St. John’s Wort Potentiates anti-Nociceptive Effects of Morphine in Mice Models of Neuropathic Pain

Abstract

In this study, we compared the efficacy of a combination of PKC-blocker St. John's Wort (SJW) and morphine in mice with painful antiretroviral (2,3-dideoxycitidine [ddC]) and chemotherapic (oxaliplatin) neuropathy. Morphine (1 and 5 mg/Kg i.p.), SJW (1 and 5 mg/Kg o.s.), or their combination was administered by systemic injection, and antinociception was determined by using the hot and cold plate tests. Here we demonstrate the ability of SJW to relieve neuropathic pain in mice neuropathic models and a potentiation of morphine antinociception in thermal pain. The potentiating effect shown by SJW was not secondary to its antinociceptive activity as the increase of the morphine antinociceptive effect was produced at a dose (1mg/kg o.s.) devoid of any capability to modulate the pain threshold in neuropathic pain mice. Further examinations of the SJW main components revealed that hypericin was responsible for the potentiating properties whereas flavonoids were ineffective. These results show that SJW has notable antinociceptive activity for both neuropathic pain models and could be used in neuropathic pain relief alone or in combination with morphine. These data support the utility of combination SJW/opioid therapy in pain management for antinociceptive efficacy by enhancing opioid analgesia.