PhD Scientific Days 2024

Poster Session D - Neurosciences 1.

Tolperisone-Pregabalin Combination: a Promising Therapy for Neuropathic Pain in Rats

Text of the abstract

Introduction: Neuropathic pain (NP) is developed after disease or damage affecting somatosensory neurons. Satisfactory treatment for NP has not been solved thus far due to different etiologies and mechanisms. Finding effective novel agents or combination-based analgesic therapies are needed. The current treatment approaches for NP encompass pregabalin (P) as a first-line medication that affects calcium channels’ function. On the other hand, our recent data showed that tolperisone (T) displays antiallodynic effect in rats with partial sciatic nerve ligation (pSNL) whereas morphine (M) effect was only achieved in high doses.
Aims: To investigate the antiallodynic effect of T, P, and M alone or in combinations in pSNL-induced NP. In addition, to assess the test drugs or combinations in isolated mouse vas deferens (MVD), which hosting calcium and sodium channels as well as µ-opioid receptors.
Methods: The antiallodynic effect of oral T and P (both at 25 mg/kg), M at 3.22 mg/kg alone and in combination, was investigated in male Wistar rats (100-150g) with mono-neuropathy evoked by pSNL.Tactile allodynia was indicated by a decrease in the paw withdrawal threshold (PWT) measured by a dynamic plantar aesthesiometer. The acute effect of test compounds was determined 2 weeks after operation. In vitro assay, MVD experiments used male NMRI mice (35–45g) to assess T and P's efficacy (Emax) compared to that of reference compounds, DAMGO and M. Then, the T, P, or M concentration that produced 20% inhibition was tested in drug combinations.
Results: Both T and P failed to produce an acute antiallodynic effect even in doses up to 100 mg/kg when administered separately. M in high doses produced antinociceptive effect indicated by raising the PWT of both paws. Only the T/P but not T/M combination acutely alleviated allodynia. In vitro, T, P, M, or DAMGO, in a concentration-dependent manner, inhibited the MVD smooth muscle contractions. Emax for T, P, M, or DAMGO was 84.85, 36.57, 74.01, or 91.06 %, respectively. T/P in submaximal concentrations produced 26 % vs 16% when added separately. This character was not seen when T or P was combined with M.
Conclusion: Combination calcium channel blockers as P with sodium channel blockers such as T but not with opioid agonists seems to be a promising therapy for NP.
Funding: The work was supported by the 2018-1.3.1-VKE-2018-00030 project