Effects of tianeptine on the development and maintenance of mechanical allodynia in a rat model of neuropathic pain.

We validate the analgesic efficacy of tianeptine by different administration routes and timing in a rat model of neuropathic pain. Neuropathic pain was induced by ligating the L5 and L6 spinal nerves in male Sprague-Dawley rats, and mechanical allodynia was assessed using von Frey filaments. The effects of orally administered tianeptine and pretreatment with tianeptine (intrathecally or intraperitoneally) on mechanical allodynia were assessed. Oral and preemptive intrathecal administration of tianeptine significantly increased the paw withdrawal threshold but preemptive intraperitoneal administration did not. Nevertheless, intraperitoneal pretreatment of tianeptine potentiated the antiallodynic effects of subsequently administered tianeptine. These findings suggest that tianeptine may be effective for preventing and treating neuropathic pain and that it can be used more widely in clinical pain practice.

Heo BH ，Shin JY ，Park KS ，Lee HG ，Choi JI ，Yoon MH ，Kim WM ... -  《-》

The antiallodynic effect of intrathecal tianeptine is exerted by increased serotonin and norepinephrine in the spinal dorsal horn.

The purpose of this study was to validate the effects of tianeptine on serotonergic and noradrenergic neurotransmission in a rat model of neuropathic pain. Neuropathic pain was induced by ligating the L5 and L6 spinal nerves in male Sprague-Dawley rats, and mechanical allodynia was assessed using von Frey filaments. The effects of intrathecally administered tianeptine on mechanical allodynia were assessed. Dihydroergocristine or yohimbine, a serotonergic or α-2 adrenergic receptor antagonists, respectively, were intrathecally administered 10min before tianeptine to investigate its mechanism of action. Additionally microdialysis studies were performed to measure the extracellular levels of serotonin (5-HT) and norepinephrine (NE) in the spinal dorsal horn following tianeptine administration. Intrathecal tianeptine significantly increased the paw withdrawal thresholds in a dose-dependent manner and the antiallodynic effect was antagonized by dihydroergocristine and yohimbine. Microdialysis studies revealed that tianeptine increased the levels of 5-HT and NE in the spinal dorsal horn. These findings suggest that tianeptine may be effective for the management of neuropathic pain and that its analgesic mechanism is exerted by increased levels of 5-HT and NE in the synaptic cleft at the spinal level.

Lee HG ，Choi JI ，Yoon MH ，Obata H ，Saito S ，Kim WM ... -  《-》

Antiallodynic effect of tianeptine via modulation of the 5-HT7 receptor of GABAergic interneurons in the spinal cord of neuropathic rats.

Although tianeptine, an atypical antidepressant has been reported to have antinociceptive effects, the mode of action is different from that of tricyclic antidepressants despite structural similarities. We examined the antiallodynic effect of intrathecal tianeptine in neuropathic pain rats and determined the involvement of 5-hydroxytryptamine type 7 (5-HT7) receptor of the GABAergic interneurons in the spinal cord. Neuropathic pain was induced by spinal nerve ligation (SNL). After observation of the effect from intrathecal tianeptine, a 5-HT7 receptor antagonist (SB-269970) was administered intrathecally 10 min before delivery of tianeptine, to determine the contribution of spinal 5-HT7 receptor on the activity of tianeptine. GAD expression and GABA concentrations were assessed. Intrathecal tianeptine dose-dependently attenuated mechanical allodynia in SNL rats. Pre-treatment with intrathecal SB-269970 reversed the antiallodynic effect of tianeptine. Both GAD65 expression and the GABA concentration in the spinal cord were decreased in neuropathic rats but were increased by tianeptine. Additionally, 5-HT7 receptor and GAD65 were co-localized in the spinal cord. Intrathecal tianeptine reduces neuropathic pain. 5-HT7 receptor of the GABAergic interneurons together with GAD65 plays a role in the activity of tianeptine at the spinal cord level.

Lin H ，Heo BH ，Kim WM ，Kim YC ，Yoon MH ... -  《-》

Tianeptine Reduces Mechanical Allodynia in Spinal Nerve-ligated and Chemotherapy-induced Neuropathic Mice.

Han SM ，Kim YH ，Jo HU ，Kwak JA ，Park HJ ... -  《-》

The antinociceptive effect of acetaminophen in a rat model of neuropathic pain.

Acetaminophen is one of the most popular and widely used analgesics for the treatment of pain and fever but few studies have evaluated its effects on neuropathic pain. This study examined the effect of acetaminophen on thermal hyperalgesia, mechanical and cold allodynia in a rat model of neuropathic pain. Male Sprague-Dawley rats were prepared by tightly ligating the left L5 and L6 spinal nerves to produce a model of neuropathic pain. Sixty neuropathic rats were assigned randomly into six groups. Normal saline and acetaminophen (25, 50, 100, 200 and 300 mg/kg) were administered intraperitoneally to these individual groups. Thermal hyperalgesia, mechanical and cold allodynia were examined at preadministration and at 15, 30, 60, 90, 120, 180, 240 and 360 min after administering the drug. Mechanical allodynia was quantified by measuring the paw withdrawal threshold to stimuli with von Frey filaments. Cold allodynia was quantified by measuring the frequency of foot lift after applying 100% acetone. Thermal hyperalgesia was quantified by measuring the thermal withdrawal threshold. The rotarod performance was measured to detect any drug-induced adverse effects, such as drowsiness. The hepatic and renal adverse effect was also assessed by measuring the serum levels of aspartate aminotransferase, alanine aminotransferase, blood urea nitrogen and creatinine. The paw withdrawal thresholds to mechanical stimuli and the thermal withdrawal threshold were increased significantly and withdrawal frequencies to cold stimuli were reduced by acetaminophen administration in a dose-dependent manner. Acetaminophen reduces thermal hyperalgesia, mechanical and cold allodynia in a rat model of neuropathic pain, and might be useful for managing neuropathic pain.

Im KS ，Jung HJ ，Kim JB ，Lee JM ，Park HJ ，Joo CH ，Moon DE ... -  《-》