The long term objective of this project is to determine the neural mechanisms of opioid inhibition of nociception at the spinal cord level and compare this effect with the opioid inhibition of nociception at the brainstem level. The ultimate goal is a better understanding of the mechanisms of the opioid blockade of pain with the hope that this understanding will lead to the rational development of analgesic drugs and other treatments which are more selective, less addicting and lead to fewer side effects. The development of epidural analgesics is an example of the treatments which a more thorough understanding of the opioid mechanisms has led to.
The specific aims of the next grant period are to: l) determine the effects of activating and inactivating specific opioid receptor subtypes on the responses of extra- and intracellularly recorded lamina I and II neurons. 2) determine the site of action of different opioid receptor subtypes in lamina I and II (pre- vs. postsynaptic). 3) determine the relationship of activating specific opioid receptor subtypes on nociceptive behavior in the rat and correlate these effects with the production of FOS onco-protein at both the spinal and brainstem level. 4) determine at which site, spinal cord or brainstem, specific opioid agonists are most effective when applied systemically. A series of in vivo extra and intracellular recording studies is proposed in anesthetized cats combined with microiontophoresis and intrathecal and systemic application of opioids to address the first specific aim. In vitro whole cell patch clamping experiments in spinal cord slices are proposed to address specific aim 2. Whole animal behavioral studies in rats combined with immunocytochemistry of FOS protein are proposed to address specific aims 3 and 4.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA004420-07
Application #
2117189
Study Section
Drug Abuse Biomedical Research Review Committee (DABR)
Project Start
1987-04-01
Project End
1996-07-31
Budget Start
1994-09-01
Budget End
1995-07-31
Support Year
7
Fiscal Year
1994
Total Cost
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Physiology
Type
Schools of Medicine
DUNS #
078861598
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Vincler, M; Maixner, W; Vierck, C J et al. (2001) Estrous cycle modulation of nociceptive behaviors elicited by electrical stimulation and formalin. Pharmacol Biochem Behav 69:315-24
Schneider, S P; Eckert 3rd, W A; Light, A R (1998) Opioid-activated postsynaptic, inward rectifying potassium currents in whole cell recordings in substantia gelatinosa neurons. J Neurophysiol 80:2954-62
Robinson, G A (1996) Changes in the expression of transcription factors ATF-2 and Fra-2 after axotomy and during regeneration in rat retinal ganglion cells. Brain Res Mol Brain Res 41:57-64
Alvarez, F J; Taylor-Blake, B; Fyffe, R E et al. (1996) Distribution of immunoreactivity for the beta 2 and beta 3 subunits of the GABAA receptor in the mammalian spinal cord. J Comp Neurol 365:392-412
Bove, G M; Light, A R (1995) Calcitonin gene-related peptide and peripherin immunoreactivity in nerve sheaths. Somatosens Mot Res 12:49-57
Robinson, G A (1995) Axotomy-induced regulation of c-Jun expression in regenerating rat retinal ganglion cells. Brain Res Mol Brain Res 30:61-9
Willcockson, H H; Taylor-Blake, B; Light, A R (1995) Induction of fos-like immunoreactivity by electrocutaneous stimulation of the rat hindpaw. Somatosens Mot Res 12:151-61
Bove, G M; Light, A R (1995) Unmyelinated nociceptors of rat paraspinal tissues. J Neurophysiol 73:1752-62
Slugg, R M; Light, A R (1994) Spinal cord and trigeminal projections to the pontine parabrachial region in the rat as demonstrated with Phaseolus vulgaris leucoagglutinin. J Comp Neurol 339:49-61
Alvarez, F J; Kavookjian, A M; Light, A R (1993) Ultrastructural morphology, synaptic relationships, and CGRP immunoreactivity of physiologically identified C-fiber terminals in the monkey spinal cord. J Comp Neurol 329:472-90

Showing the most recent 10 out of 16 publications