Pain reports · 2026
Zoledronic acid produces analgesia by inhibiting the transient receptor potential vanilloid 1 (TRPV1) channel.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Carvajal-Zamorano Karina, Amaya-Rodríguez César A, Gómez Del Campo Ana, Palacios-Muñoz Angelina, Ardiles Nicolas M, Ancatén-González Carlos, Meza Rodrigo C, Plaza-Briceño Wladimir, Segura Ignacio, Scala Rosa, Tricarico Domenico, Moya Pablo R, Madrid Rodolfo, Chávez Andrés E, Latorre Ramón, Castillo Karen
Аннотация
INTRODUCTION: The TRPV1 channel is activated by noxious heat and capsaicin and is expressed in primary nociceptive fibers, where it plays a key role in pain perception and inflammation. Although vanilloid compounds can induce topical analgesia, their systemic use is limited by thermoregulatory side effects. Zoledronic acid (ZOL), a bisphosphonate widely used to treat bone disorders and cancer-associated bone loss, has reported analgesic properties, although its effects on TRPV1 remain incompletely understood.
OBJECTIVE: To determine whether ZOL modulates TRPV1 channel function and to elucidate the mechanism underlying its analgesic effects.
METHODS: We combined behavioral assays of thermal nociception in mice and Drosophila melanogaster, Ca2+ imaging in primary dorsal root ganglion neurons, electrophysiological recordings from TRPV1 expressed in Xenopus laevis oocytes, and acute hippocampal slice recordings to assess TRPV1-dependent synaptic plasticity.
RESULTS: Systemic ZOL administration significantly reduced thermal nociceptive behaviors in both models without affecting locomotion or core temperature. In vitro, ZOL decreased capsaicin-evoked Ca2+ responses in dorsal root ganglion neurons and markedly reduced TRPV1-mediated currents in excised membrane patches from oocytes. In hippocampal slices, ZOL prevented TRPV1-dependent synaptic depression without altering basal transmission. Loss of inhibition under asymmetric ionic strength conditions suggests a pore-blocking mechanism.
CONCLUSIONS: Our findings identify a previously unrecognized pore-blocking mechanism by which zoledronic acid inhibits TRPV1 channel activity, providing a mechanistic explanation for its analgesic effects. These results support a potential role for bisphosphonates as scaffolds for the development of novel analgesics and as tools to probe TRPV1-mediated pain pathways.
OBJECTIVE: To determine whether ZOL modulates TRPV1 channel function and to elucidate the mechanism underlying its analgesic effects.
METHODS: We combined behavioral assays of thermal nociception in mice and Drosophila melanogaster, Ca2+ imaging in primary dorsal root ganglion neurons, electrophysiological recordings from TRPV1 expressed in Xenopus laevis oocytes, and acute hippocampal slice recordings to assess TRPV1-dependent synaptic plasticity.
RESULTS: Systemic ZOL administration significantly reduced thermal nociceptive behaviors in both models without affecting locomotion or core temperature. In vitro, ZOL decreased capsaicin-evoked Ca2+ responses in dorsal root ganglion neurons and markedly reduced TRPV1-mediated currents in excised membrane patches from oocytes. In hippocampal slices, ZOL prevented TRPV1-dependent synaptic depression without altering basal transmission. Loss of inhibition under asymmetric ionic strength conditions suggests a pore-blocking mechanism.
CONCLUSIONS: Our findings identify a previously unrecognized pore-blocking mechanism by which zoledronic acid inhibits TRPV1 channel activity, providing a mechanistic explanation for its analgesic effects. These results support a potential role for bisphosphonates as scaffolds for the development of novel analgesics and as tools to probe TRPV1-mediated pain pathways.