Noradrenergic and opioidergic influences on the antinociceptive effect of clomipramine in the formalin test in rats

Ansuategui, Miguel; Naharro, Luis; Feria, Manuel

doi:10.1007/bf00442012

Cited by 34 publications

(15 citation statements)

References 26 publications

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“…Many studies have reported the inhibition of antinociceptive effect of ADs by naloxone but exclusively after acute (Michael-Titus and Costentin, 1987;Ardid and Guilbaud, 1992;Valverde et al, 1994;Gray et al, 1998) or daily and twice daily administrations (Ansuategui et al, 1989) in different pain tests and models. The total inhibition of the effect demonstrates that CMI needs a functional opioid system to induce its antihyperalgesic effect in conditions of repeated treatment in a model of neuropathic pain.…”

Section: Discussionmentioning

confidence: 99%

Evidence for an Involvement of Supraspinal δ- and Spinal μ-Opioid Receptors in the Antihyperalgesic Effect of Chronically Administered Clomipramine in Mononeuropathic Rats

Marchand

Ardid²,

Chapuy³

et al. 2003

J Pharmacol Exp Ther

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The mechanisms of involvement of the opioidergic system in the antinociceptive effect of antidepressants remain to be elucidated. The present study was designed to determine what type of opioid receptors may be involved at the spinal and supraspinal levels in the antihyperalgesic effect of clomipramine, a tricyclic antidepressant commonly prescribed in the treatment of neuropathic pain. Its antihyperalgesic effect on mechanical hyperalgesia (paw pressure test) in rats induced by chronic constriction injury of the sciatic nerve was assessed after repeated administrations (five injections every half-life, a regimen close to clinical use). Naloxone administered at a dose of 1 mg/kg i.v., which blocks all opioid receptors, or at a low dose of 1 g/kg i.v., which selectively blocks the -opioid receptor, inhibited the antihyperalgesic effect of clomipramine and hence indicated that -opioid receptor is involved. Depending on whether they are administered by the intracerebroventricular or intrathecal route, specific antagonists of the various opioid receptor subtypes [D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-ThrNH 2 (CTOP), ; naltrindole (NTI), ␦; and nor-binaltorphimine (nor-BNI), ] differently modify the antihyperalgesic effect of chronically injected clomipramine. The effect was inhibited by intrathecal administration of CTOP and intracerebroventricular administration of naltrindole, whereas nor-BNI was ineffective whatever the route of injection. These results demonstrate a differential involvement of opioid receptors according to the level of the central nervous system: ␦-receptors at the supraspinal level and -receptors at the spinal level. Clomipramine could act via a neuronal pathway in which these two receptors are needed.

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Section: Discussionmentioning

confidence: 99%

Evidence for an Involvement of Supraspinal δ- and Spinal μ-Opioid Receptors in the Antihyperalgesic Effect of Chronically Administered Clomipramine in Mononeuropathic Rats

Marchand

Ardid²,

Chapuy³

et al. 2003

J Pharmacol Exp Ther

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“…Moreover, this enhanced antinociceptive effect was replicated with the selective serotonin uptake inhibitor fluoxetine, but not with dopamine or norepinephrine transporter inhibitors, suggesting that the effect depended on serotonin transporter inhibition (Gatch et al, 1998). Clomipramine has also been shown to enhance the antinociceptive effects of morphine in rodents (Kellstein et al, 1984;Ansuategui et al, 1989;Sierralta et al, 1995). Overall, these studies suggest further research on mu agonist and serotonin uptake inhibitor drug mixtures as candidate analgesics is warranted.…”

Section: Introductionmentioning

confidence: 93%

Antinociceptive Interactions between Mu-Opioid Receptor Agonists and the Serotonin Uptake Inhibitor Clomipramine in Rhesus Monkeys: Role of Mu Agonist Efficacy

Banks

Rice²,

Negus³

2010

J Pharmacol Exp Ther

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Mu-opioid agonists are effective analgesics but have undesirable effects such as sedation and abuse liability that limit their clinical effectiveness. Serotonergic systems also modulate nociception, and serotonin uptake inhibitors may be useful as adjuncts to enhance analgesic effects and/or attenuate undesirable effects of mu agonists. This study examined the effects of the serotonin uptake inhibitor clomipramine on behavioral effects produced in rhesus monkeys by mu agonists with varying efficacy at mu receptors (nalbuphine Ͻ morphine Ͻ methadone). Clomipramine and each mu agonist were studied alone and in fixed-proportion mixtures in assays of schedule-controlled responding, thermal nociception, and capsaicin-induced thermal allodynia. In the assay of schedule-controlled responding, all mu agonists dose-dependently decreased response rates. Clomipramine was inactive alone and did not alter the effects of mu agonists. In the assay of thermal nociception, all mu agonists produced dose-dependent antinociception. Clomipramine was inactive alone but produced a proportion-dependent enhancement of the antinociceptive effects of nalbuphine Ͼ morphine Ͼ methadone. In the assay of capsaicin-induced allodynia, nalbuphine produced dose-dependent antiallodynia. Clomipramine alone was inactive, but as in the assay of thermal nociception, it produced a proportion-dependent enhancement in the effects of nalbuphine. These findings suggest that serotonin uptake inhibitors can selectively enhance the antinociceptive effects of mu agonists in nonhuman primates. These effects of serotonin uptake inhibitors may depend on the proportion of the serotonin uptake inhibitor and the efficacy of the mu agonist. The greatest enhancement was observed with intermediate proportions of clomipramine in combination with the low-efficacy mu agonist nalbuphine.

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“…In contrast, coadministration of either doxepin or venlafaxine with morphine made it less effective in attenuation of neuropathic pain symptoms. The analgesic action of antidepressants after local administration deserves further study due to the first and only experimental and clinical data that focused on the analgesic efficacy of antidepressants after different methods of administration (oral, subcutaneous, intraperitoneal, intrathecal, topical) in different models of pain [9,15,[35][36][37][38]. The analgesic effect of antidepressants is different from their action as a mood elevator.…”

Section: Discussionmentioning

confidence: 99%

Analgesic effects of antidepressants alone and after their local co-administration with morphine in a rat model of neuropathic pain

Jagła

Mika

Makuch

et al. 2014

Pharmacological Reports

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(2014) 'Analgesic eects of antidepressants alone and after their local co-administration with morphine in a rat model of neuropathic pain.', Pharmacological reports., 66 (3). pp. 459-465. Further information on publisher's website: Additional information: Use policyThe full-text may be used and/or reproduced, and given to third parties in any format or medium, without prior permission or charge, for personal research or study, educational, or not-for-prot purposes provided that:• a full bibliographic reference is made to the original source • a link is made to the metadata record in DRO • the full-text is not changed in any way The full-text must not be sold in any format or medium without the formal permission of the copyright holders.Please consult the full DRO policy for further details. IntroductionNeuropathic pain is defined as pain arising as a direct consequence of a lesion or disease affecting the somatosensory system [1]. The most frequent etiologic factors of neuropathic pain are trauma (including post-surgery scars), metabolic disturbances (e.g., diabetes mellitus) and ischemia. The pathological mechanism of neuropathic pain differs significantly from that of inflammatory pain; studies have shown that the changes in spinal gene expression under neuropathy and inflammations are different [2]. Thus, the response to antinociceptive drugs, especially opioids, is not the same. It has generally been accepted that neuropathic pain is somewhat resistant to morphine administration in clinical studies [3,4], and the reduced ability of morphine to attenuate allodynia and hyperalgesia in experimental models of neuropathic pain has been demonstrated [5][6][7][8]. For these reasons, it is a common clinical practice to use analgesic drug combinations. The primary approach to treat neuropathic pain is the use of coanalgesics such as tricyclic antidepressants (TCA); however, their systemic application is associated with significant side effects, which can hinder the desired analgesic effect. An alternative approach to this is the topical administration of analgesics. Currently, the possibility of the topical Background:The therapy of neuropathic pain may include the use of co-analgesics, such as antidepressants, however, their desired analgesic effect is associated with significant side effects. An alternative approach to this is their local administration which has been proposed, but there is little data regarding their local co-administration with morphine and the nature of the interaction between morphine and either doxepin or venlafaxine, two antidepressant drugs that have been recently used in neuropathic pain therapies. Methods: This study was performed on rats after chronic constriction injury (CCI) to the sciatic nerve. The von Frey and Hargreaves' tests were used to assess mechanical allodynia and thermal hyperalgesia, respectively, after intraplantar (ipl) or subcutaneous (sc) administration of amitriptyline, doxepin, or venlafaxine, or their ipl co-administration with morphine on day 12-16 after inj...

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Noradrenergic and opioidergic influences on the antinociceptive effect of clomipramine in the formalin test in rats

Cited by 34 publications

References 26 publications

Evidence for an Involvement of Supraspinal δ- and Spinal μ-Opioid Receptors in the Antihyperalgesic Effect of Chronically Administered Clomipramine in Mononeuropathic Rats

Evidence for an Involvement of Supraspinal δ- and Spinal μ-Opioid Receptors in the Antihyperalgesic Effect of Chronically Administered Clomipramine in Mononeuropathic Rats

Antinociceptive Interactions between Mu-Opioid Receptor Agonists and the Serotonin Uptake Inhibitor Clomipramine in Rhesus Monkeys: Role of Mu Agonist Efficacy

Analgesic effects of antidepressants alone and after their local co-administration with morphine in a rat model of neuropathic pain

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