Testing of analgesic effect of fluoxetine

Begović, Amra; Zulić, Irfan; Bečić, Fahir

doi:10.17305/bjbms.2004.3367

Cited by 9 publications

(5 citation statements)

References 3 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Antidepressant drugs are reported to be used as co-analgesics in clinical management of migraine and neuropathic pain [45], [46]. Several studies have reported that a selective serotonin reuptake inhibitor, fluoxetine, produces an antinociceptive effect in pain assays, including the hot plate test [47], [48]. In our experiments, DKO animals exhibited altered pain sensitivity to an acute thermal stimulus in the hot plate model supporting 5-HT involvement in the regulation of pain.…”

Section: Discussionsupporting

confidence: 76%

Genetic Disruption of Both Tryptophan Hydroxylase Genes Dramatically Reduces Serotonin and Affects Behavior in Models Sensitive to Antidepressants

et al. 2008

View full text Add to dashboard Cite

The neurotransmitter serotonin (5-HT) plays an important role in both the peripheral and central nervous systems. The biosynthesis of serotonin is regulated by two rate-limiting enzymes, tryptophan hydroxylase-1 and -2 (TPH1 and TPH2). We used a gene-targeting approach to generate mice with selective and complete elimination of the two known TPH isoforms. This resulted in dramatically reduced central 5-HT levels in Tph2 knockout (TPH2KO) and Tph1/Tph2 double knockout (DKO) mice; and substantially reduced peripheral 5-HT levels in DKO, but not TPH2KO mice. Therefore, differential expression of the two isoforms of TPH was reflected in corresponding depletion of 5-HT content in the brain and periphery. Surprisingly, despite the prominent and evolutionarily ancient role that 5-HT plays in both vertebrate and invertebrate physiology, none of these mutations resulted in an overt phenotype. TPH2KO and DKO mice were viable and normal in appearance. Behavioral alterations in assays with predictive validity for antidepressants were among the very few phenotypes uncovered. These behavioral changes were subtle in the TPH2KO mice; they were enhanced in the DKO mice. Herein, we confirm findings from prior descriptions of TPH1 knockout mice and present the first reported phenotypic evaluations of Tph2 and Tph1/Tph2 knockout mice. The behavioral effects observed in the TPH2 KO and DKO mice strongly confirm the role of 5-HT and its synthetic enzymes in the etiology and treatment of affective disorders.

show abstract

Section: Discussionsupporting

confidence: 76%

Genetic Disruption of Both Tryptophan Hydroxylase Genes Dramatically Reduces Serotonin and Affects Behavior in Models Sensitive to Antidepressants

et al. 2008

View full text Add to dashboard Cite

show abstract

“…For example, citalopram produces antinociceptive effects in both rats [222-224] and mice [219,225]. Such antinociceptive behaviors were reported with other SSRIs such as fluoxetine [226,227], fluvoxamine [219,222,228], paroxetine and sertraline [229-232] (Table 3). Interestingly, the effects of fluoxetine are completely blunted in 5-HT depleted animals [227,233] suggesting that SSRIs-induced antinociception involves serotonergic pathways.…”

Section: Monoamines Reuptake Inhibitors and Pain Preclinical Outcomesmentioning

confidence: 80%

Monoaminergic Antidepressants in the Relief of Pain: Potential Therapeutic Utility of Triple Reuptake Inhibitors (TRIs)

et al. 2011

View full text Add to dashboard Cite

Over 75% of depressed patients suffer from painful symptoms predicting a greater severity and a less favorable outcome of depression. Imaging, anatomical and functional studies have demonstrated the existence of common brain structures, neuronal pathways and neurotransmitters in depression and pain. In particular, the ascending serotonergic and noradrenergic pathways originating from the raphe nuclei and the locus coeruleus; respectively, send projections to the limbic system. Such pathways control many of the psychological functions that are disturbed in depression and in the perception of pain. On the other hand, the descending pathways, from monoaminergic nuclei to the spinal cord, are specifically implicated in the inhibition of nociception providing rationale for the use of serotonin (5-HT) and/or norepinephrine (NE) reuptake inhibitors (SSRIs, NRIs, SNRIs), in the relief of pain. Compelling evidence suggests that dopamine (DA) is also involved in the pathophysiology and treatment of depression. Indeed, recent insights have demonstrated a central role for DA in analgesia through an action at both the spinal and suprasinal levels including brain regions such as the periaqueductal grey (PAG), the thalamus, the basal ganglia and the limbic system. In this context, dopaminergic antidepressants (i.e., containing dopaminergic activity), such as bupropion, nomifensine and more recently triple reuptake inhibitors (TRIs), might represent new promising therapeutic tools in the treatment of painful symptoms with depression. Nevertheless, whether the addition of the dopaminergic component produces more robust effects than single- or dual-acting agents, has yet to be demonstrated. This article reviews the main pathways regulating pain transmission in relation with the monoaminergic systems. It then focuses on the current knowledge regarding the in vivo pharmacological properties and mechanism of action of monoaminergic antidepressants including SSRIs, NRIs, SNRIs and TRIs. Finally, a synthesis of the preclinical studies supporting the efficacy of these antidepressants in analgesia is also addressed in order to highlight the relative contribution of 5-HT, NE and DA to nociception.

show abstract

“…In addition, we reported here the existence of a direct correlation between despair behaviour and enhanced pain sensitivity (Figure 7(b)), indicating a higher sensitivity to the antidepressant treatment in sciatic-operated mice, in which an enhanced pain sensitivity was observed. Both acute and chronic fluoxetine treatment were reported to elicit antinociceptive effects (Begović et al, 2004; Singh et al, 2001) in addition to its antidepressant properties in a mouse model of anxiety/depression (David et al, 2009). Furthermore, recent evidence reveals that particular antidepressants attenuated the function of glutamate GluN receptors, suggesting that this mechanism contributes to their therapeutic effects in chronic pain (Micó et al, 2006; Sánchez-Blázquez et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

“…In addition, rats with anxiety-like or despair behaviours, comorbid with chronic neuropathic pain, showed impaired noradrenergic neurotransmission (Alba- Delgado et al, 2013;Bravo et al, 2012Bravo et al, , 2014. Finally, inhibitors of serotonin uptake used as antidepressant compounds also elicit antinociceptive effects in animal models (Begović et al, 2004;Singh et al, 2001;Valverde et al, 1994), and combined serotonin and noradrenaline uptake inhibition conferred increased analgesic benefits (Maletic and Raison, 2009). Thence, we decided to analyse the existence of serotonergic neurotransmission alterations in the PFC related to neuropathic pain.…”

Section: Analytementioning

confidence: 99%

Chronic pain causes a persistent anxiety state leading to increased ethanol intake in CD1 mice

et al. 2015

View full text Add to dashboard Cite

Mood disorders and chronic pain are closely linked, but limited progress has been made in understanding the role of chronic and neuropathic pain in the aetiopathogenesis of depression. To explore the pathological mechanisms that mediate the association between pain and depressive-like behaviours, we studied the time-dependent effect of neuropathic pain on the development of anxiety-like and despair behaviours in CD1 mice. We analysed behavioural data, neuroinflammation reactions and changes in neurotransmitter (glutamate and serotonin) levels in the mouse prefrontal cortex. Sciatic-operated mice displayed long-lasting anxiety-like and despair behaviours, starting 5 and 20 days after partial sciatic nerve ligation, respectively. Glutamatergic neurotransmission and IL-1β cytokine expression were enhanced in the prefrontal cortex of mice with neuropathic pain. We found no change in serotonin metabolism, cytokine IL-6 or brain-derived neurotrophic factor levels. While sciatic-operated mice exposed to intermittent ethanol intake (20% v/v) using the drinking in the dark procedure consumed higher amounts of ethanol than sham-operated mice, thermal allodynia and despair behaviour were not attenuated by ethanol consumption. Our findings reveal an association between glutamatergic neurotransmission and pain-induced mood disorders, and indicate that moderate ethanol consumption does not relieve nociceptive and depressive behaviours associated with chronic pain in mice.

show abstract

Testing of analgesic effect of fluoxetine

Cited by 9 publications

References 3 publications

Genetic Disruption of Both Tryptophan Hydroxylase Genes Dramatically Reduces Serotonin and Affects Behavior in Models Sensitive to Antidepressants

Genetic Disruption of Both Tryptophan Hydroxylase Genes Dramatically Reduces Serotonin and Affects Behavior in Models Sensitive to Antidepressants

Monoaminergic Antidepressants in the Relief of Pain: Potential Therapeutic Utility of Triple Reuptake Inhibitors (TRIs)

Chronic pain causes a persistent anxiety state leading to increased ethanol intake in CD1 mice

Contact Info

Product

Resources

About