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. 2022 Dec 29;24(1):582. doi: 10.3390/ijms24010582

Figure 2.

Figure 2

αN-acetyl β-End 1–31 exhibited antiallodynic effects and reduced β-End 1–31 and morphine analgesia. Implication of σ1Rs. (A) Effect of αN-acetyl β-End 1–31 on the mechanical allodynia induced by chronic constriction injury (CCI) of the sciatic nerve. Upper panel: the withdrawal thresholds of the contralateral and ipsilateral paws were measured before (indicated as 0) and up to 14 days after surgery. The force (in grams) at which the mice withdrew their paws in response to von Frey hair stimulation was determined as an index of mechanical allodynia. * Significantly different from the value of the contralateral paw. Middle panel: 0.3 and 3 nmol of αN-acetyl β-End 1–31 were administered icv 7 days after surgery, and the nociceptive threshold was evaluated at the indicated postinjection intervals (in minutes). For every time interval studied in min or days, * indicates a significant difference from the group that received saline instead of αN-acetyl β-End 1–31; ϕ significant difference from the effect of 3 nmol αN-acetyl β-End 1–31. Lower panel: the antiallodynic effect of 3 nmol αN-acetyl β-End 1–31 was diminished by coadministration of 3 nmol PRE084. * Significantly different from the group which received saline instead of αN-acetyl β-End 1–31. ϕ Significantly different from the group that received only αN-acetyl β-End 1–31. All data are presented as the mean ± SD of six mice. ANOVA followed by the Holm–Sidak multiple comparisons test, p < 0.05, 1-β > 0.80. (B) Effect of αN-acetyl β-End 1–31 on morphine and β-End 1–31 analgesia in mice. Upper panel: wild-type mice were injected icv with saline, αN-acetyl β-End 1–31 (1 nmol/mouse) or the combination of the σ1R agonist PPCC (3 nmol/mouse) plus αN-acetyl β-End 1–31 20 min before morphine and β-End 1–31. Analgesia was evaluated by the warm water (52 °C) tail-flick test at the interval postinjection corresponding to their peak effect, 30 min. Lower panel: σ1R−/− mice received 1 nmol αN-acetyl β-End 1–31, 20 min before morphine and β-End 1–31 and analgesia was evaluated as described above. Eight mice were used per strain and treatment. * Significant difference with respect to the group treated with morphine or β-End 1–31 alone. ANOVA followed by the Holm–Sidak multiple comparisons test, p < 0.05, 1-β > 0.80.