Fig. 2. Opioid agonist-induced inhibition of C-fiber mechanosensitivity following hypertonicity. (A–D ) Rats were intraplantarly injected with 10% NaCl or 0.9% NaCl, and skin nerve preparations were established. (A ) Mechanically evoked responses of C-fibers from 10% NaCl injected (n = 27) rat skin were not different from 0.9% NaCl (n = 19) injected paw. (B–D ) Responses of C-mechanonociceptors to a suprathreshold mechanical stimulus were recorded following exposure to synthetic interstitial fluid (SIF) (red squares ) or [d-Ala2,N-Me-Phe4,Gly5-ol]enkephalin (DAMGO) in SIF (10 μM, blue squares ). (B ) DAMGO had no effects on C-fiber responses when applied to receptive fields of 0.9% NaCl-injected paws (DAMGO, n = 18; SIF, n = 19). (C ) DAMGO significantly reduced the mechanically evoked responses of C-fibers in 10% NaCl-injected paws (*P < 0.05; repeated-measures ANOVA, Bonferroni post hoc correction; DAMGO, n = 17; SIF, n = 27). (D ) Coapplication of equimolar concentrations of DAMGO with a μ-opioid receptor-selective antagonist (D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2,CTOP 10 μM) reversed the DAMGO effect (blue circle ; SIF: red square , both n = 9; repeated-measures ANOVA, Bonferroni post hoc correction, P > 0.05). SIF = synthetic interstitial fluid.