Wirt : Cannabinoid Receptor Type II Agonist LY2828360 Reverses Two Distinct Forms of Neuropathic Pain Without Producing Reward
Cannabinoid Receptor Type II Agonist LY2828360 Reverses Two Distinct Forms of Neuropathic Pain Without Producing Reward
Indiana University Bloomington
Jonah Wirt1,2,3; Kelsey Guenther1,2,3, Shahin Saberi1,2,3, Andrea Hohmann1,2,3
1. Psychological and Brain Sciences, Indiana University, Bloomington, IN
2. Program in Neuroscience, Indiana University, Bloomington, IN
3. Gill Center for Biomolecular Science, Indiana University, Bloomington, IN
Chronic pain remains one of the top reasons to seek medical care, and finding non-addictive therapeutic interventions remains a clinical imperative during an ongoing opioid epidemic. The endogenous cannabinoid system has shown promise in treating various types of pain, and the cannabinoid type II (CB2) receptor when agonized shows minimal central nervous system mediated side effects. We asked whether CB2 agonist LY2828360 would be efficacious in treating neuropathic pain.
Two distinct rodent models of neuropathic pain were used to assess CB2 receptor agonist LY2828360’s efficacy in rats. Sciatic nerve pain was induced by ligation of the common peroneal and sural branches. Chemotherapy-induced peripheral neuropathy was induced by administration of paclitaxel, a chemotherapeutic agent known to treat breast cancer, ovarian cancer, and lung cancer in humans. Conditioned place preference was used to assess addictive potential of LY2828360, and if LY2828360 could block the rewarding effects of morphine when combined.
LY2828360 reversed sciatic nerve injury-induced neuropathic pain. LY2828360 reversed ongoing neuropathic pain induced by chemotherapy and prevented the development of neuropathic pain while onboard when administered prophylactically when administered before and alongside chemotherapeutic treatment. LY2828360 did not produce rewarding effects on its own and blocked the rewarding effects of morphine in conditioned place preference testing.
LY2828360 shows promise in its ability to treat multiple neuropathic pain subtypes, without risk of abuse liability. In addition to this, LY2828360 also shows promise in reducing abuse liability of morphine itself and could be considered for combinatorial treatment to attenuate addictive potential of morphine given to pain patients.
Translational/Human Health Impact:
CB2 agonist LY2828360 could help reduce pain in chronic neuropathic pain patients without risk of abuse. LY2828360 could also be used in cancer treatment centers to prevent the development of neuropathic pain induced by chemotherapeutic treatment. Lastly, LY2828360 could be used to help reverse or prevent opioid abuse.
|2023-08-30T10:50:29-04:00August 30th, 2023|2023 Annual Meeting Presentations, Annual Meeting|Comments Off on Wirt : Cannabinoid Receptor Type II Agonist LY2828360 Reverses Two Distinct Forms of Neuropathic Pain Without Producing Reward