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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Section of Pharmacology and Toxicology, Department of Neurosciences, Psychology, Drug Research and Child Health (NEUROFARBA), University of Florence, Florence, Italy.
Maria Domenica
MD
Sanna
Section of Pharmacology and Toxicology, Department of Neurosciences, Psychology, Drug Research and Child Health (NEUROFARBA), University of Florence, Florence, Italy.
Carla
C
Ghelardini
Section of Pharmacology and Toxicology, Department of Neurosciences, Psychology, Drug Research and Child Health (NEUROFARBA), University of Florence, Florence, Italy.
Nicoletta
N
Galeotti
D000818:Animals; D004195:Disease Models, Animal; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D020902:Hypericum; D008297:Male; D051379:Mice; D009020:Morphine / Q000008:administration & dosage*; D009437:Neuralgia / Q000188:drug therapy* / Q000503:physiopathology; D010147:Pain Measurement / Q000187:drug effects* / Q000379:methods; D010936:Plant Extracts / Q000008:administration & dosage*; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D016896:Treatment Outcome
D010936:Plant Extracts; D009020:Morphine
Hypericin; Neuropathic Pain; PKCγ; St. John’s Wort;  Morphine