Despite the prevalence of opioid misuse, opioids remain the frontline treatment regimen for severe pain. However, opioid safety is hampered by side-effects such as analgesic tolerance, reduced analgesia to neuropathic pain, physical dependence, or reward. These side effects promote development of opioid use disorders and ultimately cause overdose deaths due to opioid-induced respiratory depression. The intertwined nature of signaling via μ-opioid receptors (MOR), the primary target of prescription opioids, with signaling pathways responsible for opioid side-effects presents important challenges. Therefore, a critical objective is to uncouple cellular and molecular mechanisms that selectively modulate analgesia from those that mediate side-effects. One such mechanism could be the transactivation of receptor tyrosine kinases (RTKs) via MOR. Notably, MOR-mediated side-effects can be uncoupled from analgesia signaling via targeting RTK family receptors, highlighting physiological relevance of MOR-RTKs crosstalk. This review focuses on the current state of knowledge surrounding the basic pharmacology of RTKs and bidirectional regulation of MOR signaling, as well as how MOR-RTK signaling may modulate undesirable effects of chronic opioid use, including opioid analgesic tolerance, reduced analgesia to neuropathic pain, physical dependence, and reward. Further research is needed to better understand RTK-MOR transactivation signaling pathways, and to determine if RTKs are a plausible therapeutic target for mitigating opioid side effects.
Reproductive choice and reproductive rights are two of the current buzzwords in discussions on population policy, which in India has until recently been dominated by the compulsions of fertility control. This study by Mukhopadhyay and Savithri claims that poverty and gender discrimination together shape the contours of reproductive behaviour of the majority of Indian women, and that any emphasis on the latter has to be based on an understanding of the complex interlinkages among the major forces that constrain women's reproductive behaviour. It contextualises the notion of reproductive choice under conditions of poverty and gender discrimination by exploring the interlinkages of gender with poverty on the one hand, and the interface of both with women's fertility behaviour and reproductive choice on the other. This analysis is based on data generated from a very detailed household survey in two culturally very distinct Indian contexts.The study provides a glimpse of the complex linkages between reduction in gender inequality and poverty alleviation on the one hand, and reproductive choice matters on the other. It rightly underscores the complexities involved in defining female autonomy and delimiting the parameters of choice, and once again illustrates, with new evidence, that autonomy and choice are meaningless unless contextualised. An accessible and helpful addition to reproductive rights literature.
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