Recent studies indicate that cannabinoids can produce antinociception, particularly in persistent pain conditions, through peripheral mechanisms. This is particularly interesting because targeting peripheral receptors for pain eliminates unwanted side effects associated with receptor activation if the central nervous system. Moreover, it has been suggested that cannabinoids may be more effective in conditions of persistent pain. In the proposed studies we will investigate the ability of cannabinoids to attenuate cancer pain. Cancer pain is a major problem for many patients and is often undermanaged. Using a model of cancer pain in mice in which sarcoma cells are implanted in and around the calcaneous bone, we will determine whether cannabinoids attenuate hyperalgesia when administered at the site of tumor growth (hind paw) and identify the receptor types involved through the use of receptor-selective agonists and antagonists. Mechanisms underlying peripheral cannabinoid antinociception will be investigated in electrophysiological and cellular studies. In Parallel of electrophysiological studies, we will determine if cannabinoids attenuate the sensitization of nociceptors that occurs during tumor growth. We will also investigate cellular events related to cannabinoid signaling that occur during tumor growth. We will determine whether cancer cells modify cannabinoid receptor expression and cannabinoid receptor signaling in primary afferent neurons.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
2R01DA011471-06
Application #
6877367
Study Section
Special Emphasis Panel (ZRG1-IFCN-A (91))
Program Officer
Thomas, David A
Project Start
2000-02-03
Project End
2009-12-31
Budget Start
2005-03-01
Budget End
2005-12-31
Support Year
6
Fiscal Year
2005
Total Cost
$261,625
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Psychiatry
Type
Schools of Medicine
DUNS #
555917996
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
Uhelski, Megan L; Gupta, Kalpna; Simone, Donald A (2017) Sensitization of C-fiber nociceptors in mice with sickle cell disease is decreased by local inhibition of anandamide hydrolysis. Pain 158:1711-1722
Uhelski, Megan L; Khasabova, Iryna A; Simone, Donald A (2015) Inhibition of anandamide hydrolysis attenuates nociceptor sensitization in a murine model of chemotherapy-induced peripheral neuropathy. J Neurophysiol 113:1501-10
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Cain, David M; Vang, Derek; Simone, Donald A et al. (2012) Mouse models for studying pain in sickle disease: effects of strain, age, and acuteness. Br J Haematol 156:535-44
Khasabov, S G; Brink, T S; Schupp, M et al. (2012) Changes in response properties of rostral ventromedial medulla neurons during prolonged inflammation: modulation by neurokinin-1 receptors. Neuroscience 224:235-48

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