Inhibitory effect of Phlai capsules on skin test responses among allergic rhinitis patients:a randomized,three-way crossover study

BACKGROUND： Zingiber cassumunar Roxb., commonly known as Phlai in Thai, has been used as a traditional medicine in Thailand for the treatment of various diseases, including inflammation and chronic airway disease. OBJECTIVE： The purpose of this study was to assess the antihistaminic effect of Phlai on skin testing DESIGN, SETTING, PARTICIPANTS AND INTERVENTION： This was a randomized, open-label, three- way crossover study. Twenty allergic rhinitis （AR） patients were enrolled. In randomized sequence, patients received a single dose of Ph/ai capsules （100 or 200 mg） or Ioratadine （10 mg） with a washout period of 1 week between each treatment. MAIN OUTCOME MEASURES： Skin prick testing for histamine and common aeroallergen （house dust mite） were performed before treatment and after 1,2, 3, 4, 6, 8, 12 and 24 hours of treatment. The main treatment outcomes were the mean wheal and flare responses to the skin prick test after treatment. RESULTS： Both 100 mg and 200 mg Phlai doses suppressed wheal and flare responses to house dust mite allergen, but only 200 mg of Phlai capsules significantly suppressed wheal and flare responses to histamine. Repeated measures analysis of variance showed that Ioratadine caused more wheal and flare suppression than Phial capsules in responses to the histamine skin prick test. However, there were no significant differences among the effects of 100 mg Phlai capsules, 200 mg Phlai capsules and Ioratadine in suppression of wheal and flare induced by the mite skin prick test. Both doses of Phlai were well-tolerated with no adverse events.CONCLUSION： Both 100 mg （compound D 4 mg） when taken as a single therapeutic dose, inhibited AR patients. and 200 mg （compound D 8 mg） Phlai capsules, skin reactivity to histamine and mite skin prick tests in TRIAL REGISTRATION： Thai clinical trial registry （TCTR20160510001）

Effects of histamine on spontaneous neuropathic pain induced by peripheral axotomy

The present study was designed to investigate the effects of histamine on spontaneous neuropathic pain （NP） induced by peripheral axotomy. Rats and mice were subjected to complete transection of the left sciatic and saphenous nerves to induce spontaneous NP （the neuroma model）. Rats were then treated with drugs once daily for 30 days （histidine and Ioratadine, i.p.） or 21 days （histamine, i.c.v.）. Autotomy behavior was scored daily until day 50 postoperation （PO）. On days 14 to 21 PO, some rats in the control group were subjected to singlefiber recording. Autotomy behavior was also monitored daily in histidine decarboxylase （the key enzyme for histamine synthesis） knockout （HDC/） and wildtype mice for 42 days. We found that both histidine （500 mg/kg） （a precursor of histamine that increases histamine levels in the tissues） and histamine （50 pg/5 pL） significantly suppressed autotomy behavior in rats. HDC mice lacking endogenous histamine showed higher levels of autotomy than the wildtype. In addition, the analgesic effect of histidine was not antagonized by Ioratadine （a peripherallyacting H1 receptor antago nist）, while Ioratadine alone significantly suppressed autotomy. Electrophysiological recording showed that ectopic spontaneous discharges from the neuromawere blocked by systemic diphenhydramine （an H receptor antagonist）. Our results suggest that hista mine plays an important role in spontaneous NP. It is likely that histamine in the central nervous system is analgesic, while in the periphery, via H receptors, it is algesic. This study justifies the avoidance of a histaminerich diet and the use of peripherallyacting H receptor antagonists as well as agents that improve histamine action in the central nervous system in pa tients with spontaneous NP.