| Indirect role of beta2-adrenergic receptors in the mechanism of analgesic action of nonsteroidal antiinflammatory drugs. | |
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MedLine Citation:
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PMID: 20601862 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVE: Adrenal gland hormones have been shown to have a role in the antiinflammatory effect mechanism of nonsteroidal antiinflammatory drugs. This study investigates whether the analgesic effects of indomethacin, diclofenac sodium, aspirin, and nimesulide (IDAN; upper case letters of the four drugs we used) are also related to adrenal gland hormones. DESIGN: The analgesic effects of IDAN were studied in the carrageenan-induced inflammatory pain model using both intact and adrenalectomized rats. Paw withdrawal tests were performed in adrenalectomized rats that had been pretreated with phenoxybenzamine, propranolol, and metoprolol. SETTING: This study was performed in Pharmacology and Biochemistry Laboratories of Faculty of Medicine. PATIENTS/SUBJECTS: A total of 306 (114 intact and 192 adrenalectomized) male Albino Wistar rats were used. INTERVENTIONS: Adrernalectomy, drug administrations, pain model induction and pain threshold measurements were performed during the study. MEASUREMENTS AND MAIN RESULTS: Although the analgesic effects of nonsteroidal antiinflammatory drugs were lost in adrenalectomized rats, they exerted significant analgesia in adrenalectomized rats that had been pretreated with prednisolone and adrenalin. All these drugs were found to decrease serum adrenalin concentration but did not change serum cortisole (corticosterone in rats) concentration. Prednisolone and adrenalin inhibited carrageenan-induced hyperalgesia in adrenalectomized rat groups pretreated with metoprolol or phenoxybenzamine, but not in rats given propranolol. Propranolol also negated the analgesic effects of IDAN in intact rats. The analgesic effects provided by either prednisolone or adrenalin could not be inhibited by the alpha1, alpha2, or beta1 blockers but disappeared when beta2 receptors were blocked. CONCLUSIONS: The analgesic effects of nonsteroidal antiinflammatory drugs appear to be related to endogenous adrenalin and cortisole. We have demonstrated that adrenalin and prednisolone play important roles in the analgesic effect mechanism of IDAN. Prednisolone and adrenalin produce analgesic effects through beta2-adrenergic receptors, suggesting an indirect role for beta2-adrenergic receptors in the analgesic effect mechanism of the nonsteroidal antiinflammatory drugs mentioned. |
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Authors:
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Elif Cadirci; Halis Suleyman; Ahmet Hacimuftuoglu; Zekai Halici; Fatih Akcay |
Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Critical care medicine Volume: 38 ISSN: 1530-0293 ISO Abbreviation: Crit. Care Med. Publication Date: 2010 Sep |
Date Detail:
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Created Date: 2010-08-20 Completed Date: 2010-09-27 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0355501 Medline TA: Crit Care Med Country: United States |
Other Details:
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Languages: eng Pagination: 1860-7 Citation Subset: AIM; IM |
Affiliation:
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Department of Pharmacology, Faculty of Pharmacy, Ataturk University, Erzurum, Turkey. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adrenalectomy Adrenergic alpha-Antagonists / administration & dosage Adrenergic beta-Antagonists / administration & dosage Analgesics / pharmacology*, therapeutic use Animals Anti-Inflammatory Agents, Non-Steroidal / pharmacology*, therapeutic use Male Metoprolol / administration & dosage Pain / drug therapy Phenoxybenzamine / administration & dosage Propranolol / administration & dosage Rats Rats, Wistar Receptors, Adrenergic, beta-2 / drug effects, physiology* |
| Chemical | |
Reg. No./Substance:
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0/Adrenergic alpha-Antagonists; 0/Adrenergic beta-Antagonists; 0/Analgesics; 0/Anti-Inflammatory Agents, Non-Steroidal; 0/Receptors, Adrenergic, beta-2; 37350-58-6/Metoprolol; 525-66-6/Propranolol; 59-96-1/Phenoxybenzamine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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