Figure 7.

Functional impairment of PNN exposed to oxaliplatin. PNN (>DoD37) were used for Ca²⁺-imaging experiments to assess oxaliplatin-induced functional impairments. (A) Schematic representation of the experimental setup to assess responses toward a mechanical stimulus. (B) PNN were pre-treated with oxaliplatin (Oxali) according to (A). Cells received the P2X3 antagonist A-317491 (A31, 10 µM), or the Na_V channel inhibitors tetrodotoxin (TTX, 3 µM) or carbamazepine (Carb). The fractions of cells reacting with Ca²⁺-influx (ΔF > 18) were quantified. (C) Schematic representation of oxaliplatin exposure scenarios (a-d) before stimulation of cells by HBSS addition (see trigger mark). Some cells (a) did not receive oxaliplatin pre-treatment, while others (b) were pre-treated with oxaliplatin for 24 h prior to Ca²⁺ measurements. Condition (c) included pre-treatment with oxaliplatin for 1 h only. In scenario (d), a 24-h oxaliplatin pre-treatment was ended 2 h before Ca²⁺-measurement. (D) PNN were treated with oxaliplatin according to the scenarios (a-d), and reactive cells were quantified. Data in (B), (D) are means ± SEM, from 3-6 biological replicates. Significance was tested against condition a (*) or against condition b (#). */#P < .05, ***/###P < .001. (E, F) Effect of oxaliplatin pre-treatment (24 h) on (E) TRPV1 and (F) P2X3 PNN reactivity upon capsaicin or α,β-meATP stimulation (both 1 µM), respectively. Data points belonging to the same cell lot are color matched. Means ± SEM are given. Significance was tested against the respective control (0 µM). *P < .05, **P < .005, n.s. not significant.