|ognizant Communication Corporation|
REVIEWS IN ANALGESIA
VOLUME 8, NUMBER 1
Reviews in Analgesia, Vol. 8, pp. 1-10
1542-961X/04 $20.00 + .00
Copyright © 2004 Cognizant Comm. Corp.
Printed in the USA. All rights reserved.
Pain, the Immune System, and Opioimmunotoxicity
Emeritus Consultant in Pain Management, Ilkley LS29 6PE, UK
In humans, the trauma of surgery and the pain it produces suppress the immune system for varying lengths of time. As the pain and trauma contribute independently to the immunosuppression, the administration of analgesic and anti-inflammatory agents should prevent this happening. Unfortunately, for the last five decades, evidence has been accruing that the majority of strong opioid analgesics produce significant immunosuppression at doses within the antinociceptive range. This opioid-induced suppression has been shown to lead to increased susceptibility to both bacterial and viral infection, reduced tolerance to cancer with increased metastatic spread, and greater susceptibility to HIV infections in drug abusers. However, there is a small number of opioid analgesics having no immunotoxic effects and these can be readily delineated by their characteristic molecular configuration and, consequently, should be used in preference to the immunosuppressive variety.
Key words: Pain; Immune system; Opioid analgesic; Immunosuppression; Molecular structure/function relationship
Address correspondence to Dr. Keith Budd, Emeritus Consultant in Pain Management, "Newlands," Chevin Avenue, The Homestead, Menston, Ilkley LS29 6PE, UK. Tel: 00 44 (0)1943 876331; Fax: 00 44 (0)1943 870456; E-mail: firstname.lastname@example.org
G-Protein Coupling and Efficacy of Mu-Opioid Agonists: Relationship to Behavioral Efficacy
J. R. Traynor
Department of Pharmacology, University of Michigan Medical School, Ann Arbor, MI
Efficacy describes the ability of a drug to produce a response. The efficacy of mu-opioid agonists is an important consideration in their behavioral and clinical profile and can be measured at any functional endpoint between receptor occupancy and the resulting behavior. Measures of efficacy are dependent upon both the intrinsic efficacy specific to the drug and tissue parameters, in particular receptor number. This article considers measures of efficacy at both the earliest measurable event following mu-opioid receptor occupation by an agonist, namely the activation of G proteins as measured by the binding of [35S]GTPgS, and the final event, the observed behavior. Many mu-opioids show potency differences but often the maximal effect is the same. However, drugs can be separated in both G protein activity and behavioral assays by increasing the stringency of the assay or by reduction in the efficiency of the system following tolerance development or reduction in receptor number using irreversible antagonists. The order of efficacy is the same at the very separate stages of drug effect from receptor activation to behavioral endpoint, confirming the strength of the concept of intrinsic efficacy.
Key words: Mu-opioids; Efficacy; Potency; G protein; Behavior
Address correspondence to J. R. Traynor, Department of Pharmacology, University of Michigan Medical School, 1301 MSRBIII, West Medical Center Drive, Ann Arbor, MI 48109-0632. Tel: (734) 647-7479; Fax: (734) 763-4450; E-mail: email@example.com
What Is Different About Pain in Older Persons?
Stephen J. Gibson1,2,3 and Michael Farrell1,4
1National Ageing Research Institute, Parkville, VIC, Australia
2Department of Medicine, University of Melbourne, VIC, Australia 3052
3Caulfield Pain Management and Research Centre, Caulfield, VIC, Australia 3162
4Howard Florey Institute, Parkville, VIC, Australia 3050
Despite the massive demographic shift in age composition of the world's population, there has been relatively little study of how age might impact on the pain experience. An age-related increase in the prevalence of persistent pain has been well documented, but most studies of clinical disease document a significant reduction in the frequency and intensity of pain symptoms with advancing age. Evidence from studies of experimental pain suggests a differential age effect across the pain intensity spectrum, with a diminished response to mild pain and greater vulnerability to strong pain sensations. There are many reasons for altered pain perception and report in older adults, including age differences in the nociceptive pathways, psychological factors such as greater stoicism and the contribution of more indirect influences, like increased comorbid disease and loss of social support networks. The aging population will place an increased demand on existing pain services and require new and innovative evidence-based treatment guidelines in order to meet the special needs of older persons with bothersome pain. Additional research efforts are needed to meet this important challenge and improve treatment strategies for managing the widespread pain and suffering in the older segments of our community.
Key words: Pain perception; Age-related differences; Treatment strategies
Address correspondence to Stephen Gibson, Associate Professor, National
Ageing Research Institute, PO Box 31, Parkville, VIC Australia 3052. E-mail: