Fig. 7: PreNMDARs and its downstream target BDNF in nociceptors are required for the behavioral manifestation of nociceptive hypersensitivity.
a, b Secondary hyperalgesia and allodynia to von Frey hairs applied to the plantar surface of the paw, which lies outside of the flare evoked by capsaicin injection to the lower thigh, developed to a much lower degree in SNS-NR1−/− mice than NR1fl/fl mice (n = 8). Shown are stimulus-response curves (a) and the summary of response thresholds to von Frey hair to the hindpaw prior to and at 15, 40 min following capsaicin injection (b). *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001 by Kruskal–Wallis H test. c, d Intrathecal injection of NMDARs antagonist, AP-5 (1 mM) inhibited capsaicin-induced secondary mechanical hypersensitivity in NR1fl/fl mice (left panel), but not in SNS-NR1−/− mice (right panel). Quantitative summary is shown in (d) (n = 10). *P < 0.05, **P < 0.01, ****P < 0.0001 by Kruskal–Wallis H test. e Following injection of acidic saline in the flank muscle, increase of response frequency to von Frey hairs is much greater in NR1fl/fl mice than SNS-NR1−/− mice in both ipsilateral (upper panels) and contralateral (lower panels) hindpaws (n = 4 for NR1fl/fl, n = 5 for SNS-NR−/−). f Summary of mechanical response thresholds to von Frey hairs application to the ipsilateral (upper panel) and contralateral (lower panel) paws, prior to and at different time points following muscular injection in NR1fl/fl and SNS-NR1−/− mice. *P < 0.05 at all time points for NR1fl/fl vs basal, †P < 0.05 at all time points for NR1fl/fl vs SNS-NR1−/− by Friedman M test. g Specific knockdown of BDNF in nociceptors reduced capsaicin-induced secondary mechanical hypersensitivity. Shown are stimulus-response curves to von Frey hairs applied to hindpaws following capsaicin injection into the flank in SNS-Cre mice expressing shRNA BDNF and shRNA control in the L3/L4 DRGs (n = 4). *P < 0.05, ***P < 0.001 by Friedman M test. Data are represented as mean ± S.E.M. See Supplemental Table 2 for detailed statistical information. Cap, capsaicin.
