PhD Scientific Days 2026

Poster Session 2.M - Neurosciences

Glycine Transporter 1 Inhibitors Minimize the Analgesic Tolerance to Morphine in Rats

Előadó neve

Galambos, Anna

Neptune code

RKOOXL

Előadó munkahelye

SE Department of Pharmacology and Pharmacotherapy

Előadó telefonszáma

06306444796

Előadó e-mail címe

galambosanna50@gmail.com

Az előadás címe

Glycine Transporter 1 Inhibitors Minimize the Analgesic Tolerance to Morphine in Rats

Szerző(k) neve és munkahelye

Anna Rita Galambos¹, Nariman Essmat¹, Péter P. Lakatos², Imre Boldizsár, Jr.¹, Dávid Á. Karádi¹, Sarah Kadhim Abbood¹, Kornél Király¹, Pál Riba¹, Tamás Tábi², Laszlo G. Harsing, Jr.¹, Ferenc Zádor¹, Mahmoud Al-Khrasani¹

1: SE Department of Pharmacology and Pharmacotherapy
2: SE Department of Pharmacodynamics

Bemutatás módja

Poszter

Szekció

Poster Session 2.M - Neurosciences

Language of the presentation

English

Preferred session

Neurosciences

Összefoglaló szövege

Introduction: Opioid analgesics are a cornerstone in managing mild to severe acute and chronic pain, however their long term-application is limited by side effects. The majority of currently prescribed opioid analgesics target μ-opioid receptors (MORs). Prolonged use of MOR agonists develops analgesic tolerance, dose escalation is required to retain the opioid analgesic efficacy consequently increasing the side effects. Many attemts have been made to delay tolerance development, but none have proven clinically significant. Thus, exploring new treatment avenues is crucial for chronic pain patients. Recent research indicates that glycine transporter-1 (GlyT1) inhibitors have potential in halting neuropathic pain, which shares certain spinal mechanisms with opioid tolerance such as iNMDARs' activation.
Aims: Investigating the involvement of the spinal glycinergic system in morphine analgesic tolerance development and examining the impact of the selective GlyT1 inhibitor NFPS on opioid antinociceptive tolerance following repeated morphine administration.
Methods: In vivo and in vitro studies were applied to measure tolerance and NFPS effect. The rat tail-flick assay, a thermal pain model was utilized, where male Wistar rats (170-230g) received sc. morphine, NFPS or their combination for 10 days. Pain threshold was measured before and after treatment. After 10 days, cerebrospinal fluid (CSF) glycine levels were measured using capillary electrophoresis. Motor function was assessed by the rotarod test. Spinal cord MOR protein expression was measured by Western blot.
Results: Acute morphine treatment (10 mg/kg) produced in significant antinociceptive effects, but high degree of tolerance was measured after 10 days. NFPS failed to show antinociception alone but significantly delayed morphine tolerance when co-administered chronically at 0.6 mg/kg. CSF glycine levels increased following NFPS treatment. Chronic treatment with NFPS did not affect the motor function of the animals. MOR protein expression did not change significantly.
Conclusions: Co-administration of GlyT1 inhibitors and opioid analgesics maintains antinociceptive effect of opioids. The observed effect could be related to the regulation of glycine at the vicinity of spinal iNMDARs, in particular the extrasynaptic GluN2B which is implicated in the mechanism for opioid analgesic tolerance.
Fund: FK_138389

University

Semmelweis University

Supervisor

Dr. Al-Khrasani Mahmoud, Dr. Király Kornél

Publication of my abstract

I do not give consent to the publication of my abstract on the website of the congress.

phd.section.field

after finishing doctoral studies with absolutorium (PhD)

Kind

Szabad

Status

elfogadva

Accepted presentation method

poszter

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

7404

Start

18:18

End

18:21