| Erin Milligan , Ph.D. Assistant Professor Department of Neurosciences |
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The image is a mixed cell population that includes innate immune cells collected from the meninges surrounding the spinal cord. |
Pain regulatory systems, glial cell activation, neuro-immune interactions, spinal cord gene therapy, motor neuron degenerative diseases
Department of Neurosciences
MSC08 4740
1 University of New Mexico
Albuquerque, NM 87131-0001
Email: emilligan@salud.unm.edu
Office Phone: 505-272-8103
Lab Phone: 505-272-8117
Dr. Erin Milligan’s research examines several questions. A primary focus of this lab is applying spinal cord gene therapy approaches to treat chronic neuropathic pain conditions. Glial cells, both astrocytes and microglia, in the spinal cord become activated and are shown to alter normal neuronal signaling that contribute to neuropathic pain. Understanding underlying mechanisms that include glial function in neuropathic pain is leading to novel therapeutic targets to treat neuropathic pain. A part of this research is exploring the delivery of genes to the spinal cord that encode anti-inflammatory cytokines that act to suppress the production and function of glial-neuronal signaling previously implicated in creating and maintaining diverse forms of chronic pain. Both viral and non-viral vectors that deliver genes encoding proteins known to control neuropathic pain are examined. Importantly, this gene delivery approach shows promise for the treatment of clinical pain and is currently being further developed for long-duration pain control. Ongoing studies are examining 1) mechanisms by which these various gene therapy approaches lead to long-lasting pain control, 2) improvement of gene expression with the goal to increase the duration and magnitude of the therapeutic window, and 3) synthetic FDA-approved polymers encapsulating therapeutic genes that may enhance gene expression and therapeutic effects through collaborative efforts with the Department of Chemical and Biomedical Engineering at the University of Colorado in Boulder. However, spinal cord glial cell activation may confer therapeutic value as well. In addition to the focus of the gene therapy for pain control, this lab is beginning to elucidate the effects of cannabinoid compounds for treating chronic inflammatory spinal cord diseases that include neuropathic pain conditions. Lastly, in separate but related studies, we are examining the role of glia in neurodegenerative diseases of the spinal cord. Pain is often part of the repertoire of symptoms that occur in motor neuron degenerative diseases. Chronic glial and peripheral immune cell activation is believed to significantly contribute motor neuron disease progression in people. Ongoing studies are examining the role of spinal cord glia and neuro-immune interactions that lead to chronic neuropathic pain and motor neuron dengeneration. These studies are focused on developing novel drug targets to control clinically relevant neurodegenerative diseases. This research combines multiple approaches with research techniques that include in vivo behavioral assessment with cellular, molecular and polymer-based engineering techniques to deliver therapeutic genes.
Selected Publications:
Milligan, E.D., Ledeboer, A., Sloane E.M . & Watkins, L.R., Glially driven enhancement of pain and its control by anti-inflammatory cytokines. In: Watkins, LR, DeLeo, J and Sorkin, L (Eds). Immune and Glial Regulation of Pain, Seattle: IASP Press, (2007), in press.
Milligan, E.D., Soderquist, R.G., Malone, S.,Mahoney, J.H., Hughes, T.S.,Langer, S.J., Sloane, E.M., Maier, S.F., Leinwand, L.A., Watkins,L.R & Mahoney, M.J. Intrathecal polymer-based interleukin-10 gene delivery for neuropathic pain, Neuron Glia Biology, 2 (2006) 293-308.
Milligan, E.D, Sloane, E.M, Langer, S.J, Hughes, T.S, Jekich, B.M, Frank, M.G., Mahoney, J.H, Levkoff, L.H, Maier, S.F., Cruz, P.E, Flotte, T.R, Johnson, K.W, Mahoney, M. M, Chavez, Leinwand, L.A, Watkins, L.R. Repeated intrathecal injections of plasmid DNA encoding interleukin-10 produce prolonged reversal of neuropathic pain. Pain, (2006),126: 294-308.
Milligan E , Zapata V, Schoeniger D, Chacur M, Green P, Poole S, Martin D, Maier SF, Watkins LR., An initial investigation of spinal mechanisms underlying pain enhancement induced by fractalkine, a neuronally released chemokine, Eur J Neurosci., (2005) 11:2775-82.
Milligan, E.D., Sloane, E.M., Langer, S.J., Cruz, P.E., Chacur, M., Spataro, L. Hammack, S.E., Maier, S.F., Flotte, T.R., Forsayeth, J.R., Leinwand, L.A., Chavez, R. & Watkins, L.R., Controlling neuropathic pain by adeno-associated virus driven production of the anti-inflammatory cytokine, interleukin-10, Molecular Pain, (2005) 1:9.
Milligan, E.D., Langer, S.J., Sloan, E.,M He, L., Wieseler-Frank, J., K. O’Connor, D. Martin, Forsayeth, J.R., Maier, S.F., Johnson, K., Chavez, R.A. Leinwand, L.A. & Watkins, L.R., Controlling pathological pain by adenovirally driven spinal production of the anti-inflammatory cytokine, interleukin-10, Eur. J. Neurosci., (2005) 21:2136-48.
Milligan, E.D., Maier, S.F. & Watkins, L.R., Sciatic inflammatory neuropathy: a new model for studying neuropathic pain of inflammatory origin. In: D. Luo (Ed.) Pain Research: Methods and Protocols; “Methods of Molecular Medicine”, Vol. 99, Humana Press, (2004) pp. 67-89.
Milligan, E.D. , Watkins, L.R., & Maier, S.F., Glial proinflammatory cytokines mediate exaggerated pain states: implications for clinical pain, Seminars in Pain Medicine, 1(3)(2003) 1-13.
Milligan, E.D., Twining, C., Chacur, M., Biedenkap, J., O’Connor, K., Poole, S., Tracey, K., Martin, D., Maier, S.F. & Watkins, L.R., Spinal glia and proinflammatory cytokines mediate mirror-image neuropathic pain, J. Neurosci., (2003) 23:1026-1040.
Milligan, E.D., O’Connor, K.A., Nguyen, K.T., Armstrong, C.B., Twining, C., Gaykema, R.A., Martin, D., Maier, S.F. & Watkins, L.R., Intrathecal HIV-1 envelope glycoprotein gp120 induces enhanced pain states mediated by spinal cord proinflammatory cytokines, J. Neurosci., (2001) 21:2808-2819.
Watkins, L.R., Milligan, E.D. & Maier, S.F., Glial activation: a driving force for pathological pain, Trends in Neuroscience, 24 (2001) 450-455.
