targeting trpv1 for inflammatory pain relief: a review of quinoline derivatives as potential inhibitors and their mechanisms from molecular docking to in vivo validation

The transient receptor potential vanilloid 1 (trpv1) channel plays a crucial role in the body’s perception of pain, responding to a variety of stimuli including noxious heat, acidity, and specific chemicals. it is particularly involved in inflammatory pain pathways, with its activity influenced by factors like posttranslational modifications and inflammatory molecules. trpv1 is activated by temperatures above 43°c, which are typically considered harmful or noxious, acidic conditions, and chemical agents such as capsaicin—the compound responsible for the spiciness of chili peppers—and naturally occurring vanilloids in the body. structurally, trpv1 is a tetramer with specialized cytoplasmic domains that regulate its sensitivity and function. during inflammation, the channel becomes more sensitive due to interactions with molecules like prostaglandins and bradykinin, which contribute to heightened pain perception (hyperalgesia). while sustained activation of trpv1 can lead to desensitization through mechanisms such as phosphorylation and receptor internalization, this property also presents opportunities for therapeutic interventions. efforts to develop trpv1 antagonists for pain relief have shown promise, though their clinical use has been limited by side effects, particularly hyperthermia. however, this issue is generally associated with global trpv1 antagonism, and more targeted approaches—such as peripheral or central inhibition—may offer a safer therapeutic profile. recent research has focused on strategies that target trpv1 subunit interactions rather than directly blocking the channel, offering the potential for more effective and safer treatments. this review explores the molecular mechanisms of trpv1 activation, its role in inflammation-induced pain, and the emerging therapeutic potential of quinoline-based compounds, integrating insights from molecular docking studies, pharmacokinetic evaluations, and in vivo experiments.