One in three Americans suffer from chronic pain. Available therapeutic interventions show limited efficacy and are plagued by adverse side effects (e g, altered mental status, sedation, nausea) that accompany systemic routes of drug administration Novel pharmacotherapies that specifically target the periphery therefore represent an alternative strategy for managing pain in the absence of unwanted central side-effects. Activation of a cannabinoid system- a nonopioid system that acts through a marijuana-like mechanism- in the periphery attenuates nociceptive responding The proposed research combines correlative behavioral and neurophysiological approaches to examine the functional consequences of peripheral cannabinoid actions on nociceptive transmission in vivo The use of subtype selective competitive antagonists and high affinity agonists provide the pharmacological tools required to study peripheral cannabinoid actions The proposed work uses a rat model of inflammation to test the hypothesis that a peripheral cannabinoid mechanism suppresses responses evoked by natural cutaneous stimulation in physiologically identified neurons of the spinothalamic tract Behavioral correlates for the electrophysiological studies will be established by assessing peripheral cannabinoid modulation of responsiveness to thermal and punctate mechanical stimulation under similar conditions The consequences of peripheral inflammation on axonal transport of cannabinoid receptors to peripheral nerve terminals is evaluated The development of effective pharmacotherapies for pain that are non-toxic, non-addicting and devoid of side-effects is likely to have a profound impact by improving quality of human life and reducing socioeconomic costs associated with inadequate pain management.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA014022-02
Application #
6665100
Study Section
Integrative, Functional and Cognitive Neuroscience 8 (IFCN)
Program Officer
Thomas, David A
Project Start
2002-09-30
Project End
2005-08-31
Budget Start
2003-09-01
Budget End
2004-08-31
Support Year
2
Fiscal Year
2003
Total Cost
$139,570
Indirect Cost
Name
University of Georgia
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
004315578
City
Athens
State
GA
Country
United States
Zip Code
30602
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Rahn, E J; Makriyannis, A; Hohmann, A G (2007) Activation of cannabinoid CB1 and CB2 receptors suppresses neuropathic nociception evoked by the chemotherapeutic agent vincristine in rats. Br J Pharmacol 152:765-77
Hohmann, A G (2007) Inhibitors of monoacylglycerol lipase as novel analgesics. Br J Pharmacol 150:673-5
Hohmann, Andrea G; Suplita 2nd, Richard L (2006) Endocannabinoid mechanisms of pain modulation. AAPS J 8:E693-708
Connell, Katherine; Bolton, Nathan; Olsen, Daniel et al. (2006) Role of the basolateral nucleus of the amygdala in endocannabinoid-mediated stress-induced analgesia. Neurosci Lett 397:180-4
Suplita 2nd, Richard L; Gutierrez, Tannia; Fegley, Darren et al. (2006) Endocannabinoids at the spinal level regulate, but do not mediate, nonopioid stress-induced analgesia. Neuropharmacology 50:372-9
LoVerme, Jesse; Russo, Roberto; La Rana, Giovanna et al. (2006) Rapid broad-spectrum analgesia through activation of peroxisome proliferator-activated receptor-alpha. J Pharmacol Exp Ther 319:1051-61
Hohmann, Andrea G; Neely, Mark H; Pina, Jeremiah et al. (2005) Neonatal chronic hind paw inflammation alters sensitization to intradermal capsaicin in adult rats: a behavioral and immunocytochemical study. J Pain 6:798-808
Nackley, A G; Zvonok, A M; Makriyannis, A et al. (2004) Activation of cannabinoid CB2 receptors suppresses C-fiber responses and windup in spinal wide dynamic range neurons in the absence and presence of inflammation. J Neurophysiol 92:3562-74
Hohmann, Andrea G; Farthing, Jesse N; Zvonok, Alexander M et al. (2004) Selective activation of cannabinoid CB2 receptors suppresses hyperalgesia evoked by intradermal capsaicin. J Pharmacol Exp Ther 308:446-53

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