Figure 7
Intradermal injections of ATX-II induces pain and an itch-like sensations in human volunteers. (a) Pain assessment (on a numerical rating scale, NRS 0–10) as a function of time for a subject following injection of saline solution without (control) or with ATX-II. Under control conditions (white symbols) only a short lasting pain is evoked immediately after the injection in agreement with mechanical irritation, whereas ATX-II injection (blue symbols) leads to distinctly augmented ratings. The right panel shows the mean area under the curve (AUC) for n = 6 volunteers (* p < 0.05). (b) Assessment of itch-like sensations on a NRS ranging from 0–10 following injection (sensation rated as 3 is equivalent to desire to scratch) of one representative subject. While under control conditions (white symbols) no itch is induced following injection, ATX-II (red symbols) evoked itch-like sensations, also reflected in a larger AUC (right, * p < 0.05). (c) and (d) Pain (blue squares and bar) and itch (red squares and bar) ratings as a function of time following compression induced nerve block. After 30–40 min of A-fiber block ATX-II was injected and sensations were rated during 10 min (hatched squares). While no pain and itch is evoked by ATX-II under nerve block conditions, pain (blue symbols) and itch (red symbols) recur fast after removal of the block. AUCs of pain ratings increased significantly after removal of the block (* p < 0.05). (e) Area of increased blood flow measured by laser doppler imaging every 2 min following ATX-II injection (blue squares, n = 6) shows hardly any increase in superficial blood flow. For comparison, a typical histamine-induced axon reflex erythema mediated by activation of C-fibers and concomitant CGRP release is shown (white squares). Right: Example images taken 4 min after application of substances. (f) Assessment of cold-evoked (0°C, 7 s) pain (NRS 0–10) before (white bar) and during nerve block (hatched bars). 10 min after injection of ATX-II cold-evoked pain is rated and the nerve block removed. Cold-evoked pain 20 and 30 min after injection of ATX-II significantly increases following removal of the nerve block (* p < 0.05).