Formalin-induced pain and μ-opioid receptor density in brain and spinal cord are modulated by A1 and A2a adenosine agonists in mice

Borghi, Valentina; Przewłocka, Barbara; Łabuz, Dominika; Maj, Marcin; Obara, Ilona; Pavone, Flaminia

doi:10.1016/s0006-8993(02)03568-0

Cited by 28 publications

(12 citation statements)

References 30 publications

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“…On the other hand, Borghi et al demonstrated that the noxious stimulus increased the density of the μ receptors in the spinal cord and that the purinergic agonists reduced it in both the spinal cord and the PAG [44]. This evidence, together with the results of our study, suggests that caffeine, a nonselective antagonist of the purinergic receptors, when administered systemically, does not permit the reduction of the μ receptors, and therefore a greater density of these receptors can be activated by tramadol.…”

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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“…Moreover, it has been demonstrated that A 2A receptor antagonists showed consistent antinociceptive activity (Doak and Sawynok, 1995), and hypoalgesia in mice lacking the adenosine A 2A receptor was observed (Ledent et al, 1997). In the formalin test, CGS 21680 [3-[4-[2-[[6-amino-9-[(2R,3R,4S,5S)-5-(ethylcarbamoyl)-3,4-dihydroxy-oxolan-2-yl]purin-2-yl]amino] ethyl]phenyl]propanoic acid; agonist A 2A ] has been shown to produce both antinociceptive (Borghi et al, 2002) and pronociceptive actions in rats (Doak and Sawynok, 1995). However, some authors have shown that the activation of the adenosine A 2A receptor has an antinociceptive role against the chemical (writhing test) and thermal model of pain beyond inflammatory and neuropathic pain tests (Lee and Yaksh, 1996;Poon and Sawynok, 1998;Pechlivanova and Georgiev, 2002;Loram et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

Inosine Reduces Pain-Related Behavior in Mice: Involvement of Adenosine A₁ and A_2A Receptor Subtypes and Protein Kinase C Pathways

Nascimento

Figueredo²,

Marcon³

et al. 2010

J Pharmacol Exp Ther

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Inosine, an endogenous purine, is the first metabolite of adenosine in a reaction catalyzed by adenosine deaminase. This study aimed to investigate the antinociceptive effects of inosine against several models of pain in mice and rats. In mice, inosine given by systemic or central routes inhibited acetic acid-induced nociception. Furthermore, inosine also decreased the late phase of formalin-induced licking and the nociception induced by glutamate. Inosine produced inhibition (for up to 4 h) of mechanical allodynia induced by complete Freund's adjuvant (CFA) injected into the mouse's paw. Given chronically for 21 days, inosine reversed the mechanical allodynia caused by CFA. Moreover, inosine also reduced the thermal (cold stimuli) and mechanical allodynia caused by partial sciatic nerve ligation (PSNL) for 4 h; when inosine was chronically administered, it decreased the mechanical allodynia induced by PSNL for 22 days. Antinociception caused by inosine in the acetic acid test was attenuated by treatment of . In rats, inosine inhibited the mechanical and heat hyperalgesia induced by bradykinin and phorbol 12-myristate 13-acetate, without affecting similar responses caused by prostaglandin E 2 or forskolin. These results indicate that inosine induces antinociceptive, antiallodynic, and antihyperalgesic effects in rodents. The precise mechanisms through which inosine produces antinociception are currently under investigation, but involvement of adenosine A 1 and A 2A receptors and blockade of the protein kinase C pathway seem to largely account for inosine's antinociceptive effect.

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“…The aim of this study is to assess whether the use of intracoronary adenosine given directly into the coronary artery before stenting can reduce the incidence of myocardial necrosis and achieve better outcomes at 30-day follow-up. A similar study is under way at the University Hospital, Gasthuisberg, (Borghi et al, 2002;Hussey et al, 2007) or secondary to inhibiting inflammation as a consequence of A 2A R activation. The purpose of this study is to compare the effects of intrathecal clonidine and adenosine on neuropathic thermal pain.…”

Section: A Adenosinementioning

confidence: 97%

International Union of Basic and Clinical Pharmacology. LXXXI. Nomenclature and Classification of Adenosine Receptors—An Update

Fredholm¹,

IJzerman²,

Jacobson³

et al. 2011

Pharmacol Rev

1,925

2,797

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Formalin-induced pain and μ-opioid receptor density in brain and spinal cord are modulated by A1 and A2a adenosine agonists in mice

Cited by 28 publications

References 30 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

Inosine Reduces Pain-Related Behavior in Mice: Involvement of Adenosine A₁ and A_2A Receptor Subtypes and Protein Kinase C Pathways

International Union of Basic and Clinical Pharmacology. LXXXI. Nomenclature and Classification of Adenosine Receptors—An Update

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Formalin-induced pain and μ-opioid receptor density in brain and spinal cord are modulated by A1 and A2a adenosine agonists in mice

Cited by 28 publications

References 30 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

Inosine Reduces Pain-Related Behavior in Mice: Involvement of Adenosine A1 and A2A Receptor Subtypes and Protein Kinase C Pathways

International Union of Basic and Clinical Pharmacology. LXXXI. Nomenclature and Classification of Adenosine Receptors—An Update

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Inosine Reduces Pain-Related Behavior in Mice: Involvement of Adenosine A₁ and A_2A Receptor Subtypes and Protein Kinase C Pathways