Figure 4.
Sustained modulatory effect on heat hyperalgesia with the single- and multisession tFUS stimulation in female HbSS-BERK mice. (A) Experimental design for the single-session treatment with behavioral study. (B) The averaged Δ hPWL stimulated by single-session tFUS with a PRF of 40 Hz at left insula (n = 10) was significantly increased up to 30 minutes in HbSS-BERK mice compared with the pre-tFUS baseline, as well as values from sham (n = 10) and negative control groups (n = 10). Single-session tFUS with a PRF of 3 kHz (n = 10), sham treatment, and negative control did not result in remarkable changes in Δ hPWL compared with the baseline. ∗P < .05, ∗∗P < .01 using 1-way analysis of variance (ANOVA) with Friedman test; #P < .05, ##P < .01, ###P < .001 using 1-wayANOVA with Kruskal-Wallis test. (C) Targeting the thalamus with tFUS using a PRF of 40 Hz (n = 10) and 3 kHz (n = 10) did not result in a prominent modulatory effect compared with the prestimulation baseline, as well as sham-treated mice (n = 10) and negative control mice (n = 10), except for 2 measurements (right panel: #P = .0104, 8 minutes after tFUS with the PRF of 40 Hz and sham treatment; #P = .0277, 60 minutes after tFUS with the PRF of 40 Hz and negative control). ns, not significant, #P < .05 using 1-way ANOVA with Kruskal-Wallis test. (D) Sustained amelioration of heat hyperalgesia was examined in older female HbSS-BERK mice (10 to 15-month-old) by measuring latency to noxious heat stimuli compared with prestimulation baseline upon 14-day tFUS stimulation. (E) After multisession tFUS stimulation with a PRF of 40 Hz to S1HL (n = 11) or insula (n = 10) for 14 days, the averaged changes of Δ hPWL were significantly increased for at least 2 hours compared with the baseline values, as well as sham-treated behavioral change (n = 4). The measurement was conducted at 2 hours after tFUS or sham treatment, indicating that the effect of multisession tFUS stimulation is considered to persist for at least 2 hours. ns, not significant, ∗P < .05, ∗∗∗P < .001 using t test with Wilcoxon 1-tailed signed rank test; #P < .05, ##P < .01 using t test with 1-tailed Mann-Whitney test. ns, not significant.

Sustained modulatory effect on heat hyperalgesia with the single- and multisession tFUS stimulation in female HbSS-BERK mice. (A) Experimental design for the single-session treatment with behavioral study. (B) The averaged Δ hPWL stimulated by single-session tFUS with a PRF of 40 Hz at left insula (n = 10) was significantly increased up to 30 minutes in HbSS-BERK mice compared with the pre-tFUS baseline, as well as values from sham (n = 10) and negative control groups (n = 10). Single-session tFUS with a PRF of 3 kHz (n = 10), sham treatment, and negative control did not result in remarkable changes in Δ hPWL compared with the baseline. ∗P < .05, ∗∗P < .01 using 1-way analysis of variance (ANOVA) with Friedman test; #P < .05, ##P < .01, ###P < .001 using 1-wayANOVA with Kruskal-Wallis test. (C) Targeting the thalamus with tFUS using a PRF of 40 Hz (n = 10) and 3 kHz (n = 10) did not result in a prominent modulatory effect compared with the prestimulation baseline, as well as sham-treated mice (n = 10) and negative control mice (n = 10), except for 2 measurements (right panel: #P = .0104, 8 minutes after tFUS with the PRF of 40 Hz and sham treatment; #P = .0277, 60 minutes after tFUS with the PRF of 40 Hz and negative control). ns, not significant, #P < .05 using 1-way ANOVA with Kruskal-Wallis test. (D) Sustained amelioration of heat hyperalgesia was examined in older female HbSS-BERK mice (10 to 15-month-old) by measuring latency to noxious heat stimuli compared with prestimulation baseline upon 14-day tFUS stimulation. (E) After multisession tFUS stimulation with a PRF of 40 Hz to S1HL (n = 11) or insula (n = 10) for 14 days, the averaged changes of Δ hPWL were significantly increased for at least 2 hours compared with the baseline values, as well as sham-treated behavioral change (n = 4). The measurement was conducted at 2 hours after tFUS or sham treatment, indicating that the effect of multisession tFUS stimulation is considered to persist for at least 2 hours. ns, not significant, ∗P < .05, ∗∗∗P < .001 using t test with Wilcoxon 1-tailed signed rank test; #P < .05, ##P < .01 using t test with 1-tailed Mann-Whitney test. ns, not significant.

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