Reduced aversion to oral capsaicin following neurotoxic destruction of superficial medullary neurons expressing NK-1 receptors

Aversion to capsaicin (0.1–10 ppm) was assessed using a two-bottle paired preference paradigm, before and after intracisternal injection of substance P conjugated to saporin (SP-SAP) to ablate neurons in superficial medullary and cervical dorsal horn that express NK-1 receptors. Before SP-SAP, there was a concentration-dependent decrease in consumption of capsaicin with a threshold of 0.1–0.3 ppm. Following SP-SAP, significantly more capsaicin solution was consumed at 1- and 10-ppm concentrations. These results support a role for substance P in the mediation of high, but not low, levels of capsaicin-induced oral irritation.