Ondansetron Inhibits the Analgesic Effects of Tramadol: A Possible 5-HT3 Spinal Receptor Involvement in Acute Pain in Humans

Arcioni, R.; Rocca, Marco della; Romanò, Sarah; Romano, Rocco; Pietropaoli, P; Gasparetto, A

doi:10.1097/00000539-200206000-00033

Cited by 61 publications

(22 citation statements)

References 16 publications

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“…The role that 5-HT 3 receptors play in regard to pain is controversial. Reports have stated that these receptors are not involved in the thermal pain inhibition produced by tramadol [20], whereas it was observed that in humans ondansetron inhibited tramadol's analgesic effect in postoperative pain [38]. On the other hand, Dogrul et al report that the spinal 5-HT 3 receptor participates in the antiallodynic and antihyperalgesic effect of tramadol, whereas the 5-HT 7 receptors participate in the antinociceptive effect [19].…”

Section: Discussionmentioning

confidence: 99%

Tramadol and Tramadol+Caffeine Synergism in the Rat Formalin Test Are Mediated by Central Opioid and Serotonergic Mechanisms

Carrillo-Munguía

González-Trujano

Huerta

et al. 2015

BioMed Research International

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Different analgesic combinations with caffeine have shown this drug to be capable of increasing the analgesic effect. Many combinations with nonsteroidal anti-inflammatory drugs (NSAIDs) have been carried out, but, in regard to opioids, only combinations with morphine and tramadol have been reported. The antinociceptive synergism mechanism of these combinations is not well understood. The purpose of the present study was to determine the participation of spinal and supraspinal opioidergic and serotonergic systems in the synergic effect of the tramadol+caffeine combination in the rat formalin test. At the supraspinal level, the opioid antagonist, naloxone, completely reversed the effect of the drug combination, whereas ketanserin, a 5-HT2 receptor antagonist, inhibited the effect by 60%; however, ondansetron, a 5-HT3 receptor antagonist, did not alter the combination effect. When the antagonists were intrathecally administered, there was a significant reduction in all tramadol-caffeine combination effects. With respect to tramadol alone, there was significant participation of the opioid system at the supraspinal level, whereas it was the serotonergic system that participated at the spinal level by means of the two receptors studied. In conclusion, the tramadol+caffeine combination synergically activated the opioid and serotonergic systems at the supraspinal level, as well as at the spinal level, to produce the antinociception.

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Section: Discussionmentioning

confidence: 99%

Tramadol and Tramadol+Caffeine Synergism in the Rat Formalin Test Are Mediated by Central Opioid and Serotonergic Mechanisms

Carrillo-Munguía

González-Trujano

Huerta

et al. 2015

BioMed Research International

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“…Also, the antinociceptive effect of tramadol was significantly diminished in 5-HT-lesioned mice. Previous data suggested that the descending serotonergic pathways and spinal 5-HT receptors play a crucial role in the antinociceptive and antihyperalgesic effects of tramadol [38,39]. On the other hand, another recent study observed that the intrathecal injection of minocycline significantly attenuated mechanical allodynia in a rat SNL model [40].…”

Section: Discussionmentioning

confidence: 99%

Depressing Interleukin-1� Contributed to the Synergistic Effects of Tramadol and Minocycline on Spinal Nerve Ligation-Induced Neuropathic Pain

Mei

Sakuma²,

Xie

et al. 2014

Neurosignals

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Our previous study indicated that coadministration of tramadol and minocycline exerted synergistic effects on spinal nerve ligation (SNL)-induced neuropathic mechanical allodynia. However, the underlying mechanisms are still unclear. Recent reports indicated that spinal proinflammatory factor interleukin-1β (IL-1β) contributed to the development of neuropathic pain and the positive feedback communication between neuron and glia. Therefore, the present research is to confirm whether spinal IL-1β-related pathway response contributes to the synergistic effects of tramadol and minocycline on SNL-induced neuropathic pain. Real-time RT-PCR demonstrated IL-1β up-expression in the ipsilateral spinal dorsal horn 3 days after lesion, which could be significantly decreased by tramadol and minocycline coadministration. Immunofluorescence and Western blot indicated that SNL-induced microglial phosphorylated p38 (p-p38) upregulation was also inhibited by tramadol and minocycline coapplication. Meanwhile, intrathecal administration of p38 inhibitor SB203580 markedly alleviated mechanical allodynia whilst reducing IL-1β and Fos expression induced by SNL. Moreover, intrathecal neutralized antibody of IL-1β could depress SNL-induced mechanical allodynia and Fos expression. These results suggest that depressing SNL-induced aberrant activation of the spinal dorsal horn IL-1β-related pathway contributes to the underlying mechanism of the synergistic effects of tramadol and minocycline coadministration on SNL-induced neuropathic mechanical allodynia. © 2013 S. Karger AG, Basel

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“…Ondansetron, a serotonin 5-HT3 receptor antagonist, α7 nAChR antagonist and antiemetic, produced significant decreases in alcohol consumption in early onset alcohol-dependent individuals compared to late-onset alcoholics in an open-label 8-week study (Arcioni et al, 2002; Kranzler et al, 2003). These findings were consistent with others who found that ondansetron dose-dependently promoted abstinence in early-onset patients, but not in late-onset patients (Roache et al, 2008).…”

Section: Need: a Better Understanding Of The Co-morbid Conditionmentioning

confidence: 99%

Critical needs in drug discovery for cessation of alcohol and nicotine polysubstance abuse

Skike

Maggio

Reynolds

et al. 2016

Progress in Neuro-Psychopharmacology and Biological Psychiatry

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Polysubstance abuse of alcohol and nicotine has been overlooked in our understanding of the neurobiology of addiction and especially in the development of novel therapeutics for its treatment. Estimates show that as many as 92% of people with alcohol use disorders also smoke tobacco. The health risks associated with both excessive alcohol consumption and tobacco smoking create an urgent biomedical need for the discovery of effective cessation treatments, as opposed to current approaches that attempt to independently treat each abused agent. The lack of treatment approaches for alcohol and nicotine abuse/dependence mirrors a similar lack of research in the neurobiology of polysubstance abuse. This review discusses three critical needs in medications development for alcohol and nicotine co-abuse: (1) the need for a better understanding of the clinical condition (i.e. alcohol and nicotine polysubstance abuse) (2) the need to better understand how these drugs interact in order to identify new targets for therapeutic development and (3) the need for animal models that better mimic this human condition. Current and emerging treatments available for the cessation of each drug and their mechanisms of action are discussed within this context followed by what is known about the pharmacological interactions of alcohol and nicotine. Much has been and will continue to be gained from studying comorbid alcohol and nicotine exposure.

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Ondansetron Inhibits the Analgesic Effects of Tramadol: A Possible 5-HT3 Spinal Receptor Involvement in Acute Pain in Humans

Cited by 61 publications

References 16 publications

Tramadol and Tramadol+Caffeine Synergism in the Rat Formalin Test Are Mediated by Central Opioid and Serotonergic Mechanisms

Tramadol and Tramadol+Caffeine Synergism in the Rat Formalin Test Are Mediated by Central Opioid and Serotonergic Mechanisms

Depressing Interleukin-1� Contributed to the Synergistic Effects of Tramadol and Minocycline on Spinal Nerve Ligation-Induced Neuropathic Pain

Critical needs in drug discovery for cessation of alcohol and nicotine polysubstance abuse

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