Abstract
Chronic pain frequently leads to anxiety, depression and microglia-related inflammation is the common mechanism for chronic pain and psychiatric disorders. Activation of alpha 7 nicotinic acetylcholine (α7 nAch) receptor suppresses microglia-related inflammation. Thus, we evaluated the activation of α7 nAch receptors on chronic pain-induced anxiety- and depression-like behaviors and explored the potential mechanisms. Open field, sucrose preference, and pain behavior tests (paw withdrawal threshold, and cold response to acetone) were evaluated in male Wistar rats that received spared nerve injury (SNI) and complete Freund’s adjuvant (CFA) into the unilateral ankle articular cavity. The effect of intracerebroventricular (ICV) injection of α7 nAch receptor agonist PHA and α7 nAch receptor antagonist on anxiety and depression-like behaviors and cytokines expression were examined. Cytokines in medial prefrontal cortex (mPFC), basolateral amygdala (BA), and ventral hippocampus (VH) were measured using enzyme-linked immune absorbent assay. SNI surgery and CFA injection induced anxiety- and depression-like behaviors, and ICV injection of PHA reduced that anxiety- and depression-like behaviors. SNI surgery and CFA injection skewed the mPFC, BA, and VH to a pro-inflammatory response and ICV injection of PHA shift brain to an anti-inflammatory response in those sites. The anti-depressive effect and anti-inflammatory effect of PHA were reversed by WNT/β-catenin inhibitor. Activation of alpha7 nicotinic acetylcholine receptors reduces chronic pain-induced anxiety- and depression-like behaviors, the mechanisms may be attributed to the activation of WNT/β-catenin pathway and suppression of brain inflammation.
Daikenchuto, a traditional Japanese herbal medicine, ameliorates postoperative ileus by anti-inflammatory action through nicotinic acetylcholine receptors
