Antinociceptive effects of imidazoline I2 receptor agonists in the formalin test in rats (658.2)

Abstract

Pain is a significant global public health problem and currently available analgesics are not adequate to meet the clinical needs, leaving a big population with undertreated pain. The imidazoline I2 receptor is an emerging drug target for analgesics as I2 receptor agonists demonstrate antinociceptive effects in rodent models of acute and chronic pain. However, little is known of the neuroanatomical mechanism mediating I2 receptor agonist‐induced antinociception. This study examined the effects of the selective I2 receptor agonists 2‐BFI, BU224, and CR4056 using the formalin test in rats. 2‐BFI (1‐10 mg/kg, i.p.) and BU224 (1‐10 mg/kg, i.p.) dose‐dependently attenuated the spontaneous flinching behavior observed during 10min (phase 1) and 20‐60min (phase 2) following formalin (2%, 50µl) treatment, while CR4056 (1‐32 mg/kg, i.p.) only decreased phase 2 flinching. Local administration of 2‐BFI (1‐10 mg/kg, s.c.) to the hindpaw of rats had no antinociceptive effects. In contrast, centrally delivered 2‐BFI (10‐100 µg, i.c.v.) dose‐dependently attenuated phase 1 and phase 2 flinching. Together, these data suggest that I2 receptor agonists produce significant antinociception via a central mechanism and further supports that I2 receptors may represent a novel drug target to treat pain. (DA034806)Grant Funding Source: Supported by R01 DA034806/DA/NIDA NIH HHS/United States