Figure 5: Pain behaviour in nociceptor-specific presynaptic GABAAR knockout (KO) mice and littermate controls.
From: Presynaptic GABAergic inhibition regulated by BDNF contributes to neuropathic pain induction
(a) Scheme illustrating the specific KO of GABAAR in nociceptors. (b) Representative traces of GABA-activated currents recorded in large (left) and small (right) DRG neurons clamped at −60 mV from β3fl/fl and sns- β3−/− mice. (c) Statistical analysis shows the amplitude of GABA-activated current is significantly reduced in small but not in large DRG neurons from sns- β3−/− mice compared with β3fl/fl mice; large neuron: P>0.05; small neuron: P<0.01, unpaired t-test. (d) Quantification of gabaβ3 gene transcripts in the DRGs and spinal cord of sns- β3−/− and their WT littermates. DRG: P<0.05; spinal cord: P>0.05; n=9 for each. (e) Hargreaves: sns- β3−/− mice exhibit higher sensitivity to noxious heat stimulation (β3fl/fl: n=12; sns- β3−/−: n=12. P<0.0001). (f) Dynamic Plantar Aesthesiometer: sns- β3−/− mice show increased sensitivity to noxious mechanical stimulation (β3fl/fl: n=12; sns- β3−/−: n=12. P<0.0001). (g) Von Frey: mechanical threshold were measured using Von Frey hairs (β3fl/fl: n=6; sns- β3−/−: n=6. P<0.01). (h) Bicuculline increased thermal sensitivity of both sns- β3−/− and their WT littermates. n=6 mice per group (β3fl/fl: saline versus bicuculline, P<0.0001; sns- β3−/−: saline versus bicuculline, P<0.0001; saline: β3fl/fl versus sns- β3−/−, P<0.0001; bicuculline: β3fl/fl versus sns- β3−/−, P>0.05). (i) sns- β3−/− mice failed to develop thermal hypersensitivity after CCI. n=6 mice per group. (Two-way analysis of variance (ANOVA): β3fl/fl contralateral versus ipsilateral, P<0.0001; sns- β3−/− contralateral versus ipsilateral, P=0.0457; β3fl/fl ipsilateral versus sns- β3−/− ipsilateral after injury, P>0.05). (j) Dynamic mechanical hypersensitivity is significantly reduced in sns- β3−/− mice. n=6 mice per group. (Two-way ANOVA: β3fl/fl contralateral versus ipsilateral, P<0.0001; sns- β3−/− contralateral versus ipsilateral, P=0.0004; β3fl/fl ipsilateral versus sns- β3−/− ipsilateral after injury, P>0.05). (k) Static mechanical allodynia is not affected in sns- β3−/− mice. n=6 mice per group (Two-way ANOVA, P<0.0001). Error bars indicate s.e.m. *P<0.05; **P<0.01; ***P<0.0001.
