NSAIDs, Opioids, Cannabinoids and the Control of Pain by the Central Nervous System

Vanegas, Horacio; Vázquez, Enrique; Tortorici, Vı́ctor

doi:10.3390/ph3051335

Cited by 46 publications

(51 citation statements)

References 81 publications

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“…These findings strongly support the suggestion of endogenous opioid involvement in NSAIDs antinociception and tolerance in the descending pain-control system [15-19]. However, involvement of NSAIDs antinociception in the HF is still a matter of controversy.…”

Section: Introductionsupporting

confidence: 87%

“…When tolerance develops, PAG microinjections of morphine [32], or metamizol [15], are no longer capable of affecting RVM neurons and inducing analgesia. These results show further neuronal relationships between opioid and non-opioid analgesics as regards the descending pain-control and modulation system [19,30]. In addition, metamizol probably can act via endocannabinoids in the downstream PAG-RVM axis reducing inflammation pain in rats [33].…”

Section: Discussionmentioning

confidence: 79%

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Antinociceptive tolerance to NSAIDs microinjected into dorsal hippocampus

Gurtskaia¹,

Tsiklauri²,

Nozadze³

et al. 2014

BMC Pharmacol Toxicol

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BackgroundPain is characterized as a complex experience, dependent not only on the regulation of nociceptive sensory systems, but also on the activation of mechanisms that control emotional processes in limbic brain areas such as the amygdala and the hippocampus. Several lines of investigations have shown that in some brain areas, particularly the midbrain periaqueductal gray matter, rostral ventro-medial medulla, central nucleus of amygdala and nucleus raphe magnus, microinjections of non-steroidal anti-inflammatory drugs (NSAIDs) induce antinociception with distinct development of tolerance. The present study was designed to examine whether microinjection of NSAIDs, clodifen, ketorolac and xefocam into the dorsal hippocampus (DH) leads to the development of antinociceptive tolerance in male rats.MethodsThe experiments were carried out on experimental and control (with saline) white male rats. Animals were implanted with a guide cannula in the DH and tested for antinociception following microinjection of NSAIDs into the DH 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.ResultsWe found that microinjection of these NSAIDs into the DH induces antinociception as revealed by a latency increase in the TF and HP tests compared to controls treated with saline into the DH. Subsequent tests on days 2 and 3, however, showed that the antinociceptive effect of NSAIDs progressively decreased, suggesting tolerance developed to this effect of NSAIDs. Both pretreatment and post-treatment with the opioid antagonist naloxone into the DH significantly reduced the antinociceptive effect of NSAIDs in both pain models.ConclusionsOur results indicate that microinjection of NSAIDs into the DH induces antinociception which is mediated via the opioid system and exhibits tolerance.

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Section: Introductionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 79%

Antinociceptive tolerance to NSAIDs microinjected into dorsal hippocampus

Gurtskaia¹,

Tsiklauri²,

Nozadze³

et al. 2014

BMC Pharmacol Toxicol

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show abstract

“…We have also revealed that repeated microinjections of these nonopioids into the dorsal hippocampus (DH), the nucleus raphe magnus (NRM), and the central nucleus of amygdala (CeA) induce antinociception and the effects of tolerance and cross-tolerance to morphine 8,9,13–15. These findings strongly support the suggestion of endogenous opioids involvement in NSAIDs antinociception and tolerance in the descending pain-control system 8,16…”

Section: Introductionsupporting

confidence: 75%

“…According to the recently established concept, the mechanism producing tolerance to NSAIDs can be due to involvement of endogenous opioid peptides 8,16,23,24. In this study, we have clearly shown that pre- and posttreatment of a nonselective opioid receptor antagonist naloxone significantly diminishes NSAIDs-induced antinociception.…”

Section: Discussionmentioning

confidence: 99%

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Antinociceptive tolerance to NSAIDs in the agranular insular cortex is mediated by opioid mechanism

Pirkulashvili¹,

Tsiklauri²,

Nebieridze³

et al. 2017

JPR

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Several lines of investigations have shown that in some brain areas, in particular, in the midbrain periaqueductal gray matter, rostral ventromedial medulla, central nucleus of amygdala, nucleus raphe magnus, and dorsal hippocampus, microinjections of nonsteroidal anti-inflammatory drugs (NSAIDs) induce antinociception with distinct development of tolerance. The agranular insular cortex (AIC) is a small region of the cerebral cortex located on the lateral area of the rat’s cerebral hemisphere that is involved in the perception and response to pain. In the present study, we investigated the development of tolerance to the analgesic effects of NSAIDs diclofenac, ketorolac, and xefocam microinjected into the AIC in rats. Male Wistar rats receiving NSAIDs into the AIC were tested for antinociception by tail-flick and hot plate tests. Treatment with each NSAID significantly enhanced the tail-flick and hot plate latencies on the first day, followed by a progressive decrease in the analgesic effect over a 4-day period, ie, they developed tolerance. Pretreatment with an opioid antagonist naloxone completely prevented, and posttreatment naloxone abolished, the analgesic effects of the three NSAIDs in both behavioral assays. These findings support the notion 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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Antiallodynic Activity of Ceftriaxone and Clavulanic Acid in Acute Administration is Associated with Serum TNF‐α Modulation and Activation of Dopaminergic and Opioidergic Systems

Ochoa-Aguilar

Sotomayor-Sobrino

Jaimez

et al. 2017

Drug Development Research

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Preclinical Research The aim of this study was to determine the antiallodynic effect of acute administration of the β-lactam antimicrobials, ceftriaxone (CFX) and clavulanic acid (CLAV), for the control of established pain on a model of neuropathic pain (NP). We also investigated the involvement of dopaminergic and opioidergic pathways as well as alterations in serum concentrations of TNF-α in the antiallodynic actions of these drugs. CFX, CLAV, or gabapentin (GAP), a reference drug, were administered i.p. twelve days after constriction of the sciatic nerve in rats. Mechanic and cold allodynia were evaluated for 3 h and alterations in serum concentration of TNF-α determined. Both CFX and CLAV had antiallodynic effects in response to mechanical and cold stimulation, similar to GAP. The antiallodynic effects of CFX and CLAV were blocked by haloperidol (HAL), a D2 receptor antagonist, and by naloxone (NLX), an opioid receptor antagonist. Additionally, serum TNF-α levels were attenuated following CFX and CLAV administration. These results suggest that acute administration of CFX and CLAV may represent a promising approach for treating the acute allodynia of NP, and that the mechanisms involved in these effects involve activation of dopaminergic and opioidergic pathways as well as modulation of TNF-α production. Drug Dev Res 78 : 105-115, 2017. © 2017 Wiley Periodicals, Inc.

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NSAIDs, Opioids, Cannabinoids and the Control of Pain by the Central Nervous System

Cited by 46 publications

References 81 publications

Antinociceptive tolerance to NSAIDs microinjected into dorsal hippocampus

Antinociceptive tolerance to NSAIDs microinjected into dorsal hippocampus

Antinociceptive tolerance to NSAIDs in the agranular insular cortex is mediated by opioid mechanism

Antiallodynic Activity of Ceftriaxone and Clavulanic Acid in Acute Administration is Associated with Serum TNF‐α Modulation and Activation of Dopaminergic and Opioidergic Systems

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