Studies on a novel regimen for management of orofacial pain and morphine tolerance

Background/purpose: The prevalence of orofacial pain is high but the etiology of orofacial pain is not well understood. Because of clinical treatment is not so effective, it is urgent to explore novel regimens with more effective and less side effects for clinical application. Materials and methods: Male mice (ICR strain) were injected with capsaicin (10μg/5 μl) in vibrissa pad. Spontaneous orofacial pain in 20 min was recorded after receiving capsaicin to quantify the nociceptive level. Green tea polyphenols (GTP 60 mg/kg), memantine (Mem 10 mg/kg), and GTPm (GTP 30 mg/kg plus Mem 3 mg/kg) were dissolved in 2% carboxymethyl cellulose, which was orally administered to mice twice per day and five times per week consecutively for 2 weeks. TruScan photobeam tracking was used to record changes of behavior and locomotor activities. Results: GTPm by itself attenuated orofacial pain induced by capsaicin. Moreover, GTPm enhanced morphine analgesic effects, reduced morphine depressant side effects and delayed morphine tolerance. Along with this experiment, GTPm was tested on the hot plate (52 °C)-induced peripheral thermal pain. It was found that both memantine and GTPm reduced morphine-analgesia in hind paw thermal pain. Conclusion: In this study, GTP (60 mg/kg/day) orally administrated produced a significant analgesic effect on capsaicin–induced orofacial pain. Memantine combined with GTP synergistically not only reduced orofacial pain but also enhanced morphine analgesic effects. Thus, a new regimen of GTPm orally administered twice per day attenuated orofacial pain after consecutive 5 days.