In vitro pain model in cell lines expressing human TRPV1

Capsaicin (CAP), has undergone extensive research in recent years due to its potential for pain relief, attributed to triggering the activation of TRPV1 receptors, known to be sensitized in painful conditions. This study aims to investigate CAP role in pain therapy within hTRPV1-expressing cell systems, namely ND7/23-hTRPV1 and CHO-hTRPV1. ND7/23 transfection with hTRPV1 was conducted to generate a neuronal model mirroring dorsal root ganglion neurons physiology, involved in pain transmission. To ascertain its specificity to CAP, calcium imaging (CI) was performed. Additionally, automated patch clamp (aPC) was used to determine CAP half maximal effective concentration, assess differences in CAP sensitivity to TRPV1 among neuronal (ND7/23) and non-neuronal (CHO) precursors expressing hTRPV1, and investigate CAP impact on altering inward and outward ionic currents, and on action potentials (APs). CI confirmed CAP specificity to TRPV1 in ND7/23-hTRPV1 transiently expressed cells. aPC experiments revealed a heightened potency of capsaicin in ND7/23-hTRPV1 cells compared to CHO-hTRPV1. CAP effect in inward and outward ionic currents showed a small reduction in inward currents, along with an increase in outward currents at low capsaicin concentration (1μM), and a reduction of outward currents along with no change in inward currents at high concentration (100μM). Same concentrations of capsaicin revealed alterations in AP shape at low concentration and a complete abolishment of AP at high concentration. These results imply that capsaicin, through TRPV1 activation, has the potential to modulate the initiation and propagation of action potentials, reinforcing its role as a potent therapeutic agent for pain modulation and reduction.