Hypericum perforatum L. as adjuvant of opioid analgesia in an animal model of migraine

Aims: Despite their high analgesic efficacy, opioids can provide only partial pain relief during a migraine attack and their tolerability profile is unsatisfactory. The aim of the present study was to investigate the potentiating properties of Hypericum perforatum L. (SJW) to identify a safe and tolerable adjuvant to opioid analgesia in migraine therapy. Study Design: Experimental study. Place and Duration of Study: Department of Neuroscience, Psychology, Drug Research, and Child Health (NEUROFARBA), University of Florence, Florence, Italy, between September 2008 and July 2009. Methodology: A mouse model of meningeal nociception induced by administration of the nitric oxide donor sodium nitroprusside (SNP) was used. The following treatment groups were used: saline, SNP, morphine, SJW, SNP+morphine, SNP+SJW, SNP+morphine+SJW. The presence of thermal allodynia was evaluated through the cold plate test. The presence of behavioural side effects was determined by the evaluation of locomotor activity (rotarod test), spontaneous mobility and inspection activity (hole board test). Results: SNP induced a long lasting thermal allodynia that appeared after 1 h, peaked after 3-4 h and disappeared 6 h after administration. The co-injection of a single low dose of SJW (1 mg/kg) with morphine (2-5 mg/kg) greatly increased the opioid analgesia (P<.05). SJW, when administered alone,was unable to counteract SNP-induced allodynia. Among the main components of this herbal drug, hypericin produced a potentiating activity comparable to that induced by SJW whereas hyperforin and flavonoids were ineffective. Animal gross’ behavior and locomotor activity were not altered by co-administration of morphine and SJW. Conclusion: Present results showed the potentiating activity of SJW on morphine antinociception in an animal model of migraine. This herbal drug might be proposed as adjuvant to opioid agonists to produce analgesia using lower, safer doses of opioids. This combination might represent a therapeutic perspective for migraine pain.