{"title":"纳洛酮可以限制吗啡过敏:考虑分子机制","authors":"Mojgan Baratzadeh , Samira Danialy , Shima Abtin , Homa Manaheji","doi":"10.1016/j.npep.2023.102345","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><p><span><span>Naloxone<span><span> has been used as an opioid antagonist to prevent multiple adverse side effects of opioid-like tolerance and </span>hyperalgesia. This study has investigated naloxone combined with morphine to limit pain </span></span>hypersensitivity. In addition, the expression of brain-derived neurotrophic factor (BDNF) and K</span><sup>+</sup> Cl<sup>−</sup> cotransporter2 (KCC2) were also studied.</p></div><div><h3>Methods</h3><p><span><span>Forty-eight adult male Wistar rats (180–220 g) were divided into eight groups, with six rats in each group. Rats were divided into two tolerance and hyperalgesia groups; the sham group, the morphine group, the treatment group (naloxone along with morphine), and the sham group (naloxone along with saline) for eight consecutive days. Tail-flick test was performed on days 1, 5, and 8, and the plantar test on days 1 and 10. On days 8 and 10, the lumbar segments of the spinal cord were collected, and BDNF and KCC2 expression were analyzed using </span>western blotting and </span>immunohistochemistry, respectively.</p></div><div><h3>Results</h3><p>Results showed that tolerance and hyperalgesia developed following eight days of repeated morphine injection. BDNF expression significantly increased, but KCC2 was downregulated. Co-administration of naloxone and morphine decreased tolerance and hyperalgesia by decreasing BDNF and increasing KCC2 expression, respectively.</p></div><div><h3>Conclusion</h3><p>This study suggests that BDNF and KCC2 may be candidate molecules for decreased morphine tolerance and hyperalgesia.</p></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":null,"pages":null},"PeriodicalIF":2.5000,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Naloxone could limit morphine hypersensitivity: Considering the molecular mechanisms\",\"authors\":\"Mojgan Baratzadeh , Samira Danialy , Shima Abtin , Homa Manaheji\",\"doi\":\"10.1016/j.npep.2023.102345\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><p><span><span>Naloxone<span><span> has been used as an opioid antagonist to prevent multiple adverse side effects of opioid-like tolerance and </span>hyperalgesia. This study has investigated naloxone combined with morphine to limit pain </span></span>hypersensitivity. In addition, the expression of brain-derived neurotrophic factor (BDNF) and K</span><sup>+</sup> Cl<sup>−</sup> cotransporter2 (KCC2) were also studied.</p></div><div><h3>Methods</h3><p><span><span>Forty-eight adult male Wistar rats (180–220 g) were divided into eight groups, with six rats in each group. Rats were divided into two tolerance and hyperalgesia groups; the sham group, the morphine group, the treatment group (naloxone along with morphine), and the sham group (naloxone along with saline) for eight consecutive days. Tail-flick test was performed on days 1, 5, and 8, and the plantar test on days 1 and 10. On days 8 and 10, the lumbar segments of the spinal cord were collected, and BDNF and KCC2 expression were analyzed using </span>western blotting and </span>immunohistochemistry, respectively.</p></div><div><h3>Results</h3><p>Results showed that tolerance and hyperalgesia developed following eight days of repeated morphine injection. BDNF expression significantly increased, but KCC2 was downregulated. Co-administration of naloxone and morphine decreased tolerance and hyperalgesia by decreasing BDNF and increasing KCC2 expression, respectively.</p></div><div><h3>Conclusion</h3><p>This study suggests that BDNF and KCC2 may be candidate molecules for decreased morphine tolerance and hyperalgesia.</p></div>\",\"PeriodicalId\":19254,\"journal\":{\"name\":\"Neuropeptides\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.5000,\"publicationDate\":\"2023-08-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Neuropeptides\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0143417923000264\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"ENDOCRINOLOGY & METABOLISM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neuropeptides","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0143417923000264","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
Naloxone could limit morphine hypersensitivity: Considering the molecular mechanisms
Background
Naloxone has been used as an opioid antagonist to prevent multiple adverse side effects of opioid-like tolerance and hyperalgesia. This study has investigated naloxone combined with morphine to limit pain hypersensitivity. In addition, the expression of brain-derived neurotrophic factor (BDNF) and K+ Cl− cotransporter2 (KCC2) were also studied.
Methods
Forty-eight adult male Wistar rats (180–220 g) were divided into eight groups, with six rats in each group. Rats were divided into two tolerance and hyperalgesia groups; the sham group, the morphine group, the treatment group (naloxone along with morphine), and the sham group (naloxone along with saline) for eight consecutive days. Tail-flick test was performed on days 1, 5, and 8, and the plantar test on days 1 and 10. On days 8 and 10, the lumbar segments of the spinal cord were collected, and BDNF and KCC2 expression were analyzed using western blotting and immunohistochemistry, respectively.
Results
Results showed that tolerance and hyperalgesia developed following eight days of repeated morphine injection. BDNF expression significantly increased, but KCC2 was downregulated. Co-administration of naloxone and morphine decreased tolerance and hyperalgesia by decreasing BDNF and increasing KCC2 expression, respectively.
Conclusion
This study suggests that BDNF and KCC2 may be candidate molecules for decreased morphine tolerance and hyperalgesia.
期刊介绍：
The aim of Neuropeptides is the rapid publication of original research and review articles, dealing with the structure, distribution, actions and functions of peptides in the central and peripheral nervous systems. The explosion of research activity in this field has led to the identification of numerous naturally occurring endogenous peptides which act as neurotransmitters, neuromodulators, or trophic factors, to mediate nervous system functions. Increasing numbers of non-peptide ligands of neuropeptide receptors have been developed, which act as agonists or antagonists in peptidergic systems.
The journal provides a unique opportunity of integrating the many disciplines involved in all neuropeptide research. The journal publishes articles on all aspects of the neuropeptide field, with particular emphasis on gene regulation of peptide expression, peptide receptor subtypes, transgenic and knockout mice with mutations in genes for neuropeptides and peptide receptors, neuroanatomy, physiology, behaviour, neurotrophic factors, preclinical drug evaluation, clinical studies, and clinical trials.
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