Protopanaxadiol alleviates neuropathic pain by spinal microglial dynorphin A expression following glucocorticoid receptor activation

Background and Purpose New remedies are required for the treatment of neuropathic pain due to insufficient efficacy available therapies. This study provides a novel approach develop painkillers chronic treatment. Experimental Approach The rat formalin test spinal nerve ligation model were used evaluate antinociception protopanaxadiol. Primary cell cultures, immunofluorescence staining, gene protein expression also performed mechanism studies. Key Results Gavage protopanaxadiol remarkably produces antihypersensitive effects in pain, bone cancer inflammatory with comparable gabapentin. Long-term PPD administration does not induce tolerance, but prevents reverses development morphine analgesic tolerance. Oral specifically stimulates dynorphin A microglia astrocytes or neurons. Protopanaxadiol gavage-related antihypersensitivity is abolished by intrathecal pretreatment microglial metabolic inhibitor minocycline, antiserum specific κ-opioid receptor antagonist GNTI. Intrathecal glucocorticoid receptor)antagonists RU486 dexamethasone-21-mesylate, GPR-30 G15 mineralocorticoid eplerenone, completely attenuates protopanaxadiol-induced pain. Treatment protopanaxadiol, agonist dexamethasone membrane-impermeable dexamethasone-BSA cultured induces remarkable expression, which totally blocked dexamthasone-21-mesylate. Conclusion Implications All results, first time, indicate that probably through after activation hypothesize membrane receptor/dynorphin pathway potential target discover