Danggui-Shaoyao-San (DSS) is a traditional Chinese medicine, which has long been used for pain treatment and has been demonstrated to possess anti-oxidative, cognitive enhancement, and anti-depressant effects. In the present study, the effects of aqueous extracts of DSS on spontaneous pain behaviors and long-term hyperalgesia were examined to investigate the anti-nociceptive effects and underlying mechanisms. Single pretreatment of DSS dose-dependently reduced spontaneous flinches/licking time in the second, rather than the first, phase after subcutaneous injection of 5 % formalin into one hindpaw, in doses of 2.4 and 9.6 g/kg. DSS also dose-dependently inhibited FOS and cyclooxygenase-2 (COX-2) expression in both superficial and deep layers within the spinal dorsal horn. Further, DSS reduced hypoalgesia in the injected paw from 1 to 3 days and produced anti-hyperalgesic actions in both the injected paw after 3 days and non-injected paw. These data suggest involvement of enhancement of descending pain inhibition by suppression of 5-HTT levels in the spinal dorsal horn and reduction of peripheral long-term inflammation, including paw edema and ulcers. These findings suggest that DSS may be a useful therapeutic agent for short- and long-term inflammation induced pain, through both anti-inflammatory and suppression of central sensitization mechanisms.
Keywords: Anti-nociception; Cyclooxygenase-2 (COX-2); Danggui-Shaoyao-San (DSS); FOS; Formalin test; Hyperalgesia; Inflammation; Serotonin transporter (5-HTT).