Augmentation of analgesic effects following co-administration of vanilloid receptor blocker and cyclooxygenase type 2 inhibitor in rat formalin test

The transient receptor potential cation channel subfamily V member 1 (TRPV1) receptors play a substantial role in pain transmission and the receptor antagonist capsazepine could alleviate pain in various pharmacological models. On the other hand, the enzyme cyclooxygenase type 2 (COX-2) has been shown to exist in central nervous system, particularly in hippocampal glutamatergic neurons as well as in cortex and the enzyme inhibition could alleviate pain transmission and perception. The aim of the present study was to investigate the analgesic effect of capsazepine and its possible interaction with COX-2 inhibition in the brain.

Male wistar rats (200–250 g) were used in this study. One week after insertion of a stainless steel guide cannula by stereotaxic surgery, drugs were administered into left lateral ventricle on the day of experiment 10 min before formalin test and the pain related behavior of the rat was measured based on method described by Dubuisson and Dennis. Experimental groups consisted of capsazepine (5 and 50 nM), celecoxib (2 and 20 nM), and co-administration of capsazepine (5 nM) and celecoxib (2 nM).

Results showed a significant decrease in pain related behavior in rats received capsazepine 5 nM (92.4 ± 1.1), capsazepine 50 nM (57.0 ± 2.1), celecoxib 2 nM (83.9 ± 1.1), or celecoxib 20 nM (51.6 ± 1.4) compared with the control (103.60 ± 2.0) group. Moreover, co-administration of celecoxib (2 nM) and capsazepine (5 nM) significantly decreased pain related behavior of rats (50.6 ± 0.8) compared with the group received celecoxib (2 nM) or capsazepine (5 nM) alone, respectively.

The results suggest a possible additive and/or synergistic interaction between celecoxib and capsazepine in analgesic effects in formalin test.