Figure 6: BDNF contributes to neuropathic pain induction through presynaptic GABAAR.
From: Presynaptic GABAergic inhibition regulated by BDNF contributes to neuropathic pain induction
(a) Current–voltage relationship for GABA-activated response from large (left) and small (right) neurons. (b) BDNF mimics the effect of nerve injury on EGABA and functional inhibition of BDNF-TrkB signalling reverses the depolarizing shift in EGABA (the number of neurons recorded is indicated in parentheses in each panel; unpaired t-test). (c) BDNF mimics the effect of nerve injury on GGABA and functional inhibition of BDNF-TrkB signalling reverses the reduction in GGABA (unpaired t-test). (d) The proportion of neurons displaying a GABA-evoked increase in [Ca2+]i was not different between control and BDNF-treated DRG neurons (control: large neuron: n=37, small n=207; BDNF: large neuron: n=22, small n=85; Fisher’s test, P>0.05). (e) Intrathecal administration of TrkB-Fc 2 days after nerve injury caused a significant increase in the paw withdrawal latency. n=6 mice/group (TrkB-Fc effect: two-way analysis of variance (ANOVA) with post-hoc Bonferroni test; ipsilateral+saline versus ipsilateral+TrkB-Fc, P<0.0001). Intrathecal injection of BDNF failed to induce heat hyperalgesia (f) in sns- β3−/− mice (n=6 mice per group, BDNF effect: one-way ANOVA with post-hoc Dunnett’s test; β3fl/fl, P<0.01; sns- β3−/−, P>0.05; β3fl/fl versus sns- β3−/−, two-way ANOVA, P<0.001), but did not affect the development of static mechanical allodynia (g) (n=6 mice/group, one-way ANOVA with post-hoc Bonferroni test; β3fl/fl, P<0.0001; sns- β3−/−, P<0.0001; β3fl/fl versus sns- β3−/−, two-way ANOVA, P<0.0001). *P<0.05; **P<0.01; ***P<0.001 versus control (b,c), or versus before injection (e,f). Error bars indicate s.e.m.
