Proceedings of The Physiological Society

Physiology 2015 (Cardiff, UK) (2015) Proc Physiol Soc 34, PC115

Poster Communications

The effects of acute and chronic riboflavin administration on thermonociception and orofacial pain in naive mice

C. R. Bohotin1, T. Alexa2, A. Dondas2, A. Luca2, R. Iliescu2

1. General and Oro-Maxillo-Facial Pathology, University of Medicine and Pharmacy "Gr.T.Popa" Iasi, Iasi, Romania. 2. Centre for the Study and Therapy of Pain, University of Medicine and Pharmacy "Gr.T.Popa", Iasi, Romania.

There is evidence that riboflavin, also known as vitamin B2 (vitB2) is able to improve clinical outcome and to reduce the frequency of migraine attacks in a subgroup of patient with mitochondrial dysfunction [1]. Purpose: to compare the effect of single versus long-term vitB2 administration on thermonociception and orofacial pain in naive mice. Thermonociception was evaluated by hot plate (HPT) and tail flick (TFT) tests; the orofacial pain (OFP) was assessed by formalin injection into the upper lip (mystacial vibrissae) [2]. Methods: BALB/c mice (n=62) were divided in 2 groups: the acute group (AcG, n=32) received either single-dose vitB2 (50mg/kg b.w. i.p.) or an equivalent volume of saline and the chronic group (ChGr, n=30) received daily doses of vitB2 (50 mg/kg b.w. i.p.) or saline for 30 days. In the AcG, HPT and TFT were performed before (baseline) and after vitB2 (n=8) or saline (n=8) administration over a 4h period (at 30, 60, 120, 180 and 240 minutes); for the OFP, mice were evaluated 1h after vitB2 (n=8) or saline (n=8) administration. In the ChG, thermonociception was evaluated at baseline and thereafter every 2 days over a 30 days period. After 28-th dose, TFT and HPT were recorded in the same manner as in AcG. One hour after the 30-th dose of vitB2 (n=8)/saline (n=8) the orofacial pain was evaluate by the mean of OFT. Cut-off was set at 15 s for HPT and at 12 s for TFF. For the OFP, the results were recorded separately for the 1-st phase (acute pain) and 2-nd phase (persistent pain) and expressed as seconds mice spend grooming, rubbing, and/or scratching the injected area. The vitB2 effect was expressed as maximum possible effect [MPE (%) = (treated -baseline)×100/(cut-off - baseline)]. Results are expressed as mean±S.D.(sec or %). ANOVA test was used for statistical analysis. Results: Single dose vitB2 had an analgesic effect on HPT and on the second phase of the OFP (p=0.02). The analgesic effect started 30 min after administration and persisted throughout the experiment, with a maximum MPE at 4h. In the ChG, after the first week, significant analgesia on TFT (p<0.05) and an analgesic tendency on HPT (MPE=8±23%) was noted. This effect disappeared after the first 10 days; in the last 5 days of the experiment, a significant hyperalgesic reaction was observed on HPT (p><0.05, MPE= -12±32.6%). Chronic administration of vitB2 had no effect on the OFP neither when compared with control, nor when compared with single dose vitB2.> Conclusion: In naïve mice without mitochondrial disturbances, riboflavin administration had different effects: single dose and one week treatment, in concordance with literature data [1,3] had an antinociceptive effect on thermonociception and an analgesic effect on persistent phase of OFP. Prolonged vitB2 administration lead to hyperalgesia and cancelled the single-dose's analgesic effect on the OFT. These data demonstrate that chronic large-dose vitB2 treatment can reverse its analgesic effect and turn it into a hyperalgesic one.

Where applicable, experiments conform with Society ethical requirements