Fig. 1: CV2/CRMP5-Abs labels nociceptive structures and induces mechanical hypersensitivity and DRG neuron hyperexcitability.

A Micrographs of rat dorsal root ganglia (DRG) and spinal cord immunolabelled with anti-CV2 sera from three patients. The right panels show a magnification of boxed regions of spinal cord sections. The experiment was repeated across five rats with consistent results. B Representative recordings of evoked action potentials recorded from small-diameter DRG neurons in response to depolarizing current injection of 30, 60, and 90 picoamperes (pA). Female rat DRG neurons were treated overnight with serum from patient #4 or #6 (1/100 dilution). C Quantification of the number of evoked action potentials in response to 0–100 pA of injected current. *p < 0.05, multiple Mann–Whitney tests. PBS n = 11 cells, Patient #4 n = 11 cells, Patient #6 n = 11 cells, obtained from at least three rats. D Representative traces of rheobase recordings from cells treated with PBS, serum from patient #4, or #6. E Bar graph with scatter plot showing a decreased rheobase in neurons treated with serum from patient #4 or #6. PBS n = 14 cells, Patient #4 n = 10 cells, Patient #6 n = 12 cells; error bars indicate mean ± SEM, *p < 0.05, Kruskal–Wallis test. F Graph showing the paw withdrawal threshold of male rats injected intrathecally (i.th.) with 10 µL of the indicated positive CV2/CRMP5-Abs or (G) depleted (cross-adsorbed with purified CRMP5) sera. n = 12; 3 rats per CV2/CRMP5-Abs serum; 4 different CV2/CRMP5-Abs sera. The black line shows the average of all patients tested. two-way ANOVA. H Bar graph with scatter plot showing the area under the curve for the data in (F, G), *p < 0.05, two-tailed, Mann–Whitney test. All data are shown with error bars that indicate mean ± SEM. See Supplementary Data 1 for additional statistical details. Source data are provided as a Source Data file.