Selective for COX-2 over COX-1, compound 10 exhibited IC<sub>50</sub> 0.02 µM for COX-2 and reversed acetic acid induced inflammation in rats by 73% when used at 10 mg kg<sup>-1</sup> dose and the same dose of the compound also rescued the animals from inflammatory phase of formalin induced hyperalgesia.
The prevention of this hyperalgesia by diclofenac (1-10μg), the inhibitors of COX-1 SC-560 (0.1-1μg) or COX-2 celecoxib (1-5μg), the TRPV1 antagonist capsazepine (0.03-0.3μg) or the TRPA1 antagonist HC030031 (10-50μg) demonstrates the involvement of prostaglandin synthesis and TRP sensitization in CCL5-evoked hyperalgesia.
The results of the study suggest participation of COX-1, COX-2 and iNOS, but not nNOS, in transmission of pain stimuli in STZ-induced diabetic hyperalgesia.
Spinal prostaglandins facilitate exaggerated A- and C-fiber-mediated reflex responses and are critical to the development of allodynia early after L5-L6 spinal nerve ligation.