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. 2023 Aug 14;2(8):pgad261. doi: 10.1093/pnasnexus/pgad261

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© The Author(s) 2023. Published by Oxford University Press on behalf of National Academy of Sciences.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

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Fig. 3. — Synergistic inhibition of Y1R and MOR is sufficient to induce immunohistochemical and behavioral markers of sensory and affective pain. A) Experimental timeline for PIM, i.t. pharmacology, light brush of the hind paw, and immunohistochemical staining for pERK immunoreactivity in the lumbar DH. B–E) Representative images of ipsilateral DH light-touched evoked pERK immunoreactivity after i.t. administration of agents. F) Intrathecally administered BIB03304:CTOP (10.0 ng) induces light-touched evoked pERK immunoreactivity in the ipsilateral DH. n = 3–4 mice/group. One-way ANOVA: F(3, 11) = 6.749, P = 0.0076; Dunnett's multiple comparison tests. G) Experimental protocol for CPA. H) BIB03304:CTOP (10.0 ng, i.t.) induces CPA in postincision but not postsham incision mice. n = 11–12 mice/group. Two-way ANOVA: interaction F(1, 42) = 4.606, P = 0.0377. Holm–Sidak post hoc test. Data are presented as mean ± SEM.