Fig. 2
Multiple intrathecal 2R, 6R-HNK provides a sustained analgesic effect on chronic pain induced by LF-PENS. a Schematic overview of experiments for intrathecal injections of 2R, 6R-HNK (21, 42 μM, 10 μl, since 4 d after LF-PENS, at 5-days intervals) or saline and a variety of behavioral tests in LF-PENS-induced chronic pain model. OFT, open field test; EPM, elevated plus maze test; SPT, sucrose preference test; FST, forced swim test; TST, tail suspension test; NOR, new object recognition test; IF, immunofluorescence. Blue or red triangles indicated the time point of drugs/saline or LF-PENS treatments. As the same in the follows (n = 5 ~ 8 mice/group). b Representative images of LF-PENS (2 Hz, 0.5 ms, 10 V, a total of 120 pulses for 1 min) of the left popliteal fossa. c Tail suspension test showed normal hind-limb splay at 4 d after LF-PENS. d No difference of the walking speed was noticed within 10 min among the groups. e The time course of Ipsi- or Contr-PWT to respond to mechanical stimulus following LF-PENS with multiple intrathecal treatments of saline or 2R, 6R-HNK (21, 42 μM). f 2R, 6R-HNK dose-dependently reversed LF-PENS-induced cold hyperalgesia. Acetone tests were performed at 15–18 d after LF-PENS. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001 versus the LF-PENS + saline group; #p < 0.05, ##p < 0.01, ###p < 0.001 versus the LF-PENS + 21 μM HNK group; $$p < 0.01 versus Day 8th or 9th after LF-PENS