Antinociceptive Tolerance to NSAIDs in the Anterior Cingulate Cortex is Mediated Via Endogenous Opioid Mechanism

Overview

Journal BMC Pharmacol Toxicol

Publisher Biomed Central

Specialty Pharmacology

Date 2018 Jan 7

PMID 29304875

Citations 9

Authors

Nana Tsiklauri

Natia Pirkulashvili

Ivliane Nozadze

Marina Nebieridze

Gulnaz Gurtskaia

Elene Abzianidze

Merab G Tsagareli

Affiliations

Soon will be listed here.

Abstract

Background: In the past decade several studies have reported that in some brain areas, particularly, in the midbrain periaqueductal gray matter, rostral ventro-medial medulla, central nucleus of amygdala, nucleus raphe magnus, and dorsal hippocampus, microinjections of non-steroidal anti-inflammatory drugs (NSAIDs) induce antinociception with distinct development of tolerance. Given this evidence, in this study we investigated the development of tolerance to the analgesic effects of NSAIDs diclofenac, ketorolac and xefocam microinjected into the rostral part of anterior cingulate cortex (ACC) in rats.

Methods: Male Wistar experimental and control (saline) rats were implanted with a guide cannula in the ACC and tested for antinociception following microinjection of NSAIDs into the ACC in the tail-flick (TF) and hot plate (HP) tests. Repeated measures of analysis of variance with post-hoc Tukey-Kramer multiple comparison tests were used for statistical evaluations.

Results: Treatment with each NSAID significantly enhanced the TF and HP latencies on the first day, followed by a progressive decrease in the analgesic effect over a 4-day period, i.e., developed tolerance. Pretreatment with an opioid antagonist naloxone completely prevented the analgesic effects of the three NSAIDs in both behavioral assays.

Conclusions: These findings support the concept that the development of tolerance to the antinociceptive effects of NSAIDs is mediated via an endogenous opioid system possibly involving descending pain modulatory systems.

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References

McKenna J, Melzack R . Analgesia produced by lidocaine microinjection into the dentate gyrus. Pain. 1992; 49(1):105-112. DOI: 10.1016/0304-3959(92)90195-H. View

Johansen J, Fields H, Manning B . The affective component of pain in rodents: direct evidence for a contribution of the anterior cingulate cortex. Proc Natl Acad Sci U S A. 2001; 98(14):8077-82. PMC: 35470. DOI: 10.1073/pnas.141218998. View

Tortorici V, Nogueira L, Salas R, Vanegas H . Involvement of local cholecystokinin in the tolerance induced by morphine microinjections into the periaqueductal gray of rats. Pain. 2003; 102(1-2):9-16. DOI: 10.1016/s0304-3959(02)00153-7. View

Pernia-Andrade A, Tortorici V, Vanegas H . Induction of opioid tolerance by lysine-acetylsalicylate in rats. Pain. 2004; 111(1-2):191-200. DOI: 10.1016/j.pain.2004.06.006. View

Tortorici V, Vanegas H . Opioid tolerance induced by metamizol (dipyrone) microinjections into the periaqueductal grey of rats. Eur J Neurosci. 2000; 12(11):4074-80. DOI: 10.1046/j.1460-9568.2000.00295.x. View

Tsagareli M, Nozadze I, Tsiklauri N, Gurtskaia G . Tolerance to Non-Opioid Analgesics is Opioid Sensitive in the Nucleus Raphe Magnus. Front Neurosci. 2011; 5:92. PMC: 3145141. DOI: 10.3389/fnins.2011.00092. View

Telleria-Diaz A, Schmidt M, Kreusch S, Neubert A, Schache F, Vazquez E . Spinal antinociceptive effects of cyclooxygenase inhibition during inflammation: Involvement of prostaglandins and endocannabinoids. Pain. 2009; 148(1):26-35. DOI: 10.1016/j.pain.2009.08.013. View

Tsagareli M, Tsiklauri N, Nozadze I, Gurtskaia G . Tolerance effects of non-steroidal anti-inflammatory drugs microinjected into central amygdala, periaqueductal grey, and nucleus raphe: Possible cellular mechanism. Neural Regen Res. 2015; 7(13):1029-39. PMC: 4341275. DOI: 10.3969/j.issn.1673-5374.2012.13.010. View

Ito T, Tanaka-Mizuno S, Iwashita N, Tooyama I, Shiino A, Miura K . Proton magnetic resonance spectroscopy assessment of metabolite status of the anterior cingulate cortex in chronic pain patients and healthy controls. J Pain Res. 2017; 10:287-293. PMC: 5293371. DOI: 10.2147/JPR.S123403. View

10.

Vazquez E, Escobar W, Ramirez K, Vanegas H . A nonopioid analgesic acts upon the PAG-RVM axis to reverse inflammatory hyperalgesia. Eur J Neurosci. 2007; 25(2):471-9. DOI: 10.1111/j.1460-9568.2007.05280.x. View

11.

Tasker R, Choiniere M, Libman S, Melzack R . Analgesia produced by injection of lidocaine into the lateral hypothalamus. Pain. 1987; 31(2):237-248. DOI: 10.1016/0304-3959(87)90039-X. View

12.

Hernandez-Delgadillo G, Cruz S . Endogenous opioids are involved in morphine and dipyrone analgesic potentiation in the tail flick test in rats. Eur J Pharmacol. 2006; 546(1-3):54-9. DOI: 10.1016/j.ejphar.2006.07.027. View

13.

Vanegas H, Vazquez E, Tortorici V . NSAIDs, Opioids, Cannabinoids and the Control of Pain by the Central Nervous System. Pharmaceuticals (Basel). 2016; 3(5):1335-1347. PMC: 4033984. DOI: 10.3390/ph3051335. View

14.

Tortorici V, Aponte Y, Acevedo H, Nogueira L, Vanegas H . Tolerance to non-opioid analgesics in PAG involves unresponsiveness of medullary pain-modulating neurons in male rats. Eur J Neurosci. 2009; 29(6):1188-96. DOI: 10.1111/j.1460-9568.2009.06678.x. View

15.

Casey K . Concepts of pain mechanisms: the contribution of functional imaging of the human brain. Prog Brain Res. 2000; 129:277-87. DOI: 10.1016/S0079-6123(00)29020-1. View

16.

Tsiklauri N, Viatchenko-Karpinski V, Voitenko N, Tsagareli M . Non-opioid tolerance in juvenile and adult rats. Eur J Pharmacol. 2009; 629(1-3):68-72. DOI: 10.1016/j.ejphar.2009.12.016. View

17.

Gurtskaia G, Tsiklauri N, Nozadze I, Nebieridze M, Tsagareli M . Antinociceptive tolerance to NSAIDs microinjected into dorsal hippocampus. BMC Pharmacol Toxicol. 2014; 15:10. PMC: 3945813. DOI: 10.1186/2050-6511-15-10. View

18.

Vaccarino A, Melzack R . Analgesia produced by injection of lidocaine into the anterior cingulum bundle of the rat. Pain. 1989; 39(2):213-219. DOI: 10.1016/0304-3959(89)90008-0. View

19.

Vanegas H, Tortorici V . Opioidergic effects of nonopioid analgesics on the central nervous system. Cell Mol Neurobiol. 2003; 22(5-6):655-61. PMC: 11533735. DOI: 10.1023/a:1021896622089. View

20.

Tsiklauri N, Nozadze I, Gurtskaia G, Tsagareli M . Antinociceptive tolerance to NSAIDs in the rat formalin test is mediated by the opioid mechanism. Pharmacol Rep. 2016; 69(1):168-175. DOI: 10.1016/j.pharep.2016.10.004. View