Title

 

Authors

R. Russo¹, G. D’Agostino¹, A. Iacono¹, G. Mattace Raso¹, R. Meli¹,  R. Berni Canani², and A. Calignano¹.

¹Dipartimento di Farmacologia Sperimentale, ²Dipartimento di Pediatria, Università degli Studi di Napoli “Federico II”; Napoli.

 

Abstract

Short chain fatty acids (SCFAs) are derived from microbial fermentation of undigested dietary fibres in the colon (1). The amount of SCFAs (mainly acetate, propionate and butyrate) are produced in the colon and butyrate is known to modulate numerous processes (2). Previously, positive effects of butyrate on inflammation in active distal ulcerative colitis have been reported as well as the ameliorative effects on several inflammatory parameters such as cytokine production and myeloperoxidase activity, primarily via inhibition of nuclear factor kappa B activation (3,4). We have tested the effects of a synthetic butyrate derivative able to release butyrate at intestinal level in comparison to equimolecular  doses of sodium butyrate in two models of acute (formalin-induced paw licking in mice) and visceral pain( acetic acid-induced writhing in mice) Sodium butyrate (10-100 mg/kg) and of N-(1-carbamoyl-2-phenyl-ethyl) butyramide (21,2-212 mg/kg) (BuToRo) have been  orally administered 30 min before formalin or acetic acid  injection. Acute administration of sodium butyrate or BuToRo at all the doses tested, were ineffective in reducing pain both in acute or visceral models. Repeated  treatments (once a day for three days) of BuToRo, but not of sodium butyrate, resulted active in reducing the first phase (48% inhibition vs control p<0.01 n=12) of paw licking whereas was ineffective in reducing the second phase. In the model of visceral pain both drugs resulted active in reducing acetic acid-induced writhing although BuToRo resulted much active than sodium butyrate.( 33% vs 68% respectively p<0.01 n=12). We conclude that butyrate is involved in pain signalling. In particularly single administration are non effective in both pain models, whereas the increase of plasmatic levels of butyrate due to repeated treatment, results in an analgesic effect on acute phase of formalin and acetic acid-induced visceral pain. Surprisingly both drugs were ineffective in reducing the inflammatory phase of formalin although previous results indicate an anti-inflammatory effect of butyrate. Our results strongly suggest the involvement of butyrate in the control of acute sensorial pain initiation whereas the inflammatory pain seems to be not controlled by butyrate levels. Further studies will need to better understand this peculiar effect.
 
 
References

1.      DL Topping et al., Physiol Rev (2001); 81:1031-1064
2.      S Macfarlane et al., Proc Nutr Soc (2003); 62:67-72
3.      HM Hamer et al., Clin. Nut. (2010) 29(6):738-44.
4.      JP Segain et al., Gut. (2000);47(3):397-403