Broadly stated, this research project has two goals. First, I plan to investigate behavioral, neurophysiological, neuroanatomical, and neurochemical aspects of analgesia produced by focal electrical stimulation of the brain and to compare this phenomenon to analgesia produced by morphine micro-injection. Some of the specific goals subsumed under this project include: 1) To precisely describe the neuroanatomical pathways utilized and the ultimate sites and mechanisms of analgesic action. 2) To further describe the involvement of endogenous opiate substances in analgesia resulting from certain environmental manipulations. 3) To examine the functional neurochemistry of narcotic and non-narcotic analgesia systems. 4) To examine behavioral manifestations of tolerance and physical dependence to the analgesia produced by these procedures and to relate these findings to the general problem of opiate addiction. 5) To be able to suggest new and practical treatment procedures for difficult or intractable pain syndromes in man. Secondly, I proposed to identify, employing electrophysiological techniques, brain areas with behaviorally significant involvement in pain perception. Stimulation-produced analgesia, morphine analgesia, and behavioral manipulation of pain perception will be utilized as tools to achieve this goal.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA000576-13
Application #
3206799
Study Section
(DABA)
Project Start
1973-06-01
Project End
1989-08-31
Budget Start
1988-01-01
Budget End
1989-08-31
Support Year
13
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Virginia Commonwealth University
Department
Type
Schools of Medicine
DUNS #
City
Richmond
State
VA
Country
United States
Zip Code
23298
Mayer, D J; Kellstein, D E (1992) Cholecystokinin and opiate interactions. Clin Neuropharmacol 15 Suppl 1 Pt A:477A-478A
Mao, J; Coghill, R C; Kellstein, D E et al. (1992) Calcitonin gene-related peptide enhances substance P-induced behaviors via metabolic inhibition: in vivo evidence for a new mechanism of neuromodulation. Brain Res 574:157-63
Leshem, M; Frenk, H; Coghill, R C et al. (1991) Paradoxical opiate specific paralytic effects of high doses of intracerebroventricular etorphine and fentanyl in rats. Pharmacol Biochem Behav 38:475-8
Kellstein, D E; Mayer, D J (1991) Spinal co-administration of cholecystokinin antagonists with morphine prevents the development of opioid tolerance. Pain 47:221-9
Kellstein, D E; Price, D D; Mayer, D J (1991) Cholecystokinin and its antagonist lorglumide respectively attenuate and facilitate morphine-induced inhibition of C-fiber evoked discharges of dorsal horn nociceptive neurons. Brain Res 540:302-6
Bossut, D F; Huang, Z S; Sun, S L et al. (1991) Electroacupuncture in rats: evidence for naloxone and naltrexone potentiation of analgesia. Brain Res 549:36-46
Bossut, D F; Mayer, D J (1991) Electroacupuncture analgesia in rats: naltrexone antagonism is dependent on previous exposure. Brain Res 549:47-51
Bossut, D F; Mayer, D J (1991) Electroacupuncture analgesia in naive rats: effects of brainstem and spinal cord lesions, and role of pituitary-adrenal axis. Brain Res 549:52-8
Frenk, H; Miller, J; Johannessen, J N et al. (1990) Spinal paralysis and catalepsy induced by intrathecal injection of opioid agonists. Pharmacol Biochem Behav 36:243-7
Kellstein, D E; Mayer, D J (1990) Chronic administration of cholecystokinin antagonists reverses the enhancement of spinal morphine analgesia induced by acute pretreatment. Brain Res 516:263-70

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