SPICES AND PAIN: A COMMON WORLD The taste of food is heightened by seasoning, and food prepared with the right mixture of spices is one of the major human pleasures and as such a matter of huge economic dimension. It is therefore no wonder that the trade in spices has been of vast historical importance and a major driving force in the late medieval contacts between the East and West. 1 The chemicals responsible for the gustatory and olfactory pleasures of spices are secondary metabolites elaborated by plants primarily for their defence. 1 By some strange perversion, many humans have learned to enjoy low doses of these toxic chemicals, and in so doing ensure the success and survival of the plants producing spices. 1 What are the mechanisms whereby we sense spices, and what do they have to do with functional disorders of the gastrointestinal (GI) tract? Even one decade ago, nobody could envisage that a large family of closely related ion channels act as molecular sensors for distinct spices, yet also detect other sensory modalities including pain. 2 The pioneer that triggered this avalanche of discoveries was the ‘‘capsaicin receptor’’, now termed TRPV1 which stands for ‘‘transient receptor potential vanilloid 1’’ion channel. Responsible for the piquancy of red pepper (Capsicum spp.), the vanilloid capsaicin in its pure form is one of the most painful chemicals we know. It was the Hungarian pharmacologist Nicolas Jancsó who in the middle of the 20th century first recognised that capsaicin acts specifically on nociceptive afferent neurons. 3 The exploration of this unique pharmacological profile of capsaicin led, in 1997, to the identification of TRPV1 as the molecular sensor of capsaicin, selectively expressed by unmyelinated and some thinly myelinated primary afferent neurons. 4 The capsaicin receptor belongs to the superfamily of transient receptor potential (TRP) ion channels, so named after the role these channels play in Drosophila phototransduction. By now at least 28 different

TRP subunit genes have been identified in mammals, comprising six families. 5 Three subunit families, namely the vanilloid TRPs (TRPVs), the melastatin TRPs (TRPMs) and an ankyrin TRP (TRPA1), are relevant to spice sensing (table 1). 2 The TRP channel subunits are made of six transmembrane domains with a pore between transmembrane domains 5 and 6. 5