Fig. 6

GPER/β-alanine positive feedback interaction in the dorsal root ganglion (DRG) mediating neuronal sensitization and neuroinflammation responses. A Itch allodynia and mechanical allodynia and cold hyperalgesia were developed rats administered intrathecal β-alanine rat after 24 h (n = 6, two-tailed Student’s t test. ^**p < 0.01 versus Vehicle). B β-Alanine content in the DRG of rats in the Sham, SNI, and SNI + G15, and SNI + GABA groups (n = 3, one-way ANOVA. ^**p < 0.01 versus sham; ^##p < 0.01 versus SNI; ^$$p < 0.01 versus sham). C β-Alanine content in the DRG of rats in the Vehicle, G1, and G15 groups. two-tailed Student’s t test. ^*p < 0.05, ^**p < 0.01 versus Vehicle. D β-alanine content in DRG of rats in the Sham and SNI Day 3, 5, 7, and 14 groups. (One-way ANOVA followed by Tukey’s test. ^**p < 0.01, ^***p < 0.001 versus the sham group.); n = 3. E Western blot images for GPER, ERα, ERβ, IL-6, IL-1β, and GABAα2 in the DRG after intrathecal injection of β-alanine and G15 in rats. F GPER, IL-6, and IL-1β protein level were increased, GABAα2 downregulated in the dorsal root ganglion (DRG) of β-alanine group rats. (n = 3, two-tailed Student’s t test. ^**p < 0.01, ^***p < 0.001 versus vehicle). G Quantification for GPER, ERα, ERβ, and GABAα2 in the DRG after intrathecal injection of G15. Except GPER protein downregulated, IL-6, IL-1β, and GABAα2 had no significant. H Current threshold (rheobase) was determined as the current required for activating the first action potential. On the left, representative traces of action potentials (APs) evoked by current injections into DRG neurons from Sham, SNI, SNI + G15, G1, and β-alanine groups; n = 4–6 neurons per group; on the right, the number of action potentials produced at the corresponding 2 × rheobase. I Statistical analysis revealed the rheobase; size of neurons, membrane capacitance, and number of action potentials (APs) at 2 × rheobase in DRG neurons. n = 4–6 neurons per group. One-way ANOVA followed by Tukey’s test. ^**p < 0.01 versus sham; ^#p < 0.05, ^##p < 0.01 versus SNI; ^&p < 0.05, ^&&p < 0.01 versus sham; ^$$p < 0.01 versus sham. β-ALA: β-alanine