PhD Scientific Days 2019

Budapest, April 25–26, 2019

The analgesic effect of sarcosine, a glycine transporter-1 inhibitor in nociceptive and neuropathic pain in rats

Amir, Mohammadzadeh

Amir Mohammadzadeh
Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest.

Language of the presentation

English

Text of the abstract

Introduction: Recently growing data support the analgesic action of the glycine transporter inhibitors. However, controversial data have also been reported on their antinociception. Therefore, GlyT-1 inhibitors might be promising analgesic agents, especially for the treatment of neuropathic pain.

Aims: Investigation of the effects of the GlyT-1 inhibitor sarcosine after acute and chronic treatment: 1) acute nociceptive thermal test: tail-flick test; 2) acute inflammatory model: formalin test; 3) mononeuropathic model.

Methods: Male Wistar rats (150-300 g) were used. Tail-flick test: the tail-flick reaction was evoked by a light focused on the tail of rats. The reaction time was expressed in Sec. Measurements were carried out before and after acute-, and chronic (3 and 7 days, twice daily) treatments. Formalin test: 2.5% formalin was injected into the right hind paw and nociceptive reactions were calculated for 60 min. Sarcosine’s effect was assessed following acute or 3 days of treatment. Mononeuropathic model: Right side sciatic nerve was partially ligated (Seltzer ligation). Tactile sensitivity was tested by dynamic plantar aesthesiometer. Sarcosine effect was determined after acute-, 3 and 5 days of treatment. The drug or vehicle was subcutaneous (sc.) injected.

Results: Systemic sarcosine (1000 mg/kg) showed significant antinociception in rat tail-flick assay following 3 and 7 days of treatment. Sarcosine failed to affect pain reactions in Formalin test. Systemic sarcosine (500 mg/kg) showed antiallodynic effect in mononeuropathic pain model after acute, 3 and 5 days of treatment. In addition, no effect was measured in the intact paws.

Conclusion: Acute GlyT-1 inhibition does not alleviate thermal pain, however, chronic GlyT-1 inhibition results in thermal antinociception. In neuropathic model, both acute and chronic treatment successfully alleviated mechanical allodynia. These data suggest that GlyT-1 might be a novel therapeutic target in the treatment of neuropathic pain, which is still a huge clinical challenge.

Data of the presenter

Doctoral School: Doctoral school of pharmaceutical sciences
Program: Experimental and Clinical Pharmacology
Supervisor: Mahmoud Alkhrasani
E-mail address: al-khrasani.mahmoud@med.semmelweis-univ.hu