Peripherally restricted cannabinoid 1 receptor agonist as a novel analgesic in cancer-induced bone pain

Pain
Hong ZhangTodd Vanderah

Abstract

Many malignant cancers, including breast cancer, have a propensity to invade bones, leading to excruciating bone pain. Opioids are the primary analgesics used to alleviate this cancer-induced bone pain (CIBP) but are associated with numerous severe side effects, including enhanced bone degradation, which significantly impairs patients' quality of life. By contrast, agonists activating only peripheral CB1 receptors (CB1Rs) have been shown to effectively alleviate multiple chronic pain conditions with limited side effects, yet no studies have evaluated their role(s) in CIBP. Here, we demonstrate for the first time that a peripherally selective CB1R agonist can effectively suppress CIBP. Our studies using a syngeneic murine model of CIBP show that both acute and sustained administration of a peripherally restricted CB1R agonist, 4-{2-[-(1E)-1[(4-propylnaphthalen-1-yl)methylidene]-1H-inden-3-yl]ethyl}morpholine (PrNMI), significantly alleviated spontaneous pain behaviors in the animals. This analgesic effect by PrNMI can be reversed by a systemic administration but not spinal injection of SR141716, a selective CB1R antagonist. In addition, the cancer-induced bone loss in the animals was not exacerbated by a repeated administration ...Continue Reading

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Citations

Feb 6, 2019·Pain and Therapy·Ivan UritsOmar Viswanath
Feb 26, 2020·Neurosurgery·Teddy E KimWesley Hsu
Dec 29, 2019·Scientific Reports·David André BarrièrePhilippe Sarret
Apr 30, 2020·Current Opinion in Supportive and Palliative Care·Holly M Ellingson, Todd W Vanderah
Oct 19, 2019·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Jia SunDa-Wei Ye
Dec 1, 2019·The Journal of Pain : Official Journal of the American Pain Society·Herick Ulisses de OliveiraGiovane Galdino
Jan 29, 2021·Pharmacology, Biochemistry, and Behavior·Savanah L Saldaña-ShumakerChristopher W Cunningham
Jan 1, 2021·Frontiers in Pharmacology·Jorge B Pineda-FariasNicole N Scheff
Apr 28, 2020·Expert Opinion on Drug Discovery·Paula Morales, Nadine Jagerovic
Mar 1, 2019·Journal of Natural Products·Christopher W Cunningham

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