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

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 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 painand 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.

Increased Plasma Levels of Brain Derived Neurotrophic Factor (BDNF) in Patients with Fibromyalgia

“…Their results also indicated a significant negative correlation between HAM-D scores and serum BDNF levels. Low expression of BDNF levels are observed in cellular and molecular processes contributing to the development of chronic depression and in animals subjected to stress [23,24]. Thus, it is interesting to note that the levels of BDNF in our patients with FM were increased despite the high level of depressive symptoms.…”

Roles of the hippocampal formation in pain information processing

“…Implicit within these observations is the hypothesis that chronic pain may regulate the expression of NK-1 receptor and BDNF in the hippocampus in a manner similar to that exerted by stress. To address this issue, McCarson's lab has conducted lots of work by using multiple approaches, such as solution hybridization-nuclease protection assays [24,25,195] , and in-situ hybridization [196] . One of the major insights that emerge from these studies is that both NK-1 receptor and BDNF mRNA levels are significantly attenuated by acute (formalin injection) or chronic pain (CFA injection), in accordance with the results initiated by acute or chronic restraint stress.…”

“…It has been generally believed that pain is characterized as a complex experience, dependent not only on the regulation of nociceptive sensory systems, but also on the activation of mechanisms that control mood-affect and emotioncognition in higher brain centers [1,2,25,72,195,196,221] . The emergence of imaging approaches such as positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) allows functional mapping of the intact brain and measurement of the responses in multiple areas simultaneously, thus bringing the study of pain into a deep level [13] .…”

BDNF Overexpression Exhibited Bilateral Effect on Neural Behavior in SCT Mice Associated with AKT Signal Pathway

“…Sun [13] found that nerve growth factor (NGF), BDNF and phosphatidylinositol 3-kinase (PI3K) signal were involving in inflammatory hyperalgesia. Duric et al [14] revealed that the chronic pain evoked up-regulation of neurokinin (NK)-1 receptor and BDNF gene expression in the spinal cord.…”