K. J. Powell

K. Jhamandas

R. Quirion

T. Trang

The Scientific World Journal

Crossref

4th International Meeting on Calcitonin Gene-Related Peptide (CGRP) 
TheScientificWorld (2001) 1(S1), 21 
ISSN 1532-2246; DOI 10.1100/tsw.2001.433 
  
THE ROLE OF CGRP IN THE DEVELOPMENT OF MORPHINE TOLERANCE AND 
PHYSICAL DEPENDENCE 
  
K.J. Powell, T. Trang, R. Quirion1, and K. Jhamandas 
Department of Pharmacology and Toxicology, Queen’s University, Kingston, Ontario, Canada; 
Douglas Hospital Research Centre, McGill University, Verdun, Quebec, Canada 
  
Chronic morphine treatment produces adaptive changes in spinal neurons that reduce opioid 
action and lead to the development of morphine tolerance and physical dependence. The spinal 
neuropeptide calcitonin gene-related peptide (CGRP) has been implicated in these phenomena. 
We have shown that both spinal and systemic chronic morphine treatment induces an increase in 
CGRP in the dorsal horn of the spinal cord and that an acute naloxone challenge depletes CGRP 
from spinal primary afferents. The CGRP receptor antagonist, CGRP8-37, blocks the development 
of tolerance and reverses established tolerance. It also prevents and reverses changes in spinal 
CGRP expression associated with tolerance. A nonpeptide CGRP receptor antagonist 
BIBN4096BS was also effective, although less potent than CGRP8-37. Additionally, CGRP8-37 
reduces the behavioural symptoms of morphine withdrawal and prevents the depletion of spinal 
CGRP during withdrawal. To determine if morphine affects CGRP expression through a direct 
action on the primary afferent we have recently established an in vitro model of cultured adult 
dorsal root ganglion (DRG) neurons. Here we show that, similar to our in vivo studies, chronic 
morphine increases CGRP expression in DRG cultures and that this increase is completely 
blocked by CGRP8-37. These studies suggest that morphine acts on primary afferent neurons to 
augment CGRP expression which, in turn, contributes to the development of tolerance and 
physical dependence. In addition, these data show that CGRP mediates its own expression through 
activity of presynaptic CGRP receptors. Blockade of CGRP activity may have the potential to 
inhibit clinical opioid tolerance and physical dependence. [Supported by the Canadian Institutes of 
Health Research.] 
 
Submit your manuscripts at
http://www.hindawi.com
Pain
Research and Treatment
Hindawi Publishing Corporation
http://www.hindawi.com Volume 2014
The Scientific 
World Journal
Hindawi Publishing Corporation 
http://www.hindawi.com Volume 2014
Hindawi Publishing Corporation
http://www.hindawi.com
Volume 2014
Toxins
Journal of
Vaccines
Journal of
Hindawi Publishing Corporation 
http://www.hindawi.com Volume 2014
Hindawi Publishing Corporation
http://www.hindawi.com Volume 2014
Antibiotics
International Journal of
Toxicology
Journal of
Hindawi Publishing Corporation
http://www.hindawi.com Volume 2014
Stroke
Research and Treatment
Hindawi Publishing Corporation
http://www.hindawi.com Volume 2014
Drug Delivery
Journal of
Hindawi Publishing Corporation
http://www.hindawi.com Volume 2014
Hindawi Publishing Corporation
http://www.hindawi.com Volume 2014
Advances in 
Pharmacological 
Sciences
Tropical Medicine
Journal of
Hindawi Publishing Corporation
http://www.hindawi.com Volume 2014
Medicinal Chemistry
International Journal of
Hindawi Publishing Corporation
http://www.hindawi.com Volume 2014
Addiction
Journal of
Hindawi Publishing Corporation
http://www.hindawi.com Volume 2014
Hindawi Publishing Corporation
http://www.hindawi.com Volume 2014
BioMed 
Research International
Emergency Medicine 
International
Hindawi Publishing Corporation
http://www.hindawi.com Volume 2014
Hindawi Publishing Corporation
http://www.hindawi.com Volume 2014
 Autoimmune 
Diseases
Hindawi Publishing Corporation
http://www.hindawi.com Volume 2014
 Anesthesiology 
Research and Practice
Scientifica
Hindawi Publishing Corporation
http://www.hindawi.com Volume 2014
Journal of
Hindawi Publishing Corporation
http://www.hindawi.com Volume 2014
Pharmaceutics
Hindawi Publishing Corporation
http://www.hindawi.com Volume 2014
MEDIATORS
INFLAMMATION
of


The Role of CGRP in the Development of Morphine Tolerance and Physical Dependence

Directory of Open Access Journals

The Scientific World JOURNAL

http://doaj.org/search?source=%7B%22query%22%3A%7B%22bool%22%3A%7B%22must%22%3A%5B%7B%22term%22%3A%7B%22id%22%3A%225cd3f25aacfe4a9b85e13e27f528910f%22%7D%7D%5D%7D%7D%7D

The Role of CGRP in the Development of Morphine Tolerance and Physical Dependence

Abstract

Similar works

Full text

Available Versions

Crossref

Directory of Open Access Journals