Effects of intrathecal BAM22 on noxious stimulus-evoked c- fos expression in the rat spinal dorsal horn

Abstract

The effects of bovine adrenal medulla 22 (BAM22), a cleaved product of proenkephalin A, were investigated on the noxious stimulus-evoked expressions of spinal c- fos-like immunoreactivity (FLI). Heat (51 °C) applied to the tail evoked FLI predominantly in laminae I–II of the sacral spinal cord. Intrathecal (i.t.) BAM22 at a dose of 7 nmol decreased the expressions of the heat-evoked FLI by 68%, 64% and 56% in laminae I–II, III–IV and V–VI, respectively, and the decrease pattern was comparable to that induced by i.t. morphine (10 μg). Naloxone (1 mg/kg, i.p.) significantly enhanced the heat-evoked FLI in laminae III–VI, prevented the morphine-induced inhibition, and decreased the potencies of BAM22 in laminae I–II and V–VI by 23–40%. Higher dose of naloxone (10 mg/kg, i.p.) also partially reduced the BAM22-induced suppression. Following intraplantar injection of formalin (2.5%), FLI neurons were preferentially distributed not only in laminae I–II but also in laminae III–IV and V–VI of segments L4–L5. Pretreatment with BAM22 (7 nmol, i.t.) reduced the formalin-evoked FLI neurons by 72%, 61% and 58%, in laminae I–II, III–IV and V–VI, respectively. Naloxone (1 mg/kg. i.p.) enhanced the formalin-evoked expressions of FLI in laminae III–VI and decreased the potencies of BAM22 by 22–38% in laminae I–II and V–VI. The present study provided evidence at a cellular level showing that opioid and non-opioid effects of BAM22 on nociceptive processing in acute and persistent pain models were associated with modulation of noxious stimulus-evoked activity of the spinal dorsal horn neurons.