Fig. 1
Role of Piezo2 in peripheral tissue in innocuous stimulus-induced enhancement of the mechanical hyperalgesia induced by endothelin-1. Rats received an intradermal injection of a combination of 3 sequences of ODN mismatch (MM, open symbols) or antisense (AS, dark symbols) against Piezo2 mRNA (20 μg of each sequence/μl, added to 2 μl of oligofectamine; total volume: 5 μl) on the dorsum of the hind paw. 6 h later, endothelin-1 (100 ng) was injected at the same site. At the same site, the paws then were submitted to 4 mechanical stimuli, 5 min apart from each other, starting 15 min after endothelin-1 injection. In the paws pretreated with local injection of ODN AS, compared to ODN MM, the decrease in the nociceptive threshold subsequent to the mechanical stimulations was significantly attenuated, indicating a role of peripheral Piezo2 channels in stimulus-dependent hyperalgesia. (F1,10 = 140.7; **p < 0.0061 and ****p < 0.0001, when the groups are compared at each reading, two-way repeated measures ANOVA followed by Bonferroni’s post hoc test; N = 6 paws per group). a Shows the mechanical nociceptive threshold, in grams, after each stimulation, starting 15 min post-endothelin-1 injection; in b, the reduction in the mechanical threshold after each stimulation, when compared to the baseline, is represented as percentage change