The PI's preclinical research program seeks to understand how activation of peripheral immune cells and central nervous system glia (microglia and astrocytes) triggers a cascade of events leading to neuronal activation, pathological pain states, and dysregulation of the clinically relevant effects of analgesic drugs. The current research focus is directly relevant to her long-term goals of understanding (a) immune-neuralbidirectional interactions, and (b) pain modulation systems. The proposed project is a request for a K05 award for the PI to focus on programmatic investigations of pathological pain states. The currently funded projects include: (a) Immune/glial mediation of exaggerated pain states;NIDA K02 (Watkins PI;6/03-5/08;DA015642);(b) Pain control via spinal interleukin-10 gene therapy;NIDA CEBRA Phase II (R01;Milligan PI;Watkins coPI;09/04-09/09;DA018156);(c) Pain facilitation via neuron-to-glia signaling;NIDA R01 (Watkins PI;3/05-12/09;DA017670);(d) Opioid analgesics: modulation.of trigeminal &Spinal glial activation;NIDCR R01 (Watkins PI;7/06-4/11;DE017782);(e) Exploration of AV411, a blood brain barrier permeable glial activation inhibitor;Avigen (Watkins Pl;1/06-12/08);(f) Development of rat models to assess potential glial involvement in migraine;GlaxoSmithKline (Watkins PI;1/07-12/09);(g) Translation from rats to humans: are chronic pain states in humans associated with glial activation in spinal cord and/or brain?;American Fibromyalgia Syndrome Association (Watkins CD Boulder PI;open ended small grant);(h) Human spinal cord glial cytokines &chronic pain NIAMSD R01 (Lorton, PI;Watkins, coPI;7/07-6/12;AR054647);&(i) mRNA &protein analyses of spinal cord &CSF from spinal cord injury patients with vs. without chronic pain;Craig Spinal Cord Injury Treatment &Rehabilitation Hospital (Watkins CU Boulder PI;9/07-open ended small grant). In addition, projects under review include: (j) Development of opioid therapeutic approaches that fail to activate glia;Covidien (Watkins PI);(k) Exploring the potential of glia for regulating clinically relevant opioid actions, R01 proposal (Watkins PI);and (I) Exploiting viral mimicry to develop new therapies for treating neuropathic pain, R21 Proposal (Leinwand PI;Watkins coPI). Thus this is an active &diverse research program exploring multiple levels of analyses at the forefront of pain research. All of these projects are focused on understanding immune/glial regulation of pain and analgesic actions. Beyond this extensive research program, the PI is committed to education of the scientific and lay communities on these topics via review articles and chapters and invited talks, and the mentorship of young investigators.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Research Scientist Award (K05)
Project #
Application #
Study Section
Human Development Research Subcommittee (NIDA)
Program Officer
Purohit, Vishnudutt
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Colorado at Boulder
Schools of Arts and Sciences
United States
Zip Code
Corrigan, Frances; Wu, Yue; Tuke, Jonathan et al. (2015) Alcohol-induced sedation and synergistic interactions between alcohol and morphine: a key mechanistic role for Toll-like receptors and MyD88-dependent signaling. Brain Behav Immun 45:245-52
Loram, Lisa C; Strand, Keith A; Taylor, Frederick R et al. (2015) Adenosine 2A receptor agonism: A single intrathecal administration attenuates motor paralysis in experimental autoimmune encephalopathy in rats. Brain Behav Immun 46:50-4
Grace, Peter M; Maier, Steven F; Watkins, Linda R (2015) Opioid-induced central immune signaling: implications for opioid analgesia. Headache 55:475-89
Grace, P M; Ramos, K M; Rodgers, K M et al. (2014) Activation of adult rat CNS endothelial cells by opioid-induced toll-like receptor 4 (TLR4) signaling induces proinflammatory, biochemical, morphological, and behavioral sequelae. Neuroscience 280:299-317
Grace, Peter M; Strand, Keith A; Maier, Steven F et al. (2014) Suppression of voluntary wheel running in rats is dependent on the site of inflammation: evidence for voluntary running as a measure of hind paw-evoked pain. J Pain 15:121-8
Rodgers, Krista M; Deming, Yuetiva K; Bercum, Florencia M et al. (2014) Reversal of established traumatic brain injury-induced, anxiety-like behavior in rats after delayed, post-injury neuroimmune suppression. J Neurotrauma 31:487-97
Ellis, Amanda; Wieseler, Julie; Favret, Jacob et al. (2014) Systemic administration of propentofylline, ibudilast, and (+)-naltrexone each reverses mechanical allodynia in a novel rat model of central neuropathic pain. J Pain 15:407-21
Hutchinson, Mark R; Watkins, Linda R (2014) Why is neuroimmunopharmacology crucial for the future of addiction research? Neuropharmacology 76 Pt B:218-27
Theberge, Florence R; Li, Xuan; Kambhampati, Sarita et al. (2013) Effect of chronic delivery of the Toll-like receptor 4 antagonist (+)-naltrexone on incubation of heroin craving. Biol Psychiatry 73:729-37
Bastos, Leandro F S; Godin, Adriana M; Zhang, Yingning et al. (2013) A minocycline derivative reduces nerve injury-induced allodynia, LPS-induced prostaglandin E2 microglial production and signaling via toll-like receptors 2 and 4. Neurosci Lett 543:157-62

Showing the most recent 10 out of 50 publications