A Compound Mitigates Cancer Pain and Chemotherapy-Induced Neuropathic Pain by Dually Targeting nNOS-PSD-95 Interaction and GABAA Receptor View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2021-11-18

AUTHORS

Wei Wei, Weili Liu, Shibin Du, Gokulapriya Govindarajalu, Antony Irungu, Alex Bekker, Yuan-Xiang Tao

ABSTRACT

Metastatic bone pain and chemotherapy-induced peripheral neuropathic pain are the most common clinical symptoms in cancer patients. The current clinical management of these two disorders is ineffective and/or produces severe side effects. The present study employed a dual-target compound named as ZL006-05 and examined the effect of systemic administration of ZL006-05 on RM-1–induced bone cancer pain and paclitaxel-induced neuropathic pain. Intravenous injection of ZL006-05 dose-dependently alleviated RM-1–induced mechanical allodynia, heat hyperalgesia, cold hyperalgesia, and spontaneously ongoing nociceptive responses during both induction and maintenance periods, without analgesic tolerance, affecting basal/acute pain and locomotor function. Similar behavioral results were observed in paclitaxel-induced neuropathic pain. This injection also decreased neuronal and astrocyte hyperactivities in the lumbar dorsal horn after RM-1 tibial inoculation or paclitaxel intraperitoneal injection. Mechanistically, intravenous injection of ZL006-05 potentiated the GABAA receptor agonist–evoked currents in the neurons of the dorsal horn and anterior cingulate cortex and also blocked the paclitaxel-induced increase in postsynaptic density-95–neuronal nitric oxide synthase interaction in dorsal horn. Our findings strongly suggest that ZL006-05 may be a new candidate for the management of cancer pain and chemotherapy-induced peripheral neuropathic pain. More... »

PAGES

1-13

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s13311-021-01158-8

DOI

http://dx.doi.org/10.1007/s13311-021-01158-8

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1142681797

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/34796458


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