Patrick W Mantyh, PhD, JD

Professor of Pharmacology
Phone Number: 
(520) 626-0743
FAX: 
(520) 626-4182

UACC Information

UACC Organizational Unit: 
Professional Bio: 

More than 10 million people are diagnosed with cancer every year and by 2020 it is estimated that 15 million new cases will be diagnosed each year. In 2005 cancer caused 7.6 million deaths world-wide. In the United States, it is estimated that cancer has now eclipsed heart disease as the leading cause of death as one in four US deaths are cancer related.

Despite the increasing prevalence of cancer, improvements in the detection and treatment of most types of cancers have resulted in significantly increased survival rates. For many patients, pain is the first sign of cancer and the majority of individuals will experience moderate to severe pain during the course of their disease and into survivorship. Interestingly, several therapies that are given to control pain also appear to have significant effects on tumor growth and metastasis and thus may not only relieve pain but increase survival of cancer patients.

Dr. Mantyh's lab looks to understand why cancer cells preferentially metastasize to specific organs such as the bone, what role nerves that innervate the bone play in tumor metastasis to bone, and to develop a mechanism-based understanding and therapies to prevent the metastasis of tumors to bone, the growth of tumors in bone and reduce the severe pain that tumor metastases can cause. Findings from these studies may provide mechanistic insight and allow the development of new therapies, which may improve the quality of life and survival of cancer patients.

Dr. Mantyh's lab developed the first animal models of bone cancer pain. Using these models they have identified some of the key mechanisms that drive bone cancer pain. These data and collaborations with biotech and pharmaceutical companies has results in several therapies (bisphosphonates, Denosumab, anti-NGF, Substance P saporin, endothelin antagonists) that have either been approved or are in clinical trials for treating bone cancer pain and disease progression.  Recently, their lab has investigated whether blockade of nerve sprouting can attenuate pain, tumor growth and metastasis that contribute to drug resistance and metastasis of tumors growing in bone. Currently, the lab is also exploring cross talk between sensory and sympathetic nerve fibers in the bone as it has been suggested that the interaction between nerve and cancer cells may contribute to incurable nature of tumors once they have metastasized to bone

See Dr. Mantyh's full bio at the UA Department of Pharmacology.

Research Information

Research Program: 
Cancer Biology
Member Status: 
Research Member
Selected Publications: 
  1. Mantyh PW, Allen CJ, Ghilardi JR, Rogers SD, Mantyh CR, Liu H, Basbaum AI, Vigna SR, Maggio JE. Rapid endocytosis of a G protein-coupled receptor: substance P evoked internalization of its receptor in the rat striatum in vivo. Proc Natl Acad Sci U S A. 1995 Mar 28;92(7):2622-6. PubMed PMID: 7535928; PubMed Central PMCID: PMC42270.
  2. Mantyh PW, DeMaster E, Malhotra A, Ghilardi JR, Rogers SD, Mantyh CR, Liu H, Basbaum AI, Vigna SR, Maggio JE. Receptor endocytosis and dendrite reshaping in spinal neurons after somatosensory stimulation. Science. 1995 Jun 16;268(5217):1629-32. PubMed PMID: 7539937.
  3. Liu H, Mantyh PW, Basbaum AI. NMDA-receptor regulation of substance P release from primary afferent nociceptors. Nature. 1997 Apr 17;386(6626):721-4. PubMed PMID: 9109489.
  4. Abbadie C, Trafton J, Liu H, Mantyh PW, Basbaum AI. Inflammation increases the distribution of dorsal horn neurons that internalize the neurokinin-1 receptor in response to noxious and non-noxious stimulation. J Neurosci. 1997 Oct 15;17(20):8049-60. PubMed PMID: 9315923.
  5. Mantyh PW, Rogers SD, Honore P, Allen BJ, Ghilardi JR, Li J, Daughters RS, Lappi DA, Wiley RG, Simone DA. Inhibition of hyperalgesia by ablation of lamina I spinal neurons expressing the substance P receptor. Science. 1997 Oct 10;278(5336):275-9. PubMed PMID: 9323204.
  6. Cao YQ, Mantyh PW, Carlson EJ, Gillespie AM, Epstein CJ, Basbaum AI. Primary afferent tachykinins are required to experience moderate to intense pain. Nature. 1998 Mar 26;392(6674):390-4. PubMed PMID: 9537322.
  7. Mantyh PW, Hunt SP. Hot peppers and pain. Neuron. 1998 Oct;21(4):644-5. PubMed PMID: 9808445.
  8. Nichols ML, Allen BJ, Rogers SD, Ghilardi JR, Honore P, Luger NM, Finke MP, Li J, Lappi DA, Simone DA, Mantyh PW. Transmission of chronic nociception by spinal neurons expressing the substance P receptor. Science. 1999 Nov 19;286(5444):1558-61. PubMed PMID: 10567262.
  9. Schwei MJ, Honore P, Rogers SD, Salak-Johnson JL, Finke MP, Ramnaraine ML, Clohisy DR, Mantyh PW. Neurochemical and cellular reorganization of the spinal cord in a murine model of bone cancer pain. J Neurosci. 1999 Dec 15;19(24):10886-97. PubMed PMID: 10594070.
  10. Honore P, Rogers SD, Schwei MJ, Salak-Johnson JL, Luger NM, Sabino MC, Clohisy DR, Mantyh PW. Murine models of inflammatory, neuropathic and cancer pain each generates a unique set of neurochemical changes in the spinal cord and sensory neurons. Neuroscience. 2000;98(3):585-98. PubMed PMID: 10869852.
  11. Sevcik MA, Ghilardi JR, Peters CM, Lindsay TH, Halvorson KG, Jonas BM, Kubota K, Kuskowski MA, Boustany L, Shelton DL, Mantyh PW. Anti-NGF therapy profoundly reduces bone cancer pain and the accompanying increase in markers of peripheral and central sensitization. Pain. 2005 May;115(1-2):128-41. PubMed PMID: 15836976.
  12. Mantyh PW. Cancer pain and its impact on diagnosis, survival and quality of life. Nat Rev Neurosci. 2006 Oct;7(10):797-809. PubMed PMID: 16988655.
  13. Honore P, Luger NM, Sabino MA, Schwei MJ, Rogers SD, Mach DB, O'keefe PF, Ramnaraine ML, Clohisy DR, Mantyh PW. Osteoprotegerin blocks bone cancer-induced skeletal destruction, skeletal pain and pain-related neurochemical reorganization of the spinal cord. Nat Med. 2000 May;6(5):521-8. PubMed PMID: 10802707.
  14. Mantyh PW, Clohisy DR, Koltzenburg M, Hunt SP. Molecular mechanisms of cancer pain. Nat Rev Cancer. 2002 Mar;2(3):201-9. PubMed PMID: 11990856.
  15. Sevcik MA, Luger NM, Mach DB, Sabino MA, Peters CM, Ghilardi JR, Schwei MJ, Röhrich H, De Felipe C, Kuskowski MA, Mantyh PW. Bone cancer pain: the effects of the bisphosphonate alendronate on pain, skeletal remodeling, tumor growth and tumor necrosis. Pain. 2004 Sep;111(1-2):169-80. PubMed PMID: 15327821.
  16. Ghilardi JR, Röhrich H, Lindsay TH, Sevcik MA, Schwei MJ, Kubota K, Halvorson KG, Poblete J, Chaplan SR, Dubin AE, Carruthers NI, Swanson D, Kuskowski M, Flores CM, Julius D, Mantyh PW. Selective blockade of the capsaicin receptor TRPV1 attenuates bone cancer pain. J Neurosci. 2005 Mar 23;25(12):3126-31. PubMed PMID: 15788769.
  17. Castañeda-Corral G, Jimenez-Andrade JM, Bloom AP, Taylor RN, Mantyh WG, Kaczmarska MJ, Ghilardi JR, Mantyh PW. The majority of myelinated and unmyelinated sensory nerve fibers that innervate bone express the tropomyosin receptor kinase A. Neuroscience. 2011 Mar 31;178:196-207. PubMed PMID: 21277945; PubMed Central PMCID: PMC3078085.
  18. Ghilardi JR, Freeman KT, Jimenez-Andrade JM, Mantyh WG, Bloom AP, Bouhana KS, Trollinger D, Winkler J, Lee P, Andrews SW, Kuskowski MA, Mantyh PW. Sustained blockade of neurotrophin receptors TrkA, TrkB and TrkC reduces non-malignant skeletal pain but not the maintenance of sensory and sympathetic nerve fibers. Bone. 2011 Feb;48(2):389-98. PubMed PMID: 20854944; PubMed Central PMCID: PMC3020250.
  19. Mantyh WG, Jimenez-Andrade JM, Stake JI, Bloom AP, Kaczmarska MJ, Taylor RN, Freeman KT, Ghilardi JR, Kuskowski MA, Mantyh PW. Blockade of nerve sprouting and neuroma formation markedly attenuates the development of late stage cancer pain. Neuroscience. 2010 Dec 1;171(2):588-98. PubMed PMID: 20851743; PubMed Central PMCID: PMC2992976.
  20. Jimenez-Andrade JM, Martin CD, Koewler NJ, Freeman KT, Sullivan LJ, Halvorson KG, Barthold CM, Peters CM, Buus RJ, Ghilardi JR, Lewis JL, Kuskowski MA, Mantyh PW. Nerve growth factor sequestering therapy attenuates non-malignant skeletal pain following fracture. Pain. 2007 Dec 15;133(1-3):183-96. PubMed PMID: 17693023.
Collaborative Research: 
Ongoing:
2R01 NS023970-26A1             (Mantyh, PI)                                       04/01/87-02/29/20
NIH/NINDS
Peripheral Nociceptors in Persistent Pain
This project will focus on exploring the mechanisms that drive bone fracture pain / bone healing. If successful, this proposal has the potential to fundamentally transform our understanding of skeletal pain and how we treat and prevent age-related pain and bone fractures.
Role: PI
 
5R01 CA157449-05                 (Mantyh, PI)                                       07/01/11-05/31/16
NIH/NCI
Metastatic Prostate Cancer-induced Bone Pain
The overarching hypothesis is that the earlier preventive blockade of the NGF/TrkA pathway is initiated, the more effectively the pathological nerve changes and pain can be controlled. If correct, data from this project may fundamentally change our understanding and treatment of prostate cancer-induced bone pain.
Role: PI
 
5R01 CA154550-05                 (Mantyh, PI)                                       05/01/11-04/30/16
NIH/NCI
Preventive Analgesia for Bone Cancer Pain
The overarching hypothesis is that the earlier administration of anti-NGF or TrkA blockade is begun, the more likely these therapies will block tumor-induced nerve sprouting, neuroma formation, inappropriate up-regulation of ion channels, and pain. If correct, data generated from this project has the potential to fundamentally change our understanding of the mechanisms that drive bone cancer pain and promote the use of preventive analgesia for managing bone cancer pain.
Role: PI

Professional Information

Positions and Honors: 
Positions:
2007-present  Professor of Pharmacology, University of Arizona, Department of Pharmacology, Tucson, AZ & Member, University of Arizona Cancer Center
2007-2011     Senior Career Research Scientist, Minneapolis VAMC, Minneapolis, MN
1998–2007     Professor, University of Minnesota, Neuroscience, Minneapolis, MN
1997-2007     Professor, University of Minnesota , Department of Diagnostic and Biological Sciences, Minneapolis, MN
1996-2007     Professor, University of Minnesota, Department of Psychiatry, Minneapolis, MN
1991-2011     Director of Imaging Core, VAMC, Minneapolis, MN
1989-2007     Research Career Scientist, VAMC, Minneapolis, MN
1989-1996     Associate Professor, University of Minnesota , Dept. of Psychiatry, Minneapolis
1988-1989     Associate Professor, University of California, Los Angeles
1984-1988     Assistant Professor, University of California, Los Angeles
1982-1984     Postdoctoral Fellow, Cambridge University
1981-1982     Postdoctoral Fellow, NASA, Biomedical Division
1979-1981     Predoctoral Fellow, University of California, San Francisco
1978-1979     Predoctoral Fellow, University of California, San Francisco
1977-1978     Predoctoral Fellow, University of California, San Francisco
1974-1976     Part-Time Research Assistant, University of Wisconsin, Madison
 
Honors:
2014   Distinguished Keynote Speaker, Japanese Palliative Care and Pain Society, Kobe, Japan
2013   Taiwanese Medal for Pain Research, Taiwan Pain Society
2009   Excellence Award for Pain Research at 20th Annual Meeting, Irish Pain Society
2009   Distinguished Speaker, 1st Annual Anesthesiology Research Day, University of Pittsburgh
2008   Keynote Speaker for the 30th Anniversary of the Society, Australian Pain Society
2006   Patrick Wall Award, New Zealand Pain Society
2005   Patrick Wall Medal, The British Pain Society
2005   John J. Bonica Award, Eastern Pain Association
2005   20th Annual Gunn-Loke Award in Pain Research, University of Washington
2004   Benjamin G. Covino Memorial Award for Pain Research, Harvard University
2001   NINDS, Jacob Javits Investigators Award
2000   American Pain Society, Fredrick Kerr Award
1985   Fellow, Alfred P. Sloan Award
1984   Fellow, Smith, Kline, & Beckman Award
1982   Postdoctoral Fellowship, National Institutes of Health
1981   Postdoctoral Fellowship, National Research Council
1979   Predoctoral NASA Fellowship, NASA, Moffett Palo Alto
1976   Anatomy Predoctoral Fellowship, University of California San Francisco
Other Experience and Professional Memberships/Affiliations: 
Member, Society for Neuroscience
Member, International Brain Research Organization
Member, International Association for the Study of Pain
Member, American Society for Neurochemistry
Member, American Pain Society
Member, American Association for the Advancement of Science
2008-2010    Member, VA Research, Rehabilitation and Development Study Section
2007-Member  University of Arizona Cancer Center
2004-2007    Chair, NINDS NSD-C Study Section
1999-2004    Member, NINDS NSD-C Study Section

Academic Information

Post Doctoral: 
Cambridge University, Cambridge UK
Doctorate: 
University of California, San Francisco; JD, William Mitchell College of Law, St. Paul
Undergraduate School: 
University of Wisconsin, Madison