Anti-nociception is selectively enhanced by parallel inhibition of multiple subtypes of monoamine transporters in rat models of persistent and neuropathic pain

Pedersen, Louise H.; Nielsen, Alexander Norup; Blackburn-Munro, Gordon

doi:10.1007/s00213-005-0120-6

Cited by 85 publications

(55 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This is the first study to describe the antiallodynic effects of nalbuphine in nonhuman primates, although nalbuphine was shown to be effective in some rat models of inflammatory pain (Lomas et al, 2007;Ortiz et al, 2007;Ortiz and Castañ eda-Herná ndez, 2008). Clomipramine produced little or no effect up to the highest dose tested in all three assays, which agrees with previous studies in finding that clomipramine and other serotonin uptake inhibitors produce little effect on rates of schedule-controlled responding or thermal nociception in nonhuman primates (Kleven and Woolverton, 1993;Spealman, 1993;Gatch et al, 1998) or pain-related behaviors in rodent models of inflammatory pain (Pedersen et al, 2005).…”

Section: Discussionsupporting

confidence: 84%

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

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionsupporting

confidence: 84%

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

View full text Add to dashboard Cite

show abstract

“…In contrast to both tricyclic antidepressants, venlafaxine did not reverse thermal hyperalgesia, but attenuation of allodynia was observed at all of the time points with statistical significance measured only at the highest dose (25 mg). This result is inconsistent with the results obtained in 2005 by Pedersen et al [43] in which venlafaxine was ineffective against mechanical allodynia in CCI and spinal nerve ligation models. This study also reported that venlafaxine transiently increased the tail-flick latency in uninjured animals and attenuated second-phase flinching in the formalin test in rats [43].…”

Section: Discussioncontrasting

confidence: 99%

“…This result is inconsistent with the results obtained in 2005 by Pedersen et al [43] in which venlafaxine was ineffective against mechanical allodynia in CCI and spinal nerve ligation models. This study also reported that venlafaxine transiently increased the tail-flick latency in uninjured animals and attenuated second-phase flinching in the formalin test in rats [43]. Interestingly, Lang et al [21] has shown that venlafaxine administered per os in the CCI model prevented the development of chronic pain if it was administered before the constriction to the sciatic nerve and reversed pain if it was given after, which is in agreement with our results.…”

Section: Discussioncontrasting

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

View full text Add to dashboard Cite

(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...

show abstract

“…Dual NET and SERT inhibitors, such as the tricyclic antidepressants (TCAs) amitriptyline and desipramine (Owens et al, 1997), possess greater analgesic efficacy, particularly in painful neuropathic states such as herpes neuralgia, diabetic neuropathy, and nerve crush syndromes (Sindrup et al, 2005), than either selective NET or SERT inhibitors (Fishbain et al, 2000). Likewise, the contribution of dopaminergic pathways to analgesic processes is supported by observations that dopamine transport (DAT) inhibitors (Pedersen et al, 2005) and D 2 agonists (Magnusson and Fisher, 2000) are antinociceptive in models of acute and chronic pain elicited by a number of modalities. Clinical evidence of a role for DA in modulating nociceptive inputs is provided by the hyperalgesia associated with dopaminergic hypofunction, such as in Parkinson's disease (Drake et al, 2005), whereas the DAT inhibitor bupropion (Semenchuk and Davis, 2000) and the DA precursor levodopa (Ertas et al, 1998) are analgesic in neuropathic pain syndromes (Hagelberg et al, 2004).…”

mentioning

confidence: 99%

“…Dual uptake inhibitors, such as venlafaxine and duloxetine, which are clinically effective in reducing neuropathic pain (Lang et al, 1996;Iyengar et al, 2004), have mitigated many of these limiting side effects. However, enhancement of dopaminergic neurotransmission may further expand the favorable analgesic profile of dual NET and SERT inhibitors (Pedersen et al, 2005). To this end, we have characterized the antinociceptive properties of bicifadine (1-p-tolyl-3-azabicyclo[3.1.0]hexane), an inhibitor of biogenic amine transporters, in animal models of acute and chronic pain.…”

mentioning

confidence: 99%

Characterization of the Antinociceptive Actions of Bicifadine in Models of Acute, Persistent, and Chronic Pain

Basile¹,

Janowsky²,

Gołembiowska

et al. 2007

J Pharmacol Exp Ther

View full text Add to dashboard Cite

Bicifadine (1-p-tolyl-3-azabicyclo[3.1.0]hexane) inhibits monoamine neurotransmitter uptake by recombinant human transporters in vitro with a relative potency of norepinephrine Ͼ serotonin Ͼ dopamine (Ϸ1:2:17). This in vitro profile is supported by microdialysis studies in freely moving rats, where bicifadine (20 mg/kg i.p.) increased extrasynaptic norepinephrine and serotonin levels in the prefrontal cortex, norepinephrine levels in the locus coeruleus, and dopamine levels in the striatum. Orally administered bicifadine is an effective antinociceptive in several models of acute, persistent, and chronic pain. Bicifadine potently suppressed pain responses in both the Randall-Selitto and kaolin models of acute inflammatory pain and in the phenyl-p-quinone-induced and colonic distension models of persistent visceral pain. Unlike many transport inhibitors, bicifadine was potent and completely efficacious in both phases of the formalin test in both rats and mice. Bicifadine also normalized the nociceptive threshold in the complete Freund's adjuvant model of persistent inflammatory pain and suppressed mechanical and thermal hyperalgesia and mechanical allodynia in the spinal nerve ligation model of chronic neuropathic pain. Mechanical hyperalgesia was also reduced by bicifadine in the streptozotocin model of neuropathic pain. Administration of the D 2 receptor antagonist (Ϫ)-sulpiride reduced the effects of bicifadine in the mechanical hyperalgesia assessment in rats with spinal nerve ligations. These results indicate that bicifadine is a functional triple reuptake inhibitor with antinociceptive and antiallodynic activity in acute, persistent, and chronic pain models, with activation of dopaminergic pathways contributing to its antihyperalgesic actions.Multiple neurotransmitters have been implicated in the modulation of nociceptive signaling at both the spinal and supraspinal levels of central nervous system processing (Millan, 2002). Among these, norepinephrine (NE) and serotonin (5-HT) play important roles in modulating nociceptive information via pathways descending from the brainstem to the level of the dorsal horn. Noradrenergic fibers from the locus coeruleus and subcoeruleus descend Article, publication date, and citation information can be found at

show abstract

Anti-nociception is selectively enhanced by parallel inhibition of multiple subtypes of monoamine transporters in rat models of persistent and neuropathic pain

Cited by 85 publications

References 56 publications

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

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

Characterization of the Antinociceptive Actions of Bicifadine in Models of Acute, Persistent, and Chronic Pain

Contact Info

Product

Resources

About