Fig. 6

Restoration of noxious stimulus induced analgesia (NSIA) by chemogenetic inhibition of LC in SNL6W rats. (A) The course of the experiment. Inhibitory DREADD containing AAV (Gi) or control AAV (control) containing only mCherry were injected in the bilateral LC of SNL animal approximately 4 weeks before the test day. Capsaicin was injected subcutaneously at the left forepaw 1 h after the intraperitoneal CNO (clozapine-N-oxide, 1 mg/kg i.p.) administration, and changes in paw withdrawal threshold were examined with paw pressure test over time (baseline 0, 30, 60, 90, and 120 min). The differences in the withdrawal threshold following capsaicin injection (Δg) were shown in (B). The withdrawal threshold of Gi-DREADD-treated group (Gi-cap) increased compared with the value of before capsaicin injection. This indicates that the inhibition of LC activity can produce capsaicin induced NSIA like effects. The data are expressed as the mean ± SD. n = 6 rats for each group. * p < 0.05 versus time 0. Two-way repeated ANOVA followed by the Student’s t-test with Bonferroni’s correction for multiple comparisons. SNL; spinal nerve ligation, 2W; 2week after SNL surgery, 6W; 6week after SNL surgery, AAV; adeno-associated virus, DREADD; designer receptor exclusively activated by designer drugs, AAV; adeno associated virus, CNO; clozapine N oxide, LC; locus coeruleus.