Evaluation of the analgesic and anti-inflammatory effects of possible molecules increasing the effect of carbamazepine in trigeminal neuralgia in rats: Verapamil, ziconotide and silica

Trigeminal neuralgia (TN) is a rare pain syndrome that immensely affects patients' life quality. Nowadays, Carbamazepine is prescribed clinically for symptomatic treatment, but patients cannot tolerate it for long periods due to the side effects. Therefore, we aimed to increase the tolerability or effectiveness of Carbamazepine in combination with other drugs. Rats are randomly divided into six groups (n=30): Sham, CCI-IoN, Carbamazepine, Verapamil+Carbamazepine, Ziconotide+Carbamazepine, and Aeroperl+Carbamazepine. First, all animals underwent chronic constriction injury of the infraorbital nerve (CCI-IoN) to constitute the animal model of trigeminal neuralgia. Then, the mechanical stimulation test (MST) is carried out as a behavioral test by applying a graded series of von Frey filaments (vFF; 0.02g, 0.16g, 0.4g, 1g, and 2g). Afterwards, interleukin-6, interleukin-1β, TNF-α, and TRPV1 (Transient receptor vanilloid-1) levels in the degenerated trigeminal nerve, trigeminal ganglion and serum were tested by ELISA. Additionally, a histological examination of spinal trigeminal nuclei (SpVn) was evaluated. When the responses of the Carbamazepine, Verapamil+Carbamazepine, or CCI-IoN groups to vFF 0,16g and 0,40g filaments were compared, MST scores of Verapamil+Carbamazepine and Carbamazepine were found to be significantly different from the CCI-IoN group (F=6.763; p<0.011; F=7.860; p<0.023). We found that the interleukin-6, interleukin-1β, TNF-α, and TRPV1 were not significantly changed between the experimental groups. Histological examination revealed no morphological changes between groups in the spinal trigeminal nuclei. These results suggest that verapamil and carbamazepine combination may be a novel treatment approach to treat neuropathic pain in TN.