Figure 1

Thermal hyperalgesia (TH) caused by intraplantar injection of acid in thrombus-induced ischemic pain (TIIP) rats. (A) Long-term effects of acid (D0-3 post-surgery) induced TH in TIIP rats. We evaluated TH of sham control rats (pH 7.0 and 4.0, n = 7 and 5 in each group) and TIIP rats (pH 7.0, 5.5 and 4.0, n = 5, 5 and 9 in each group) at day 1, 2, 3, 5, 7 and 12 after the surgery. TH was measured 2 hours after saline injection to avoid its acute effects. Only in the TIIP + pH 4.0 saline (acidic saline injected TIIP, AS-TIIP) group, did significant TH develop beginning on day 1 after the injection of pH 4.0 saline and continuing for the duration of the injection period (**P < 0.01, ***P < 0.001 vs sham + pH 7.0 saline). (B) Short-term effects of acid-induced TH in TIIP rats at day 1 post-surgery. We evaluated TH in sham and TIIP rats following injection of pH 4.0 saline (n = 6 in each group) at 30 min, 1, 2, 4, 8 and 12 hours after pH 4.0 saline injection. After pH 4.0 saline injection, AS-TIIP rats showed prominent TH compared to sham rats; TH was observed from 30 min to 8 hours post-injection (*P < 0.05, **P < 0.01 and ***P < 0.005 vs sham + pH 4.0 saline). (C) Short-term effects of acid-induced TH in TIIP rats at day 3 post-surgery. We evaluated TH in sham and TIIP rats following injection of pH 4.0 (n = 6 in each group) at 30 min, 1, 2, 4, 8 and 12 hours after pH acid injection. Significant TH was present in AS-TIIP rats prior to pH 4.0 saline injections. Following pH 4.0 saline injections, AS-TIIP rats showed sustained TH, which did not recover until 12 hours post-injection (**P < 0.01, ***P < 0.001 vs sham + pH 4.0 saline).