Fig 4.

Intrathecal (i.t.) administration of nerve injury-specific long non-coding RNA (NIS-lncRNA) antisense oligonucleotides (ASOs) attenuated the streptozotocin (STZ)-induced NIS-lncRNA increase in dorsal root ganglion (DRG) and nociceptive hypersensitivity. ASOs (100 μg) or phosphate buffered saline (PBS) 0.01 M was injected intrathecally on day 14 after STZ or vehicle 2 (Veh2) injection. (a) Level of NIS-lncRNA in the unilateral lumbar 3/4 DRGs on day 35 after STZ or vehicle 2 injection in the mice with treatments as indicated. n=3 repeats (6 mice)/group. ∗∗P<0.01, by two-way anova followed by post hoc Tukey test. (b–h) Effect of i.t. administration of NIS-lncRNA ASOs or PBS on paw withdrawal frequency (PWF) to 0.07 g (b and f) and 0.4 g (c and g) von Frey filament stimuli and paw withdrawal latency (PWL) to heat (d and h) and cold (e) stimuli on the left (b–e) and right (f–h) sides on days as indicated after STZ or vehicle 2 injection. n=8–10 mice/group. ∗∗P<0.01 vs the STZ plus PBS-treated group at the corresponding days, by three-way anova with repeated measures followed by post hoc Tukey test. (i and j) Effect of i.t. administration of NIS-lncRNA ASOs or PBS on ongoing nociceptive responses as assessed by the conditioned place preference paradigm on day 28 after STZ or vehicle 2 injection. Post, post-conditioning; Pre: preconditioning. n=8–10 mice/group. ∗∗P<0.01, by three-way anova with repeated measures followed by post hoc Tukey test (i) or two-way anova followed by post hoc Tukey test (j). (k) Effect of i.t. administration of NIS-lncRNA ASOs or PBS on the levels of phosphorylated extracellular signal-regulated kinase 1 and 2 (p-ERK1/2), ERK1/2, and glial fibrillary acidic protein (GFAP) in the unilateral lumbar 3/4 dorsal horn 35 days after STZ or vehicle 2 injection. GAPDH (glyceraldehyde-3-phosphate dehydrogenase) was used as a control. n=3 repeats (6 mice)/group. ∗∗P<0.01, by two-way anova followed by post hoc Tukey test.