ABSTRACT
Neuropathic pain is a debilitating pathological condition that presents significant therapeutic challenges in clinical practice. Unfortunately, current pharmacological treatments for neuropathic pain lack clinical efficacy and often lead to harmful adverse reactions. As G protein-coupled receptors (GPCRs) are widely distributed throughout the body, including the pain transmission pathway and descending inhibition pathway, the development of novel neuropathic pain treatments based on GPCRs allosteric modulation theory is gaining momentum. Extensive research has shown that allosteric modulators targeting GPCRs on the pain pathway can effectively alleviate symptoms of neuropathic pain while reducing or eliminating adverse effects. This review aims to provide a comprehensive summary of the progress made in GPCRs allosteric modulators in the treatment of neuropathic pain, and discuss the potential benefits and adverse factors of this treatment. We will also concentrate on the development of biased agonists of GPCRs, and based on important examples of biased agonist development in recent years, we will describe universal strategies for designing structure-based biased agonists. It is foreseeable that, with the continuous improvement of GPCRs allosteric modulation and biased agonist theory, effective GPCRs allosteric drugs will eventually be available for the treatment of neuropathic pain with acceptable safety.
ABSTRACT
Objective To investigate the effects of cochlear implantation on residual hearing and to evaluate the potential impact of long -term electrical stimulations on residual hearing .Methods 58 hearing impaired children with cochlear implants were included in this study .All subjects could cooperate with behavioral audiometry .Audio-metric evaluations were carried out pre -implantation and 3 ,12 ,24 months post -implantation respectively .Of 58 subjects ,43 were followed up more than 1 year and 17 were followed up more than 2 years .Results All 58 subjects showed significant differences (P0 .05) at 1 ,2 and 4 kHz .Of 17 subjects followed up more than 2 years ,there were significant differences (P<0 .05) between pre- and various return visits post-implantation .Post-implantation return visits ,there were significant differences between 3 months and 12 , 24 months at 0 .25 and 0 .5 kHz respectively ,not any significant differences on 1 ,2 and 4 kHz .There were no sig-nificant differences on each frequency between 12 months and 24 months post- implantation .Conclusion Residual hearing after cochlear implantation could decrease to some extent for various reasons .There were significant differ-ences between 3 and 12 months post-implantation at 0 .25 and 0 .5 kHz .Not any significant differences were ob-served between 12 months and 24 months post-implantation at each frequency .