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. 2016 Aug 18;157(12):2709–2721. doi: 10.1097/j.pain.0000000000000690

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© 2016 International Association for the Study of Pain

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Figure 3. — Antinociceptive effects of Ang-(1-7) through MasR are maintained after repeated administration. Spontaneous pain behaviors guarding (A) and flinching (B) were recorded in a 2-minute period before surgery, after surgery (7 days after inoculation), and after drug administration on days 10 and 14. Daily administration of Ang-(1-7) (0.058 μg/kg, i.p.) significantly reduced spontaneous pain behaviors associated with cancer-induced bone pain (CIBP) (P < 0.0001). Furthermore, tactile allodynia was recorded before surgery, after surgery (7 days after inoculation), and after drug administration on days 10 and 14. Cancer inoculation significantly reduced paw withdrawal thresholds 7 days after surgery (P < 0.05, n = 12). To investigate receptor dependence, animals were dosed postsurgery days 7 to 14 with A-779 (0.19 μg/kg, i.p.) 30 minutes before administration of Ang-(1-7). Spontaneous pain behaviors guarding (C) and flinching (D) were recorded as previously described. Daily administration of A-779 reversed the effects of Ang-(1-7) in the CIBP model. Animals experienced significant (P < 0.05, n = 12) increase in the paw withdrawal threshold (E) after Ang-(1-7) treatment on postsurgery day 14. Values represent mean ± SEM, n = 12 per group.