Rat Trigeminal Ganglion Neuron Responses to Piperine in a Low-pH Environment, and Capsazepine-Induced Block

ABSTRACT

This study examined the responses of cultured adult rat trigeminal ganglion neurons to protons and to capsazepine and piperine, two substances known to produce pain and hyperalgesia in humans. Whole-cell patch clamp recordings were performed on cultured adult rat trigeminal ganglion(TG) neurons voltage-clamped near their resting membrane potential(-60mV). Piperine(10nM) caused a sustained inward current associated with either an increase or decrease in membrane conductance. When protons and piperine were coapplied, the membrane currents evoked in piperine-sensitive TG neurons far exceeded the algebraic sum of the responses to the two stimuli applied in isolation. Capsazepine blocked the response of TG neurons to piperine at both physiological and acidic pH. In the presence of capsazepine, responses to the mixture of piperine and protons resembled the response to a low pH stimulus applied alone. Capsazepine had no effect on sustained proton-induced current. These findings suggest that protons enhance piperine current by altering the vanilloid receptor/channel complex or by increasing the length constant of the space clamp. This study reveals that cultured trigeminal ganglion neurons show features of chemonociceptors and may provide a useful model for studying the mechanism of chemical pain production.