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. Author manuscript; available in PMC: 2024 Oct 1.
Published in final edited form as: Brain Behav Immun. 2023 Aug 7;113:401–414. doi: 10.1016/j.bbi.2023.08.005

Fig. 4. Timp3 controls mechanical and thermal sensitivities in naïve mice.

Fig. 4.

(A) Schematic illustration of the experiment showing the timeline of siRNA injections, pharmacological and biochemical studies. (B) Western blot representative image and quantification show that Timp3 siRNA significantly decreases Timp3 protein levels in DRGs tissues (n=4). (C) Timp3 siRNA injections do not cause locomotor dysfunction in the Rota-rod test (n=5). (D) Mechanical and thermal (von Frey, Hargreaves, and dry ice) allodynia induced by Timp3 siRNA compared to a control (Ctrl) non-targeting siRNA (2 μg of siRNA per delivery in the transfection agent PEI, n=7). (E) Anti-allodynic effect of exogenous recombinant TIMP3 (rTIMP3, 100 ng/site, i.t.), general endogenous tissue inhibitor of MMPs (TIMP-1, 4 pmol/site), MMP2 and MMP14 inhibitors (10 μg/site, i.t.), TACE/ADAM17 inhibitor (TAPI-2, 1 μg/site, i.t.), and a neutralizing antibody for TNF-α (5 μg/site, i.t.) on mechanical allodynia induced by Timp3 siRNA on day 2. (F) Anti-TIMP3 antibody (TIMP3 Ab, 10 μg/site, i.t.) induces mechanical allodynia compared to IgG control in male and female mice. BL = baseline. Data are expressed as mean ± SEM and statistically analyzed by two-tailed t-test (B, C, E) and Two-way ANOVA followed by Sidak’s post hoc test (D, F). *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.