PMID- 16956981 OWN - NLM STAT- MEDLINE DCOM- 20070109 LR - 20131121 IS - 0022-3565 (Print) IS - 0022-3565 (Linking) VI - 319 IP - 3 DP - 2006 Dec TI - Effects of analgesic or antidepressant drugs on pain- or stress-evoked hippocampal and spinal neurokinin-1 receptor and brain-derived neurotrophic factor gene expression in the rat. PG - 1235-43 AB - 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 nonsteroidal anti-inflammatory drug and a tricyclic antidepressant 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 complete Freund's adjuvant 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 neurokinin (NK)-1 receptor and brain-derived neurotrophic factor (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 although analgesic drug treatment reduces nociceptive sensory activation in the spinal cord, it is insufficient to prevent the impact of pain on the hippocampus. Conversely, although 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 central nervous system. FAU - Duric, Vanja AU - Duric V AD - Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, 3901 Rainbow Blvd., MSN 1018, Kansas City, KS 66160, USA. FAU - McCarson, Kenneth E AU - McCarson KE LA - eng GR - DA12505/DA/NIDA NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20060906 PL - United States TA - J Pharmacol Exp Ther JT - The Journal of pharmacology and experimental therapeutics JID - 0376362 RN - 0 (Analgesics) RN - 0 (Anti-Inflammatory Agents, Non-Steroidal) RN - 0 (Antidepressive Agents) RN - 0 (Antidepressive Agents, Tricyclic) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Receptors, Neurokinin-1) RN - 9007-81-2 (Freund's Adjuvant) RN - OGG85SX4E4 (Imipramine) RN - XXE1CET956 (Indomethacin) SB - IM MH - Analgesics/*pharmacology MH - Animals MH - Anti-Inflammatory Agents, Non-Steroidal/pharmacology MH - Antidepressive Agents/*pharmacology MH - Antidepressive Agents, Tricyclic/pharmacology MH - Behavior, Animal/drug effects MH - Brain-Derived Neurotrophic Factor/*biosynthesis/genetics MH - Foot MH - Freund's Adjuvant MH - Gene Expression/drug effects MH - Hippocampus/drug effects/*metabolism MH - Imipramine/pharmacology MH - In Situ Hybridization MH - Indomethacin/pharmacology MH - Injections MH - Male MH - Nuclease Protection Assays MH - Pain/chemically induced/*physiopathology MH - Physical Stimulation MH - Rats MH - Rats, Sprague-Dawley MH - Receptors, Neurokinin-1/*biosynthesis MH - Spinal Cord/drug effects/*metabolism MH - Stress, Psychological/*physiopathology EDAT- 2006/09/08 09:00 MHDA- 2007/01/11 09:00 CRDT- 2006/09/08 09:00 PHST- 2006/09/08 09:00 [pubmed] PHST- 2007/01/11 09:00 [medline] PHST- 2006/09/08 09:00 [entrez] AID - jpet.106.109470 [pii] AID - 10.1124/jpet.106.109470 [doi] PST - ppublish SO - J Pharmacol Exp Ther. 2006 Dec;319(3):1235-43. doi: 10.1124/jpet.106.109470. Epub 2006 Sep 6.