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REVIEWS IN ANALGESIA
An International Journal
VOLUME 8, NUMBER 2
Reviews in Analgesia, Vol. 8, pp. 57-69
1542-961X/05 $20.00 + .00
Copyright © 2004 Cognizant Comm. Corp.
Printed in the USA. All rights reserved.
The AMPA Receptor in Descending Circuitry: Role in Activity-Dependent Plasticity
Cynthia L. Renn,1 Yun Guan,1 Wei Guo,2 Ronald Dubner,2 and Ke Ren2
1Department of Organizational Systems & Adult Health,
School of Nursing, University of Maryland, Baltimore, MD 21201, USA
2Department of Biomedical Sciences, Dental School, and Program in Neuroscience, University of Maryland, Baltimore, MD 21201, USA
Neurons throughout the rostral ventromedial medulla (RVM), a pivotal structure in descending pain modulatory circuitry, express the a-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) subtype of glutamate receptors. Recent studies suggest that glutamatergic neurotransmission, through AMPA receptors, plays a key role in the development of activity-dependent plasticity in the RVM in response to persistent inflammatory hyperalgesia. Peripheral inflammation induces a time-dependent enhancement of AMPA-produced descending inhibition, an upregulation of AMPA receptor GluR1 subunit expression associated with an increased neuronal activation in the RVM, and an increase in the level of GluR1 phosphorylation. These convergent findings suggest that neuronal activation and GluR1 expression/activation contribute to the enhanced descending pain modulation after inflammatory hyperalgesia. The increased AMPA neurotransmission in the RVM, together with an increase in N-methyl-D-aspartate receptor activation, leads to increased excitability and activity-dependent plasticity in the brain stem pain modulatory circuitry.
Key words: Descending modulation; AMPA; GluR1; Phosphoserine 831 GluR1; Inflammation; Hyperalgesia; Rostral ventromedial medulla
Address correspondence to Ke Ren, Ph.D., Department of Biomedical Sciences, Room 5A12, Dental School, University of Maryland, 666 West Baltimore Street, Baltimore, MD 21201-1586, USA. Tel: (410) 706-3250; Fax: (410) 706-4172; E-mail: email@example.com
Analgesic Patent Applications: I
Robert B. Raffa
Temple University School of Pharmacy, Philadelphia, PA, USA
The United States Patent and Trademark Office webpage was searched for recent applications related to analgesia. The search identified 475 applications filed since March 15, 2001 containing the word "pain" in the title. In this first part of a multipart series examining trends in analgesic research and application, the list is presented. Future articles in the series will present individual applications.
Key words: Patent; Pain treatment; Pain relief; Analgesia
Address correspondence to Robert B. Raffa, Ph.D., Temple University School of Pharmacy, 3307 N. Broad Street, Philadelphia, PA 19140, USA. Tel: (215) 707-4976; Fax: (215) 707-5228; E-mail: firstname.lastname@example.org
Trigeminal Central Sensitization
Barry J. Sessle
Faculty of Dentistry and Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, Canada
Several orofacial pain conditions can present diagnostic and management challenges to the clinician. This is especially the situation for chronic pain cases because the etiology and pathogenesis are unknown or at least not well understood for most of these chronic conditions. However, recent research in animals and humans has revealed a mechanism in the central nervous system that may represent a common thread in the development and maintenance of many of these pain conditions. This mechanism has been termed "central sensitization" and will be the focus of this review article within the framework of the trigeminal system. The article first provides an organizational and conceptual framework for the reader by giving an overview of current knowledge of the trigeminal nociceptive pathways and their organization and neuronal features. Next, an outline is provided of findings bearing on the expression of central sensitization in the trigeminal system. The article concludes by pointing out some of the clinical implications of the findings.
Key words: Orofacial pain; Chronic pain; Central sensitization; Trigeminal nociceptive pathways
Address correspondence to Dr. Barry J. Sessle, Faculty of Dentistry, University of Toronto, 124 Edward Street, Toronto, Ontario, Canada M5G 1G6. Tel: 1-416-979-4921, Ext. 4336; Fax: 1-416-979-4936; E-mail: email@example.com
Peripheral Cannabinoid Analgesia: Neuronal and Immune Mechanisms
W. Paul Farquhar-Smith
Royal Marsden Hospital, Fulham Road, London, UK
There is a wealth of animal data demonstrating cannabinoids to be analgesic. However, the well-known psychoactive central side effects resulting from cannabinoid action on neuronal cannabinoid CB1 receptors in the brain have limited the human use of cannabinoids in pain management. Exploitation of peripheral mechanisms potentially allows dissociation between analgesia and the unwanted cannabinoid "high." This could involve singling out actions of peripheral neuronal cannabinoid receptors or utilization of receptors outwith the central nervous system, such as the cannabinoid CB2 receptor, expressed predominantly on immune cells. Multiple lines of evidence report peripheral analgesia via both CB1 and CB2 receptors. Neuronal actions and alteration of immune processes involved in the development of pain states are implicated. Therefore, development of cannabinoid analgesics directed at these peripheral targets offer a feasible therapeutic strategy devoid of central side effects.
Key words: Endocannabinoids; Mast cell; Neutrophils; Immunomodulation
Address correspondence to W. Paul Farquhar-Smith, Royal Marsden Hospital, Fulham Road, London, SW3 6JJ UK. Tel: 0207 808 2727; Fax: 020 7352 9756; E-mail: firstname.lastname@example.org