Professor, Pharmacology, Anesthesiology & Neurology
- University of Arizona, 1995 (Ph.D.)
- Academy of Medical Education Scholars. 2010-present.
- Learning to Lead, University of Arizona COM 2010-2011.
- Better-Than-Ever Award in Breast Cancer Research 2009-2010.
- Outstanding Teacher in the Neuroscience Block Year I Medical School, 2009 & 2010.
- Dean's List for Excellence in Teaching in the Basic Sciences, Selected by Students, 2006-2009.
- Highlighted Faculty Achievement, University of Arizona, COM, 2008
- Furrow Teaching Award, Excellence in Basic Science Teaching for Medical Students, Selected by Peers, 2006.
- AACC Outstanding Speaker Award (2007-2008) Continuing Educations Program.
- American Pain Society SIG Chair 2006-2009.
- Teaching Award, Human Neuroscience, Best Basic Science Course, Medical Students, Fall 2004 - 2006.
- Academic Keys Who's Who in Medical Sciences Education (WWMSE) 2005.
- Teaching Award, Human Neuroscience, Medical Students, Fall 2003.
- Univ. of Arizona Graduate College Fellowship Fall 1991, Spring 1992, Fall 1992.
- Honors, Graduate School GPA 4.0, Univ. of Arizona, 1991-1995.
- Honorable Mention, National Science Foundation, 1992.
- INRC/CPDD Travel Award, 1992.
- INRC Travel Award 1994-1996.
- ASPET Travel Award, 1991.
- Eugene Pulliman Scholarship, 1986-1990.
- Honorable Mention, 4.0 Years, Univ. of Arizona, 1990, 1991.
- Honors Program, University of Arizona, 1988-1989.
- President's List of Scholars, Honors Program, Phoenix College, 1986-1987.
- mechanisms and pharmacology of acute and chronic models of pain
- neuronal integration in pain pathways
- neurochemical release during conditions of neuropathy
- neuronal plasticity
- antinociceptive synergy between cannabinoids and opioids
- endogenous opioid systems
- sensory neural systems
- opioid tolerance
- activation of cannabionoid receptors
- opioid receptor pharmacology
- novel targets for drug discovery
- bone cancer pain
- migraine and cortical spreading depression
Several types of cancer including breast, prostate and lung often metastasize to the bone where they result in excrutiating amounts of pain and bone destruction. Our goals are to determine what causes such pain and how cancer results in the degradation of the bone.
We are currently studying non-psychoative (non-addictive) cannbinoids for such pain. Opioids, such as morphine and codeine, are currently the medicine of choice for pain relief. Yet, the presence of increased pain requires increasing doses of an opioid to elicit the same degree of pain relief - more pain means a need for more opioid. The increased need for opioid to attain the same level of pain relief has been termed "opioid tolerance".
In addition, clinical reports have described patients being treated with higher and higher doses of opioids for an extended period of time result in the development of unexpected, paradoxical pain (pain in regions unrelated to the original site of injury) due to the opioid itself.
Our current research goal is to understand the neural-mediated mechanism underlying opioid tolerance and opioid-induced pain. Our laboratory is measuring the release of neurotransmitters at the level of the spinal cord in animals treated with opioids. Data suggest that the activation of specific neurons at the level of the brainstem result in the manifestation of increased pain in the presence of opioids.
For these reasons, it appears that opioid antinociceptive tolerance may, in fact, be the result of increased levels of pain elicited by activation of supraspinal pain facilitation mechanisms and enhanced pain neurotransmitter release at the level of the spinal cord.
Furthermore, using microdialysis, we are measuring neurotransmitter release both at the level of the spinal cord and brain in regions responsible for modulating sensory input. Studies are currently being performed to look at how both pharmacological compounds as well as antisense oligodeoxynucleotide to endogenous proteins alter the behavioral and neurotransmitter response.
The ultimate goals of this research are to identify novel pharmacotherapies for the treatment of pain, further understand the physiological basis of pain, and discover how the nervous system adapts to persistent sensory input from specific types of nerve fibers.
Ondoua-Lozano AN, KE Hanlon, TM Largent-Milnes, A Chandramouli, M Owusu-Ankomah, AP Bloom, JM Jimenez-Andrade, T King, F Porreca, TP Malan Jr., MA Nelson, PW Mantyh, TW Vanderah: Disease Modification of Breast Cancer by Cannabinoid CB2 Receptor Agonists. (In Review), Nature Med, 2011.
Largent-Milnes TM, T Yamamoto, P Nair, VJ Hruby, J Lai, F Porreca, TW Vanderah: Spinal or systemic TY005, a peptidic opioid agonist/neurokinin 1 antagonist, attenuates pain with reduced tolerance, British Journal of Pharmacology, 161(5): 968-1001, 2010.
Lozano-Ondoua AN, C Wright, A Vardanyan, T King, TM Largent-Milnes, M Nelson, JM Jimenez-Andrade, PW Mantyh, TW Vanderah: Cannabinoid 2 Receptors Attenuate Pain and Maintain Bone Structure In a Murine Model of Bone Cancer. Life Sciences, 86(17-18): 646-653, 2010.
King T, L Vera-Portocarrero, T Gutierrez, TW Vanderah, G Dussor, J Lai, HL Fields, F Porreca: Unmasking the tonic-aversive state in neuropathic pain. Nat Neurosci, 12(11):1364-6, 2009.
Fioravanti B, M De Felice, CL Stucky, KA Medler, MC Luo, LR Gardell, M Ibrahim, TP Malan Jr, HI Yamamura, MH Ossipov, T King,J Lai, F Porreca, TW Vanderah: Constitutive activity at the cannabinoid CB1 receptor is required for behavioral response to noxious chemical stimulation of TRPV1: antinociceptive actions of CB1 inverse agonists. J Neuroscience, 28(45):11593-602, 2008.
Edelmayer RM, TW Vanderah, L Majuta, ET Zhang, B Fioravanti, M De Felice, JG Chichorro, MH Ossipov, T King, J Lai, SH Kori, AC Nelsen, KE Cannon, MM Heinricher, F Porreca:. Medullary pain facilitating neurons mediate allodynia in headache-related pain. Annals Neurol, 65(2):184-193, 2009.
Konstantina Zuber (MSRP 2007): "Identify the neurotransmitters in RVM and spinal cord that are mediating pain."
Ryan Burkland (MSRP 2008): "Cannabinoids 2 and bone fracture pain and bone healing."
Gerald Moulton (MSRP 2009): "Does the bifunctional peptide TY027 demonstrate a reduced side effect profile including reward, physical dependence, and nausea after central or systemic administration?"
David Skinner (MSRP 2010): "Cutaneous Allodynia in a Model of Cortical Spreading Depression in Freely Moving Rats"
Alexander Podolsky (MSRP 2011): "Attenuation of Pain Without Tolerance and Diminished Reward Behavior with an Opioid Agonist/Neurokinin 1 Antagonist."
Christopher Luckow (MSRP 2012): "A Study of the Effects of Specific Drugs on CB2 Receptors in Breast Cancer Induced Bone Pain."
Scott Wallace (MSRP 2012): "Novel Efficacious Antinociceptive Opioids Without Addictive, Constipative, or Emetic Properties in Animals."
Thomas Lotina (MSRP 2014): "Testing of Novel CB2 Agonists in Models of Acute and Chronic Pain."
Ryan Bruhns (MSRP 2016): "Remote Ischemic Conditioning Mitigation of Secondary Brain Injury in a Mouse TBI Model"
Ricarda Ayala (MSRP 2017): "Sustained Morphine in Model of Bone Cancer Pain Causes Increase in Bone Loss"
Michael Gaub (MSRP 2017): "Evaluating the Efficacy of Ang-(1-7) Derivatives for Treatment of TBI-induced Cognitive Impairment Using MRI-Based Imaging Modalities"
Alexander Podolsky (RDT 2014): "Attenuation of Pain in Various Opioid Derivates and Adrenergic Compounds"
- Heather Johnson, Amphitheater High School, 2000
- ShanaSue Shallenberger, Flowing Wells High School, 2001
- Teressa Riney, University High School, 2002
- Patrick Gorman, Flowing Wells High School, 2003
- Maria "Terri" Irigoyen, Sunnyside High School, 2004
- Aimee Uwimana, Cesar Chavez High School, 2005
- Alberto Antonio Romero, Nogales High School, 2010
- Karen Sanudo, Tevor G Browne High School, 2012
- Phillip Alvarez, Pueblo Magnet High School, 2013
- Mayra Mena, Purblo High School, 2015
- Mara Steeber, Mountain View High School, 2015
- Anna Larson, Saguaro High School, 2016
- Angela Lozano, Kofa High School, 2016
- Lucas Perry-Johnson, Catalina Magnet High School, 2017