Involvement of nitridergic and opioidergic pathways in the antinociception of gabapentin in the orofacial formalin test in mice

Miranda, Hugo F.; Sierralta, Fernando; Lux, Sebastián; Troncoso, Rocï¿1⁄2o; Ciudad, Natalia; Zepeda, Ramiro; Zanetta, Pilar; Noriega, Viviana; Prieto, Juan Carlos

doi:10.1016/j.pharep.2014.10.018

Cited by 11 publications

(6 citation statements)

References 24 publications

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“…18 Another study also showed an effect of naltrexone on the acute action of gabapentin in a model of orofacial inflammatory pain. 19 These recent data differ from previous studies on gabapentinoid drugs, which mostly reported naloxone to be ineffective in blocking gabapentinoid-induced analgesia in different pain models. [20][21][22] However, most of these studies were not done in models of neuropathic pain, which is the clinical pain condition for which gabapentinoids have legal authorization for prescription in various countries.…”

Section: Acute Salinecontrasting

confidence: 70%

“…In addition to these actions, two studies suggested that gabapentinoids may also recruit the endogenous opioid system, 18,19 which is well known for playing a crucial role in the control of nociception and pain. 10,11,52 Indeed, the opioid antagonist naloxone reversed the acute antinociceptive activity of a high dose of pregabalin in naive mice.…”

Section: Discussionmentioning

confidence: 99%

“…A potential role of the opioid system has been recently suggested in the central, acute, analgesic effect of a high dose of pregabalin in the tail flick test in naive mice, 18 and in the antinociceptive response induced by acute gabapentin in a model of acute inflammatory pain, the orofacial formalin test in mice. 19 On the contrary, previous pharmacological studies reported no effect of opioid antagonists on gabapentinoid action. [20][21][22] For example, naloxone do not block acute pregabalin action on abdominal constrictions in the lipopolysaccharide (LPS)-induced rectal hypersensitivity model of visceral pain; 21 and naloxone do not block acute gabapentin action in the formalin test, a model of inflammatory pain.…”

Section: Introductionmentioning

confidence: 95%

“…Pregabalin antiallodynic effect is associated with decreased trafficking of the a2d-1 subunit to presynaptic terminals of DRG neurons; 8,46 and within the dorsal horn, gabapentinoids also decrease the amplitude of excitatory postsynaptic currents. 51 In addition to these actions, two studies suggested that gabapentinoids may also recruit the endogenous opioid system, 18,19 which is well known for playing a crucial role in the control of nociception and pain. 10,11,52 Indeed, the opioid antagonist naloxone reversed the acute antinociceptive activity of a high dose of pregabalin in naive mice.…”

Section: Acute Salinementioning

confidence: 99%

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The antiallodynic action of pregabalin in neuropathic pain is independent from the opioid system

et al. 2016

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BackgroundClinical management of neuropathic pain, which is pain arising as a consequence of a lesion or a disease affecting the somatosensory system, partly relies on the use of anticonvulsant drugs such as gabapentinoids. Therapeutic action of gabapentinoids such as gabapentin and pregabalin, which act by the inhibition of calcium currents through interaction with the α2δ-1 subunit of voltage-dependent calcium channels, is well documented. However, some aspects of the downstream mechanisms are still to be uncovered. Using behavioral, genetic, and pharmacological approaches, we tested whether opioid receptors are necessary for the antiallodynic action of acute and/or long-term pregabalin treatment in the specific context of neuropathic pain.ResultsUsing the cuff model of neuropathic pain in mice, we show that acute pregabalin administration at high dose has a transitory antiallodynic action, while prolonged oral pregabalin treatment leads to sustained antiallodynic action, consistent with clinical observations. We show that pregabalin remains fully effective in μ-opioid receptor, in δ-opioid receptor and in κ-opioid receptor deficient mice, either female or male, and its antiallodynic action is not affected by acute naloxone. Our work also shows that long-term pregabalin treatment suppresses tumor necrosis factor-α overproduction induced by sciatic nerve constriction in the lumbar dorsal root ganglia.ConclusionsWe demonstrate that neither acute nor long-term antiallodynic effect of pregabalin in a context of neuropathic pain is mediated by the endogenous opioid system, which differs from opioid treatment of pain and antidepressant treatment of neuropathic pain. Our data are also supportive of an impact of gabapentinoid treatment on the neuroimmune aspect of neuropathic pain.

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Section: Acute Salinecontrasting

confidence: 70%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 95%

Section: Acute Salinementioning

confidence: 99%

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The antiallodynic action of pregabalin in neuropathic pain is independent from the opioid system

et al. 2016

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“…In addition to the mechanisms described above, other targets could modulate antinociception induced by rosuvastatin, such as opioid receptors and other mediators. To study the involvement of MOR, DOR, and KOR in antinociception induced by rosuvastatin, naltrexone, naltrindole, and norbinaltorphimine have been used at doses that block MOR, DOR, and KOR, respectively [21,22]. It was reported early on that selective opioid receptor blockers induce analgesia in mice as well as in rats [23].…”

Section: Discussionmentioning

confidence: 99%

Antinociception induced by rosuvastatin in mice: Modulation by opioid receptor antagonists, risperidone and l-name

Juan Carlos Prieto,

Viviana Noriega,

Hugo F Miranda

2024

GSC Adv. Res. Rev.

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Statins are widely used in cardiovascular disease as cholesterol lowering drugs. However, they also have other actions (pleiotropic effects) including antiproliferative, antithrombotic, neuroprotective, immunomodulatory, anti-inflammatory and antinociceptive activity. The aim of this study was to determine the antinociception properties of rosuvastatin in two murine models of pain and the involvement of opioid antagonists (naltrexone, naltrindole, norbinaltorphimine), risperidone, and L-NAME (L-NG-nitro arginine methyl ester) in this effect. Rosuvastatin was chosen among available statins because it is commonly prescribed and has high potency, efficacy, and an acceptable safety profile. Rosuvastatin antinociception was evaluated in the acetic acid writhing test and the formalin hind paw test by dose-response curves, before and after the i.p. administration of opioid antagonists, risperidone, and L-NAME. This work demonstrates that the assayed drugs modulate the antinociceptive effect of rosuvastatin in both experimental murine pain tests. The antinociception effect described for rosuvastatin may be due to a particular modulation induced by the opioid antagonists, risperidone and L-NAME. Given the broad effects of rosuvastatin, the results of this study may have novel clinical implications in the therapy of pain.

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Involvement of NO/cGMP pathway in the antidepressant-like effect of gabapentin in mouse forced swimming test

Ostadhadi

Kordjazy

Haj‐Mirzaian

et al. 2016

Naunyn-Schmiedeberg's Arch Pharmacol

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Based on clinical studies regarding the beneficial effect of gabapentin in depression, we aimed to evaluate the antidepressant-like properties of gabapentin in mice and also the participation of nitric oxide (NO)/cyclic guanosine monophosphate pathway in this effect. The following drugs were used in this study: gabapentin; N(G)-nitro-L-arginine methyl ester (L-NAME), a non-specific NO synthase (NOS) inhibitor; 7-nitroindazole, a specific neuronal NOS inhibitor; aminoguanidine, a specific inducible NOS inhibitor; L-arginine, a NO precursor; and sildenafil, a phosphodiestrase inhibitor. Finally, we studied the behavioral effects through the forced swimming test (FST) and the changes of the hippocampus NO level through nitrite assay. The immobility time was significantly reduced after gabapentin administration. Co-administration of non-effective doses of gabapentin and L-NAME or 7-nitroindazole (7-NI) resulted in antidepressant-like effect in FST, while aminoguanidine did not affect the immobility time of gabapentin-treated mice. Furthermore, the antidepressant-like property of gabapentin was prevented by L-arginine or sildenafil. Also, the hippocampal nitrite level was significantly lower in gabapentin-treated mice relative to saline-injected mice, and co-administration of 7-NI with sub-effective gabapentin caused a significant decrease in hippocampal nitrite levels. Our results indicate that the antidepressant-like effect of gabapentin in the mice FST model is mediated at least in part through nitric oxide/cyclic guanosine monophosphate (cGMP) pathway.

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Involvement of nitridergic and opioidergic pathways in the antinociception of gabapentin in the orofacial formalin test in mice

Abstract: These results suggest that gabapentin produce antinociception partly via the activation nitridergic pathways and opioid system.

Cited by 11 publications

References 24 publications

The antiallodynic action of pregabalin in neuropathic pain is independent from the opioid system

The antiallodynic action of pregabalin in neuropathic pain is independent from the opioid system

Antinociception induced by rosuvastatin in mice: Modulation by opioid receptor antagonists, risperidone and l-name

Involvement of NO/cGMP pathway in the antidepressant-like effect of gabapentin in mouse forced swimming test

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