- PHARM 493: Research Independent Study 2020
- PHARM 494: Research Independent Study 2020
- PHARM 495: Research Independent Study 2020
Scholarly, Clinical, & Service Activities
Outreach & Engaged Scholarship
- Summer Neuroscience Program Mentor. Summer Neuroscience Program. 2020 2020
- Bass Connections Faculty Team Leader. Summer Neuroscience Program Mentor. 2017 2017

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Education, Training, & Certifications

Previous Appointments & Affiliations

Subject Headings

Selected Grants

Selected Publications

Academic Articles

Recent Courses

Outreach & Engaged Scholarship