Systemic morphine produce antinociception mediated by spinal 5‐HT7, but not 5‐HT1A and 5‐HT2 receptors in the spinal cord

Doğrul, Ahmet; Seyrek, Melik

doi:10.1038/sj.bjp.0706854

Cited by 90 publications

(54 citation statements)

References 51 publications

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“…Spinal 5-HT 7 receptors were also involved in the inhibitory effects of milnacipran at this same time point, and contribute to the effects of a variety of other analgesics, including opioids (Dogrul and Seyrek, 2006;Seyrek et al, 2010), and may thus represent a novel target for analgesia. The inhibitory effects of milnacipran were also partly opioid dependent, since spinal administration of naloxone partially reversed these effects.…”

Section: Discussionmentioning

confidence: 99%

The Antinociceptive Effect of Milnacipran in the Monosodium Iodoacetate Model of Osteoarthritis Pain and Its Relation to Changes in Descending Inhibition

Burnham

Dickenson

2013

J Pharmacol Exp Ther

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Osteoarthritis (OA) is a chronic joint disorder whose principal symptom is chronic pain. Current analgesics are inadequate and the mechanisms contributing to this pain are poorly understood but likely to include both local joint changes and central consequences. These studies used monoamine receptor agents combined with behavioral studies and single-unit dorsal horn recordings to examine whether descending noradrenergic and serotonergic inhibitions are altered in the monosodium iodoacetate model of OA pain, and whether increasing these inhibitions with the serotonin/noradrenaline reuptake inhibitor milnacipran can attenuate the attendant hypersensitivity. Early and late in the course of this model, milnacipran (s.c.) reduced behavioral hypersensitivity, and inhibited evoked responses from sensitized dorsal horn neurons. In naïve animals and the early, but not late, phase of the model, spinal administration of the a 2 -adrenoceptor antagonist atipamezole fully reversed this neuronal inhibition, whereas atipamezole administered alone revealed that endogenous noradrenergic inhibition was reduced in the late phase. Blocking spinal 5-hydroxytryptamine-7 receptors with (2R)-1-[(3-hydroxyphenyl) sulfonyl]-2-[2-(4-methyl-1-piperidinyl)ethyl]pyrrolidine hydrochloride suggested that the effects of milnacipran in the late phase were partly mediated by these receptors, and that descending serotonergic inhibition was increased in this phase. An opioidergic mechanism behind the effects of milnacipran was indicated by a partial reversal of these effects with naloxone. These studies demonstrate antinociceptive effects for milnacipran in a model of OA pain, whose effects come via descending serotonergic and noradrenergic, as well as opioidergic, pathways. Variations in the activity of these pathways over the course of this model may contribute to the presence of behavioral hypersensitivity and determine through which endogenous systems milnacipran exerts its effects.

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Section: Discussionmentioning

confidence: 99%

The Antinociceptive Effect of Milnacipran in the Monosodium Iodoacetate Model of Osteoarthritis Pain and Its Relation to Changes in Descending Inhibition

Burnham

Dickenson

2013

J Pharmacol Exp Ther

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“…The antinociceptive effect of morphine administered either systemically or into the rostroventromedial medulla was blocked by intrathecal administration of the selective 5-HT 7 receptor antagonist SB-269970 (1,2). Similarly, intrathecal injection of the 5-HT 7 receptor antagonists SB-269970 and SB-258719 has been recently shown to block the antinociceptive and antihyperalgesic effects of both tramadol and its opioid metabolite M1 (3).…”

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confidence: 90%

Potentiation of Morphine Analgesia by Adjuvant Activation of 5-HT7 Receptors

et al. 2011

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Abstract. Spinal blockade of 5-HT 7 receptors has been reported to inhibit the antinociceptive effect of opioids. In this study, we found that subcutaneous administration of the selective 5-HT 7 receptor agonist E-55888 (10 mg/kg) or the antagonist SB-258719 (5 mg/kg) exerted no effect on the tail-flick test in mice. However, E-55888, but not SB-258719, increased (2.6-fold) the analgesic potency of oral morphine. The potentiating effect exerted by E-55888 was prevented by SB-258719. A pharmacokinetic interaction was discarded as morphine plasma and brain concentrations were not significantly modified when co-administered with E-55888. These results reinforce the involvement of 5-HT 7 receptors in opioid analgesia and point to a potential use of 5-HT 7 receptor agonists as adjuvants of opioid analgesia.

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“…Serotoninergic neurons end in the posterior horn descending from the brain stem, through the dorsolateral funiculus and up to the medulla spinalis (descending inhibitor pathway), where they play a role in the modulation of pain. This event is reversed by serotonin and adrenergic receptor antagonists (4). Metergoline may block the nociceptive effect of mirtazapine through the mechanism described above.…”

Section: Discussionmentioning

confidence: 99%

Antinociceptive Effect of Mirtazapine in Rats with Diabetic Neuropathy

İnal¹,

Büyükşekerci²,

Ulusoy³

2016

Arch Neuropsychiatr

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INTRODUCTIONDiabetic neuropathy is a chronic complication associated with diabetes that has a significant detrimental effect on the daily activities of patients. It occurs in approximately 50% of patients with diabetes within 20 years of diagnosis (1). Different drugs have been used in the treatment of neuropathy, such as tricyclic antidepressants (amitriptyline), selective serotonin reuptake inhibitors (fluoxetine), antiepileptics (carbamazepine, phenytoin), venlafaxine, amantadine, tramadol, oxycodone, gabapentin, bupropion, and capsaicin (1). Mirtazapine is a new antidepressant that acts in a manner that is different from other antidepressants and is notable for the low frequency of severe side effects when compared with other antidepressants (2).Mirtazapine blocks the presynaptic α-2 adrenoreceptors in both the central and peripheral nervous systems, while its affinity to α-1 adrenoreceptors is less marked. In addition, it weakly blocks serotonin-1 (5-hydroxytryptamine-1, 5-HT-1) receptors and strongly blocks 5-HT-2 and 5-HT-3 receptors. On the other hand, it has no effect on noradrenaline re-uptake and does not block the subtypes of β-adrenergic receptors to any significant degree (2).Mirtazapine, with its low side-effect profile, might be considered a good alternative in the treatment of diabetic neuropathy. This study investigated the antinociceptive effect of mirtazapine on diabetic neuropathy in rats and the role of opioidergic, serotoninergic, and adrenergic systems in this effect. Naloxone, a competitive opioid µ (mu) receptor antagonist that removes the respiratory depression effect resulting from opioid toxicity, was used to evaluate the role of the opioidergic system (3). Furthermore, a non-selective serotonin receptor antagonist, metergoline (4), and a α-2a adrenergic receptor antagonist, BRL44408 (5), were used to evaluate the roles of the serotoninergic and adrenergic systems, respectively. METHODSThis study was approved by the Local Ethics Board of Animal Research. Sprague Dawley rats weighing 170-225 g were used in the study. They were divided into 11 groups, each containing four males and four females. Rats were kept in a 12-h daylight and 12-h darkness cycle at a room temperature of 20°C and a humidity of 50%-60% and were administered standard pellet feed and water. Rats were brought to the experiment area 1 h prior to the start of experiments to enable them to adjust to the environment. Sensorimotor PerformanceA rotarod test was used to detect the motor activity of rats to be included in the study, with the adequacy of motor activity being defined as being able to stay on the rod for at least 120 s. Introduction: To evaluate the antinociceptive effect of mirtazapine and the mechanisms mediating this effect in neuropathic pain in rats with diabetes.

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Systemic morphine produce antinociception mediated by spinal 5‐HT₇, but not 5‐HT_1A and 5‐HT₂ receptors in the spinal cord

Cited by 90 publications

References 51 publications

The Antinociceptive Effect of Milnacipran in the Monosodium Iodoacetate Model of Osteoarthritis Pain and Its Relation to Changes in Descending Inhibition

The Antinociceptive Effect of Milnacipran in the Monosodium Iodoacetate Model of Osteoarthritis Pain and Its Relation to Changes in Descending Inhibition

Potentiation of Morphine Analgesia by Adjuvant Activation of 5-HT7 Receptors

Antinociceptive Effect of Mirtazapine in Rats with Diabetic Neuropathy

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