PhD Scientific Days 2023

Budapest, 22-23 June 2023

Pharmaceutical Sciences - Posters F

Tolperisone-Pregabalin Combination Alleviates Pain in Rats with Peripheral Mononeuropathy

Nariman Essmat1, Anna R. Galambos1, Péter P. Lakatos2, David Á. Karádi1, Sarah K. Abbood1, Zoltán S Zádori1, Kornél Király1, Éva Szökő2, Tamás Tábi2, Mahmoud Al-Khrasani1
1Department of Pharmacology and Pharmacotherapy, Semmelweis University, 4 Nagyvárad tér, Budapest, H-1089, Hungary.
2Department of Pharmacodynamics, Semmelweis University, 4 Nagyvárad tér, Budapest, H-1089, Hungary.

Text of the abstract

Introduction: Neuropathic pain (NP) treatment is not fully solved yet. Novel mono- or combined-based therapy approaches are required to produce optimal analgesia of rapid onset and with limited adverse effects.
Aim: To investigate the antiallodynic effect of tolperisone and pregabalin alone or in combination in partial sciatic nerve ligation (pSNL)-induced mono-NP. The impact of these treatments on motor function was also investigated.
Methods: The antiallodynic effect of oral tolperisone and pregabalin (both at 25, 50, and 100 mg/kg), was investigated in male Wistar rats with mono-neuropathy evoked by pSNL. The drugs were administered acutely on day 7 or 14 after the operation and pain assessments were performed 1, 2, and 3 h thereafter. In chronic treatment experiments, the treatment was started on day 7 and continued for two weeks. The allodynia was determined on days 14 and 21 following the operation. Next, the effect of oral tolperisone and pregabline combination (both at 25 mg/kg), was investigated on day 14 after the operation. Allodynia was assessed by dynamic plantar aesthesiometer (DPA). Rotarod test was used to determine the motor function following acute oral treatment with tolperisone (150 mg/kg), pregabalin (25 and 50 mg/kg), and their combination (both at 25 mg/kg).
Results: Neither tolperisone nor pregabalin showed antiallodynic effect after acute oral treatment. However, 100 mg/kg of tolperisone and 50 mg/kg of pregabalin produced a significant antiallodynic effect after 14 consecutive days of treatments. Acute treatment with the combination exerted a significant antiallodynic effect of rapid onset. In the rotarod test, acute oral tolperisone at a dose of 150 mg/kg failed to induce motor dysfunction. Pregabalin produced motor dysfunction following 50 mg/kg administration. Interestingly, the combination of 25 mg/kg tolperisone and 25 mg/kg pregabalin did not induce motor dysfunction.
Conclusions: Tolperisone or pregabalin alone produces analgesia only after chronic treatment. As a novel finding, the combination composed of lower doses of both tolperisone and pregabalin provides antiallodynic effect of fast onset and is devoid of motor dysfunction. Thus, this finding implies that this combination might create future satisfaction with respect to NP therapy.
Funding: The present work was supported by 2018-1.3.1-VKE-2018-00030 project.
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- Name of the University and Doctoral School: Semmelweis University, Doctoral school of pharmaceutical sciences
- Name of the Supervisor: Mahmoud Al Khrasani