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. 2009 May 13;29(19):6217–6228. doi: 10.1523/JNEUROSCI.0893-09.2009

Figure 7.

Figure 7.

Antisense oligodeoxynucleotides to TRPC6 reverses 4α-PDD-induced hyperalgesia to mechanical and hypotonic stimuli. A, Intradermal injection of 4 α-PDD (1 μg/2.5 μl) in rat hindpaw 30 min before measurement of nociceptive thresholds induced a significant decrease in mechanical thresholds (120 ± 1 g, n = 8 for baseline vs 76 ± 1 g,; n = 8 after 4α-PDD; *p < 0.0001, paired Student's t test). In contrast, intradermal injection of the vehicle, 10% DMSO, had no significant effect on mechanical thresholds (n = 4 before and after 10% DMSO; p > 0.05, paired Student's t test). BL, Baseline. B, Treatment with TRPC6 antisense (AS) ODN for 3 d reversed the mechanical hyperalgesia induced by 4α-PDD compared with mismatch-treated (MM) rats (n = 8 for baseline and n = 6 for each ODN group; *p < 0.001, Tukey's post hoc multiple comparison test). The effect of the antisense was reversible; 4 d after the last ODN injection, the mechanical thresholds was similar in baseline and ODN-treated rats (p > 0.05, Tukey's multiple comparison test). In contrast, treatment with TRPC1 antisense ODN does not affect the decrease in mechanical threshold induced by 4α-PDD (p > 0.05, Tukey's post hoc multiple comparison test). C, Intradermal injection of 4α-PDD in rat hindpaw induces a significant number of flinches (15 ± 1, n = 6). Moreover, rats pretreated with 4α-PDD have a sixfold increase in the number of nociceptive flinches in response to an injection of hypotonic solution (4 ± 1, n = 12 for hypotonic in the absence and 24 ± 3, n = 10 in the presence of 4α-PDD; p < 0.0001, unpaired Student's t test). Treatment with TRPC6 antisense ODN markedly reduced the number of flinches induced by intradermal injection of hypotonic solution in the presence of 4α-PDD compared with mismatch-treated rats (24 ± 3, n = 10 for baseline 4α-PDD plus hypotonic solution; 8 ± 1, n = 6 for antisense-treated rats; and 20 ± 1, n = 6 for mismatch-treated rats; *p < 0.001, Tukey's post hoc multiple comparison test). Again the effect of antisense was reversible; 4 d after the last ODN injection, the number of flinches was not significantly different between TRPC6 antisense- and mismatch-treated rats. In contrast, antisense ODN to TRPC1 did not affect the number of flinches (n = 10 for baseline 4α-PDD plus hypotonic solution and n = 6 for ODN groups; p > 0.05, Tukey's post hoc multiple comparison test).

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