Fig. 5: TRPV1 KO mice are protected against bortezomib-induced neurotoxicity and loss of sensation in vivo.
From: Bortezomib-induced neuropathy is in part mediated by the sensitization of TRPV1 channels
a Top, In vivo dosing and behavioral measurement and anatomical studies schedule. Bottom, intraepidermal nerve fiber density (IENFD) assessed by PGP95 staining in WT mice treated with bortezomib treatment or vehicle. *: p < 0.05, Student’s T test (t = 3.267; df = 5). b IENFD assessed in TRPV1-cre::TdT mice to label TRPV1-lineage sensory neurons. In red, TdT signal, in green PGP9.5 staining and in blue DAPI signal. SC: stratum corneum, EP: epidermis, DR: dermis. Quantification classified vertical and non-vertical axons in the skin section. *: p < 0.05, Student’s T test (t = 2.287; df = 12 for vertical and t = 9.666; df = 12 for non-vertical) c Time spent in different temperature zones during the last 30 min of the thermal gradient assay in mice treated with saline and bortezomib and tested 14, 21, and 28 days after cessation of treatment. Preferred temperature is calculated by the best-fitted Gaussian curve and peak is indicated on top in °C. 95% confidence interval for temperature preference (in °C): Vehd14: 33.05 to 33.7; Vehd21: 33.03 to 33.71; Vehd28: 33.31 to 33.8; Bortd14: 27 to 29.7; Bortd21: 30.26 to 32.13 and Bortd28: 30.31 to 32.85). d Time spent in a zone of 40–50 °C (noxious temperature) in saline and bortezomib treated mice tested 14, 21, and 28 days after cessation of treatment. *: p < 0.05 compared to veh d14 (*, p < 0.05 Sidak’s test, t = 5.347, df = 5.352). e IENFD in TRPV1 KO mice treated with saline or bortezomib. f Time spent in different temperature zones during the last 30 min of the thermal gradient assay in TRPV1 KO mice treated with saline or bortezomib and tested 14 days after cessation of treatment. Preferred temperature is calculated by the best-fitted Gaussian curve and peak is indicated on top in °C. 95% confidence interval for temperature preference (in °C): Veh: 31.17–32.92; Bort: 30.57–32.71). For anatomy, n = 3–6 mice per group. For behavior: 5–6 mice per group. Data presented as mean ± SEM. Dots represent individual animals. Scale bar represents 50 µm.
