Opioid Receptors Contribute to Antinociceptive Effect of Tianeptine on Colorectal Distension-Induced Visceral Pain in Rats

Abstract

Tianeptine is a clinically effective atypical antidepressant with distinct neurochemical properties. In this study, we aimed to investigate the contribution of opioid receptors in the antinociceptive effect of tianeptine on visceral pain in awake rats and to differentiate the subtype and the localization (central and/or peripheral) of these opioid receptors involved in this antinociception. Visceromotor response to noxious colorectal distension (CRD) was quantified with electromyographic recordings, obtained from previously implanted electrodes into the external oblique musculature of rats under anesthesia, before and after tianeptine administration. The opioid receptor antagonist naloxone hydrochloride (NLX) and peripherally restricted opioid receptor antagonist naloxone methiodide (NLXM) were administered intravenously 10 min before tianeptine (10 mg/kg, i.v.). The antinociceptive effect of tianeptine was abolished by NLX (1 and 2 mg/kg, i.v.), but was partially reduced by NLXM (1 and 2 mg/kg, i.v.). A µ-opioid receptor-selective dose (0.03 mg/kg, i.v.) of NLX, but not NLXM, significantly inhibited the antinociceptive effect of tianeptine. Our results suggest that antinociceptive effect of tianeptine on CRD-induced visceral nociception in rats involves the activation of both central and peripheral opioid receptors.

Novel endomorphin analogues CEMR‐1 and CEMR‐2 produce potent and long‐lasting antinociception with a favourable side effect profile at the spinal level

“…administration of CEMR-1 and CEMR-2 produced more potent analgesia than their respective parent peptide in acetic acid-induced visceral pain. A recent investigation reported that antinociceptive effect of the opioids on colorectal distension-induced visceral nociception involved the activation of both central and peripheral opioid receptors (Bilge et al, 2018).…”

Pharmacological interactions between intrathecal pregabalin plus tianeptine or clopidogrel in a rat model of neuropathic pain

“…Recently, an opioid-related mechanism was proposed to explain the antinociceptive effects of tianeptine. Antagonists of all opioid receptor types (μ, δ, and κ) prevented the antinociceptive effect of tianeptine in rats with visceral nociception [ 24 ].…”

“…Previous studies demonstrated synergistic or additive interaction between some drugs [ 25 , 26 ]. It has been reported that the antinociceptive effects of gabapentin and tianeptine were reversed by an opioid receptor antagonist at the spinal level [ 24 , 27 ]. On the other hand, serotonergic and noradrenergic systems are involved in the antinociception of tianeptine, but not that of gabapentin [ 24 , 27 ].…”

“…It has been reported that the antinociceptive effects of gabapentin and tianeptine were reversed by an opioid receptor antagonist at the spinal level [ 24 , 27 ]. On the other hand, serotonergic and noradrenergic systems are involved in the antinociception of tianeptine, but not that of gabapentin [ 24 , 27 ]. These findings suggest that both drugs may have not only a common pharmacologic site of action but also different mechanisms of action.…”

Psychotropic Drugs for the Management of Chronic Pain and Itch

“…In the paper [169], with the help of a radioactively labelled ligand, it was shown in cell cultures from humans and mice that tianeptine is a high-affinity μ-opioid receptor agonist, a medium-affinity full δ-opioid receptor agonist, and is not a κ-opioid receptor agonist. The authors of [170] caused visceral pain in rats by colorectal distension. The antinociceptive effect of tianeptine disappeared after injection of naloxone (opioid receptor antagonist).…”