Increased sensitivity of the central nervous system to morphine analgesia by amitriptyline in naive and morphine-tolerant rats

Liu, Shean-Jang; Wang, Richard I. H.

doi:10.1016/0006-2952(81)90229-x

Cited by 39 publications

(5 citation statements)

References 19 publications

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“…On the one hand, the demonstration that TCAS are capable of displacing naloxone from its binding sites in the rat brain (Biegon and Samuel 1980) may suggest that these drugs exert their antinociceptive effect via an interaction with opioid receptors. On the other hand, there is experimental (Malseed and Goldstein 1979;Liu and Wang 1981;Botney and Fields 1983) and clinical (Levine et al 1986) evidence that tertiary amines potentiate the analgesic action of the opiates, so that it could be argued that the antinociceptive effect of clomipramine may be due to an increase in the sensitivity of the CNS to endogenous opioids.…”

Section: Discussionmentioning

confidence: 95%

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

Ansuategui

Naharro²,

Feria³

1989

Psychopharmacology

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Although tricyclic antidepressants are especially useful in the treatment of chronic pain conditions, most of the work about its mechanism of action has been made on acute pain tests. The present study was aimed at studying the role played by noradrenergic and opioidergic influences on the antinociceptive activity of subchronically administered clomipramine in the formalin test (a tonic pain model) in rats. Clomipramine produced antinociception after 7 days, administration (2.5 mg/kg/day), an effect equivalent to that obtained by acute morphine (5 mg/kg). The antinociceptive effect of clomipramine was inhibited by the following: nonspecific blocking of alpha 1- and alpha 2-adrenoceptors by phentolamine, specific blocking of alpha 1-adrenoceptors by prazosin; stimulation of alpha 2 receptors by clonidine; and blocking of the opioid receptors by naloxone. Blocking the alpha 2-receptors with yohimbine did not antagonize the effect of clomipramine. These results suggest that clomipramine produces antinociception in this test, partly via the participation of the endogenous opioid system and partly by further activating or potentiating previously activated noradrenergic pathways which are involved in the control of pain information.

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Section: Discussionmentioning

confidence: 95%

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

Ansuategui

Naharro²,

Feria³

1989

Psychopharmacology

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“…Co-administration of morphine and amitriptyline demonstrated that the interaction between systemic amitriptyline and morphine is synergistic [35]. In addition, it has been stated that amitriptyline treatment prolonged morphine analgesia and decreased morphine tolerance by increasing the sensitivity of the central nervous system to morphine [36]. Other antidepressants, such as fluoxetine and fluvoxamine, were also found to enhance opioid analgesia in other models [37,38].…”

Section: Discussionmentioning

confidence: 99%

The effects of serotonin/norepinephrine reuptake inhibitors and serotonin receptor agonist on morphine analgesia and tolerance in rats

2012

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Several studies have demonstrated that serotonergic and noradrenergic systems have important roles in morphine analgesia and tolerance. However, the exact mechanism underlying the development of morphine tolerance is not fully understood. The aim of this study was to investigate the possible role of serotonin/norepinephrine reuptake inhibitors (amitriptyline, venlafaxine) and serotonin receptor (5-HT(1A) and 5-HT(1B/1D)) agonist (dihydroergotamine) in morphine analgesia and tolerance in rats. To constitute morphine tolerance, animals received morphine (50 mg/kg; s.c.) once daily for 3 days. After the last dose of morphine was injected on day 4, morphine tolerance was evaluated. The analgesic effects of amitriptyline (20 mg/kg; i.p.), venlafaxine (20 mg/kg; s.c.), dihydroergotamine (100 μg/kg; i.v.) and morphine (5 mg/kg) were considered at 15- to 30-min intervals (0, 15, 30, 60, 90, and 120 min) by tail-flick and hot-plate analgesia tests. In this study, the data obtained suggested that amitriptyline and venlafaxine significantly increased the analgesic effect of morphine and attenuated the expression of morphine tolerance. However, dihydroergotamine significantly increased the analgesic effect of morphine but did not reduce the expression of morphine tolerance. In conclusion, we determined that co-administration of morphine with amitriptyline and venlafaxine increased the analgesic effects of morphine and attenuated the morphine analgesic tolerance.

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“…Several TCA compounds (Rigal et al 1983; Taiwo et al 1985; Max et al 1987; Sacerdote et al 1987; Ventafridda et al 1990; Sawynok and Reid 1992; Gatch et al 1998), including amitriptyline (Malseed and Goldstein 1979; Liu and Wang 1981; Botney and Fields 1983; Taiwo et al 1985; Sacerdote et al 1987; Ventafridda et al 1990; Eisenach and Gebhart 1995; Galeotti et al 1996; Luccarini et al 2004), enhance morphine-induced analgesia in animal models. This is consistent with clinical data, which has demonstrated that several TCAs potentiate morphine-induced analgesia in humans (Levine et al 1986; Gordon et al 1993).…”

Section: Discussionmentioning

confidence: 99%

“…Drugs that potentiate the action of 5-HT or NE in the synapse, such as reuptake blockers, potentiate morphine analgesia (Malseed and Goldstein 1979; Liu and Wang 1981; Botney and Fields 1983; Rigal et al 1983; Taiwo et al 1985; Sacerdote et al 1987; Ventafridda et al 1990; Sawynok and Reid 1992; Eisenach and Gebhart 1995; Gatch et al 1998; Luccarini et al 2004). Drugs affecting monoaminergic function also have analgesic properties when administered alone, in particular the tricyclic antidepressants (TCAs; (Pasternak et al 1983; Hwang and Wilcox 1987; Sacerdote et al 1987; Hersh and Kaplan 1990; Tura and Tura 1990; Ventafridda et al 1990; Ardid et al 1991; Acton et al 1992; Ardid et al 1992; Ardid et al 1995; Sawynok et al 1999; Korzeniewska-Rybicka and Plaznik 2000; Sawynok and Reid 2001), including amitriptyline (Spiegel et al 1983; Sacerdote et al 1987; Tura and Tura 1990; Ventafridda et al 1990; Eisenach and Gebhart 1995; Abdi et al 1998; Esser and Sawynok 1999; Sawynok et al 1999; Esser and Sawynok 2000; Korzeniewska-Rybicka and Plaznik 2000; Esser et al 2001; Sawynok and Reid 2001; Heughan and Sawynok 2002; Khan et al 2002; Oatway et al 2003; Luccarini et al 2004; Sudoh et al 2004), which have been shown to be clinically effective analgesics (Watson 1984; Young and Clarke 1985; Levine et al 1986; Max et al 1987; Frank et al 1988; Onghena and Van Houdenhove 1992; Watson et al 1992; Gordon et al 1994; Nicolodi and Sicuteri 1996; Richeimer et al 1997; Gerner et al 2003) also see reviews by (Egbunike and Chaffee 1990; Carter and Sullivan 2002).…”

Section: Introductionmentioning

confidence: 99%

A greater role for the norepinephrine transporter than the serotonin transporter in murine nociception

et al. 2011

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Norepinephrine and serotonin involvement in nociceptive functions is supported by observations of analgesic effects of norepinephrine transporter (NET) and serotonin transporter (SERT) inhibitors such as amitriptyline. However, the relative contribution of NET and SERT to baseline nociception, as well as amitriptyline analgesia, is unclear. Amitriptyline and morphine analgesia in wild-type (WT) mice and littermates with gene knockout (KO) of SERT, NET or both transporters was conducted using the hotplate and tail-flick tests. Hypoalgesia was observed in NET KO mice, and to a lesser extent in SERT KO mice. The magnitude of this hypoalgesia in NET KO mice was so profound that it limited the assessment of drug-induced analgesia. Nonetheless, the necessary exclusion of these subjects because of profound baseline hypoalgesia strongly supports the role of norepinephrine and NET in basal nociceptive behavior while indicating a much smaller role for serotonin and SERT. To further clarify the role of NET and SERT in basal nociceptive sensitivity further experiments were conducted in SERT KO and NET KO mice across a range of temperatures. NET KO mice were again found to have pronounced thermal hypoalgesia compared to WT mice in both the hotplate and tail-flick tests, and only limited effects were observed in SERT KO mice. Furthermore, in the acetic acid writhing test of visceral nociception pronounced hypoalgesia was again found in NET KO mice, but no effect in SERT KO mice. As some of these effects may have resulted from developmental consequences of NET KO, the effects of the selective NET blocker nisoxetine and the selective SERT blocker fluoxetine were also examined in WT mice: only nisoxetine produced analgesia in these mice. Collectively these data suggest that NET has a far greater role in determining baseline analgesia, and perhaps other analgesic effects, than SERT.

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Increased sensitivity of the central nervous system to morphine analgesia by amitriptyline in naive and morphine-tolerant rats

Cited by 39 publications

References 19 publications

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

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

The effects of serotonin/norepinephrine reuptake inhibitors and serotonin receptor agonist on morphine analgesia and tolerance in rats

A greater role for the norepinephrine transporter than the serotonin transporter in murine nociception

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