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. 2018 Dec 28;160(1):136–150. doi: 10.1097/j.pain.0000000000001386

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Copyright © 2018 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain.

This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

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Figure 2. — Repeated CBD treatment increases paw withdrawal threshold and prevents anxiety-like behavior in the OFT, EPMT, and NSFT after SNI surgery. (A) Scheme illustrating the timing of SNI induction, behavioral and electrophysiological experiments. (B) Mechanical hypersensitivity was measured with von Frey filaments at day 15 (D0), 19 (D5), and 23 (D7) after SNI surgery. Sham rats treated with veh (n = 6) or CBD (5 mg/kg/day, subcutaneously [s.c.], for 7 days, n = 6) and SNI rats treated with veh (n = 9) and CBD (5 mg/kg/day, s.c., for 7 days, n = 9) were tested. Each point of the line represents mean ± SEM expressed as mean of 50% paw withdrawal threshold (g). Three-way ANOVA followed by Bonferroni post hoc comparisons. ***P < 0.001 vs sham/veh; ###P < 0.001 vs SNI/veh at D7. (C) Horizontal movement traces in the OFT of sham and SNI rats treated with veh or CBD (5 mg/kg/day, s.c., for 7 days). (D-F) Distance travelled (cm) (D), time spent (s) in the central area (E), and number of entries in the central area (F) of the OFT. Sham rats treated with veh (n = 9) or CBD (5 mg/kg/day, s.c., for 7 days, n = 9) and SNI rats treated with veh (n = 9) and CBD (5 mg/kg/day, s.c., for 7 days, n = 9) were tested. Each bar represents mean ± SEM. In D-F, each point represents data from an individual rat. Two-way ANOVA followed by Bonferroni post hoc comparisons. *P < 0.05 and ***P < 0.001 vs sham/veh; ###P < 0.001 vs SNI/veh. (G) Time of immobility (s) in the FST. (H and I) Percentage of time (%) (H) spent in the open arms in the EPMT and head dipping duration (s) (I). Each bar represents mean ± SEM. (J) Horizontal movement traces in the EPMT of sham and SNI rats treated with veh or CBD (5 mg/kg/day, s.c., for 7 days). (K and L) Latency to feed (s) in the novel (K) and familiar (L) environments in the NSFT. Each symbol represents mean ± SEM. Sham rats treated with veh (n = 8) or CBD (5 mg/kg/day, s.c., for 7 days, n = 9) and SNI rats treated with veh (n = 9) and CBD (5 mg/kg/day, s.c., for 7 days, n = 9) were tested. In G-I, each point represents data from an individual rat. Two-way ANOVA followed by Bonferroni post hoc comparisons. **P < 0.01 vs sham/veh., #P < 0.05, and ##P < 0.01 vs SNI/veh. ANOVA, analysis of variance; CBD, cannabidiol; EPMT, elevated plus maze test; FST, forced swim test; N.S., not significant; NSFT, novelty-suppressed feeding test; OFT, open-field test; SNI, spared nerve injury.