<p>The TRPV1 ion channel and the NMDA receptor represent promising targets for the development of new analgesics. This study assessed the effects of the TRPV1 agonist capsaicin, the TRPV1 antagonist 4‑(3-chloro-2-pyridinyl)-N-4-(1,1-dimethylethyl)phenyl-1-piperazinecarboxamide (BCTC) and the NMDA receptor blocker N-(2-adamantyl)-hexamethyleneimine hydrochloride (hemantane) on pain response controlled by spinal and supraspinal structures of the central nervous system in C57Bl/6 mice. The threshold in the tail flick test was investigated as a pain response controlled by spinal and supraspinal structures of the central nervous system. Licking of the hind paws and jumping response to skin contact with a heated metal surface in the hot plate test were used as behavioral reactions controlled by the brain. In the tail flick test in mice, BCTC (20 mg/kg intraperitoneally) and hemantane (40 mg/kg intraperitoneally) significantly increased the tail flick threshold by 43 and 25%, respectively. Capsaicin (1 mg/kg, subcutaneously) significantly increased the tail flick threshold up to the cut-off time (maximum stimulus time). BCTC decreased the effect of capsaicin by 2.8 times; in this group of animals, no significant change in the tail flick threshold was recorded compared to the control group of mice that were administered solvents. Hemantane decreased the effect of capsaicin by 1.8 times, while the tail flick threshold in this group was significantly 64% higher than in the control group. In the hot plate test, capsaicin, BCTC and hemantane did not have a significant effect on the jumping and hind paw licking latencies. However, hemantane in combination with capsaicin increased the threshold of hind paw licking by 55.5% compared to the control group. Thus, the NMDA receptor blocker hemantane in combination with capsaicin decreases the threshold in the tail flick test and increases the threshold in the hot plate test.</p>