Archival ReportChronic Cannabinoid Receptor 2 Activation Reverses Paclitaxel Neuropathy Without Tolerance or Cannabinoid Receptor 1–Dependent Withdrawal
Section snippets
Subjects
Adult CB2KO mice, strain B6.129P2-CNR2(tm1Dgen/J) (Jackson Laboratory, Bar Harbor, Maine) and WT littermates (Jackson Laboratory) on C57BL/6J background, and CB1KO mice (generated as previously described (4)) and WT littermates (Charles River Laboratories, Wilmington, Massachusetts) on CD1 background, weighing 25–33 g and of both sexes, were used in these experiments. Mice were periodically backcrossed to maintain genetic integrity. Animals were single-housed in a temperature-controlled
Paclitaxel-Induced Allodynia Developed Similarly in WT, CB2KO, and CB1KO Mice
In both CB2KO and WT mice, paclitaxel decreased mechanical thresholds [F3,20 = 519.03, p < .0001] (Figure 1A) and increased response time to cold stimulation [F3,20 = 553.78, p < .0001] (Figure 1B). Similarly, paclitaxel induced mechanical [F3,20 = 426.66, p < .0001] (Figure 1C) and cold [F3,20 = 707.28, p < .0001] (Figure 1D) allodynia in CB1KO mice and WT littermates. Mechanical and cold allodynia were present in paclitaxel-treated CB2KO, CB1KO, and WT mice relative to cremophor-vehicle since
Discussion
Drug development for management of neuropathic pain has been a challenge partly because of limited efficacy and troubling side-effect profiles. These challenges also apply to potential therapeutic use of cannabinoids (44). In the present study, we showed that repeated systemic administration of the CB2-preferring agonist AM1710 suppressed chemotherapy-induced allodynia without tolerance or significant CB1 involvement (i.e., the absence of CB1 antagonist–precipitated withdrawal symptoms, motor
Acknowledgments and Disclosures
This work was supported by National Institute on Drug Abuse (NIDA) Grant Nos. DA021644 (AGH), DA037673 (AGH), DA011322 (KM), DA021696 (KM), DA3801 (AM), DA07215 (AM), DA09158 (AM), and DA035068 (KM and AGH). AM serves as a consultant for MAKScientific.
We thank Vishnu Kodumuru for providing AM1710 and James Wager-Miller for designing and providing the reverse transcription polymerase chain reaction primers.
The authors report no biomedical financial interests or potential conflicts of interest.
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