Fig. 4.
Selective knockdown of the α2 subunit in the ipsilateral L5 dorsal root ganglion neurons of sham animals mimics the neuropathic pain phenotype caused by crush injury of a sciatic nerve in adult female rats. (A) Thermal withdrawal latencies (PWLs) were measured in rats that had sham surgery (at day 0, marked with an arrow as SURGERY) followed by antisense (AS) oligodeoxynucleotides (ASODN) treatment on postoperative day (POD) 2 (marked with an arrow as AS) after the lack of thermal hypersensitivity was confirmed. The knockdown of the α2 subunit with ASODNs resulted in a significant decrease in PWLs on POD 3 through 5 (outlined with dashed rectangle) (n = 5 per data point) (†††P < 0.001, before and after ASODN treatment; ***P < 0.001; **P < 0.01, PWLs in operated [right paw] paw vs. unoperated [left paw] paw at PODs 3, 4, and 5). (B) Thermal PWLs were measured in rats that had sham surgery followed by mismatch (MIS) oligodeoxynucleotides (MISODN) treatment on POD 2 (marked with an arrow as MIS) after the lack of thermal hypersensitivity was confirmed. There was no change in PWLs in MISODNs animals at any time point (n = 4 per rats data point). (C) Mechanical hypersensitivity in sham-operated animals post-ASODN treatment measured as a significant increase in paw withdrawal responses (PWRs) was noted on POD 3 through 8 (outlined with dashed rectangle) (††P < 0.01, †††P < 0.001, before and after ASODNs treatment, ***P < 0.001, PWRs in operated [right paw] paw vs. unoperated [left paw] paw) (n = 5 rats per data point). (D) In sham-operated animals post-MISODNs treatment, there was no change in mechanical sensitivity shown as stable PWRs recordings throughout the testing period (n = 4 rats per data point).