Antinociceptive effects of intragastric dl-tetrahydropalmatine on visceral and somatic persistent nociception and pain hypersensitivity in rats

Although tetrahydropalmatine (THP), an alkaloid constituent of plants from the genera Stephania and Corydalis, is known to have analgesic property, the antinociceptive effects of THP have not been well evaluated experimentally and the appropriate indications for treatment of clinical pain remain unclear. In the present study, nociceptive and inflammatory models of both somatic and visceral origins were used to assess the antinociceptive and antihyperalgesic effects of intragastric (i.g.) pretreatment of dl-THP in rats. In the bee venom (BV) test that has been well established experimentally, i.g. pretreatment of three doses of dl-THP (20, 40, 60 mg/kg, body weight) resulted in less stably antinociceptive effect on the BV-induced persistent paw flinches that are known to be processed by spinal nociceptive circuit, however the drug of the two higher doses produced distinct suppression of the BV-induced persistent nociception rated by nociceptive score that reflects both spinal and supraspinal mediation. Similarly, the antinociception of dl-THP (60 mg/kg) was only significant for phase 1 but not for phase 2 of the formalin-induced persistent paw flinches, however, the inhibition was distinct for both phase 1 and phase 2 of the formalin nociceptive score. For the antihyperalgesic effect, in contrast, pretreatment of dl-THP (60 mg/kg) produced significant inhibition of both primary hyperalgesia to either thermal or mechanical stimuli and the mirror-image thermal hyperalgesia identified in the By test. In the acetic acid writhing test, the number of writhes was completely blocked at the first 5-min interval followed by a sustained suppression in the remaining period of the whole time course comparing to the vehicle control. These data suggest that i.g. pre-administration of dl-THP could more effectively inhibit visceral nociception as well as thermal and mechanical inflammatory pain hypersensitivity (hyperalgesia) than persistent nociception. Moreover, the drug is likely to produce more effectiveness on supraspinally processed nociceptive behaviors than spinally mediated nociceptive behaviors, implicating an action of THP at the supraspinal level. (C) 2011 Elsevier Inc. All rights reserved.