Fig. 1

Intrathecal 2R, 6R-HNK exerts delayed antinociceptive effects on HFS-induced acute and chronic pain. a Intrathecal (i.t. 7, 21 μM, 10 μl) or intraperitoneal (i.p. 10 mg·kg⁻¹) 2R,6R-HNK (HNK) reversed the reduction of the ipsilateral (Ipsi-) or contralateral (Contr-) paw withdrawal threshold (PWT) at 3 w after 10 V high-frequency-stimulation (HFS) of left sciativ nerve (n = 5 mice/group). Blue triangles indicated the time point of saline or drugs treatment ( the same in the follows). b Intrathecal preadministration of 2R, 6R-HNK rather than S-Ketamine (Ket) at the roughly same dosages (7, 21 μM) delayed HFS-induced acute mechanical pain. 2R, 6R-HNK, S-Ketamine or saline was intrathecally delivered 30 min before HFS. Red triangles showed the time point of sham operation or HFS delivered to sciatic nerve. ^*p < 0.05, ^**p < 0.01, ^***p < 0.001, ^****p < 0.0001 versus the HFS + saline i.t. or Saline i.t. + HFS group; ^#p < 0.05, ^##p < 0.01, ^###p < 0.001, ^####p < 0.0001 versus the HFS + 10 mg·kg⁻¹ HNK i.p. or 7 μM Ket i.t. + HFS group; ^$p < 0.05, ^$$p < 0.01, ^$$$p < 0.001, ^$$$$p < 0.0001 versus the HFS + 7 μM HNK i.t. or 7 μM HNK i.t. + HFS group