In an important study published in 2010, Miller et al. showed that the duration of muscle cramping was reduced by administration of oral pickle juice immediately following electrically induced muscle cramps in hypohydrated humans. The authors concluded that this effect could not be explained by rapid restoration of body fluids or electrolytes and suggested that it reflected a neutrally mediated reflex originating in the oropharyngeal region and inhibiting the firing of α motor neurons of the cramping muscle. This observation led to the hypothesis that the mechanism by which pickle juice attenuated exercise-induced muscle cramping (EAMC) may involve stimulation of transient receptor potential (TRP) channels. These TRP channels have been found in the upper gastrointestinal tract (GIT), including the oropharyngeal region. Here we explore some of the methodological considerations related to a novel approach to study EAMC in the laboratory, EAMC as a more complex clinical entity than previously considered, and the complexity of TRP channels and their possible role in EAMC.