RESUMO
Sexual dimorphism among mammals includes variations in the pain threshold. These differences are influenced by hormonal fluctuations in females during the estrous and menstrual cycles of rodents and humans, respectively. These physiological conditions display various phases, including proestrus and diestrus in rodents and follicular and luteal phases in humans, distinctly characterized by varying estrogen levels. In this study, we evaluated the capsaicin responses in male and female mice at different estrous cycle phases, using two murine acute pain models. Our findings indicate that the capsaicin-induced pain threshold was lower in the proestrus phase than in the other three phases in both pain assays. We also found that male mice exhibited a higher pain threshold than females in the proestrus phase, although it was similar to females in the other cycle phases. We also assessed the mRNA and protein levels of TRPV1 in the dorsal root and trigeminal ganglia of mice. Our results showed higher TRPV1 protein levels during proestrus compared to diestrus and male mice. Unexpectedly, we observed that the diestrus phase was associated with higher TRPV1 mRNA levels than those in both proestrus and male mice. These results underscore the hormonal influence on TRPV1 expression regulation and highlight the role of sex steroids in capsaicin-induced pain.
Assuntos
Capsaicina , Dor , Canais de Cátion TRPV , Animais , Canais de Cátion TRPV/metabolismo , Canais de Cátion TRPV/genética , Capsaicina/farmacologia , Masculino , Feminino , Camundongos , Dor/metabolismo , Dor/genética , Hormônios Esteroides Gonadais/metabolismo , Ciclo Estral/efeitos dos fármacos , Limiar da Dor/efeitos dos fármacos , Gânglios Espinais/metabolismo , Gânglios Espinais/efeitos dos fármacos , Gânglio Trigeminal/metabolismo , Gânglio Trigeminal/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Caracteres Sexuais , RNA Mensageiro/metabolismo , RNA Mensageiro/genéticaRESUMO
The Transient Receptor Vanilloid 1 (TRPV1) or capsaicin receptor is a nonselective cation channel, which is abundantly expressed in nociceptors. This channel is an important transducer of several noxious stimuli, having a pivotal role in pain development. Several TRPV1 studies have focused on understanding its structure and function, as well as on the identification of compounds that regulate its activity. The intracellular roles of these channels have also been explored, highlighting TRPV1's actions in the homeostasis of Ca2+ in organelles such as the mitochondria. These studies have evidenced how the activation of TRPV1 affects mitochondrial functions and how this organelle can regulate TRPV1-mediated nociception. The close relationship between this channel and mitochondria has been determined in neuronal and non-neuronal cells, demonstrating that TRPV1 activation strongly impacts on cell physiology. This review focuses on describing experimental evidence showing that TRPV1 influences mitochondrial function.
Assuntos
Sinalização do Cálcio/genética , Mitocôndrias/genética , Dor/genética , Canais de Cátion TRPV/genética , Animais , Cálcio/metabolismo , Humanos , Mitocôndrias/metabolismo , Nociceptividade/fisiologia , Dor/fisiopatologia , Transdução de Sinais/genéticaRESUMO
Transient receptor potential (TRP) channels are remarkable transmembrane protein complexes that are essential for the physiology of the tissues in which they are expressed. They function as non-selective cation channels allowing for the signal transduction of several chemical, physical and thermal stimuli and modifying cell function. These channels play pivotal roles in the nervous and reproductive systems, kidney, pancreas, lung, bone, intestine, among others. TRP channels are finely modulated by different mechanisms: regulation of their function and/or by control of their expression or cellular/subcellular localization. These mechanisms are subject to being affected by several endogenously-produced compounds, some of which are of a lipidic nature such as steroids. Fascinatingly, steroids and TRP channels closely interplay to modulate several physiological events. Certain TRP channels are affected by the typical genomic long-term effects of steroids but others are also targets for non-genomic actions of some steroids that act as direct ligands of these receptors, as will be reviewed here.
Assuntos
Androgênios/metabolismo , Estrogênios/metabolismo , Canais de Potencial de Receptor Transitório/metabolismo , Animais , Humanos , Canais de Potencial de Receptor Transitório/química , Canais de Potencial de Receptor Transitório/genéticaRESUMO
Lysophosphatidic acid or LPA is a phospholipid which has been extensively linked to the generation and maintenance of pain. Several ion channels have also been shown to participate in this pathological process but the link between LPA and these proteins in pain has just recently gained interest. In this respect, the field has advanced by determining the molecular mechanisms by which LPA promotes changes in the function of some ion channels. While some of the actions of LPA include modulation of signaling pathways associated to its specific receptors, other include a direct interaction with a region in the structure of ion channels to affect their gating properties. Here, we focus on the known effects of LPA on some transient receptor potential, sodium, potassium, and calcium channels. As the field moves forward, mechanisms are unveiled with the hope of understanding the underlying causes of pain in order to target these and control this pathophysiological state.