Received for publication June 16, 2006.
Revised August 9, 2006.
Accepted for publication August 31, 2006.

Effects of analgesic or antidepressant drugs on pain- or stress-evoked hippocampal and spinal neurokinin-1 (NK-1) receptor and brain-derived neurotrophic factor (BDNF) gene expression in the rat

Abstract

Clinical studies show that people suffering from chronic pain are often also burdened by depression. Antidepressants are used to treat some types of chronic pain; however, little is known about their mechanisms of action. This study addressed the effects of a non-steroidal anti-inflammatory (NSAID) and a tricyclic antidepressant (TCA) drug on pain- and stress-evoked gene expression in the rat spinal cord dorsal horn and hippocampus. Rats were pretreated with either indomethacin or imipramine and then challenged with either intraplantar CFA or a bout of immobilization stress. Results showed that indomethacin significantly reduced nociception-related peripheral edema, hyperalgesia, and reversed the pain-evoked up-regulation of NK-1 receptor and BDNF gene expression in the spinal cord to levels not statistically different from controls. However, indomethacin did not protect against significant pain-induced down-regulation of these genes in the hippocampus by approximately 50%, suggesting that while analgesic drug treatment reduces nociceptive sensory activation in the spinal cord, it is insufficient to prevent the impact of pain on the hippocampus. Conversely, while imipramine did not provide significant behavioral analgesia, it significantly blocked both pain- and stress-evoked alterations in hippocampal and spinal NK-1 and BDNF gene expression. Thus, these results show that application of either analgesic or antidepressant drugs alone does not fully protect against both the behavioral and molecular effects of persistent pain on both "sensory" and "affective" processing within the CNS.

Key words: affect, dorsal horn, imipramine, immobilization, indomethacin, inflammation