Figure 5. In humans, co-injection of β-alanine (ALA) and bovine adrenal medulla peptide 8–22 (BAM8-22) with or without histamine (HIS) does not change the itch or nociceptive sensations compared to the effects of one component pruritogen given alone.

(A) The majority of subjects (n = 29) reported itch, pricking/stinging, and burning sensations after administration of each of the pruritogens or their combinations. (B) Magnitude of itch, (C) stinging/pricking, and (D) burning sensations evoked by BAM8-22, ALA, and a combination of BAM8-22 and ALA are plotted for successive 30 s intervals after injection averaged across all 29 subjects. (E) Magnitude of itch, (F) stinging/pricking, and (G) burning sensations evoked by HIS, a combination of BAM8-22 and ALA, and a combination of BAM8-22, ALA, and HIS. For clarity, the standard error of the mean (SEM) is plotted only every 5 min starting with the peak rating for each quality. On the right vertical axis, the locations of three verbal descriptors are shown in correspondence with the ratings of perceived intensity indicated on the left vertical axis (see Materials and methods). (H) Peak magnitude of perceived sensation intensity (n = 29), (I) computed area under the curve (n = 17), or (J) duration of itch, stinging/pricking, or burn ratings (n = 17) were each not significantly different for the five different stimuli, that is, three single pruritogens and two combinations (repeated measures ANOVA [RMANOVA], see text for further details). For (I) and (J), subjects (n = 12) without a measurable area under the curve (AUC) or duration of any sensation during the time course were not included in the analysis, and therefore only 17 subjects were used for within-subjects analysis and post hoc comparisons. Data represent mean ± SEM.

Figure 5—figure supplement 1. In humans, co-injection of β-alanine (ALA) and bovine adrenal medulla peptide 8–22 (BAM8-22) with or without histamine (HIS) does not change the itch or nociceptive sensation compared to the effects of one of the component pruritogens given alone.

(A) Magnitude of itch, (B) AUC and (C) Duration of sensation. Data are plotted in the same format as Figure 5H–J for the 25 subjects that, in response to each single pruritogen, reported a greater than zero peak magnitude of both itch and either type of nociceptive sensation (whichever elicited the greater area under the curve [AUC]). This increased the sample size from n = 17 in Figure 5I, J to n = 25 by including the data for eight additional subjects that always felt at least one type of nociceptive sensation but not always both. A 5 ‘stimulus’ × 2 ‘sensory quality’ repeated measures ANOVA (RMANOVA) was performed for peak magnitude, AUC, and duration. For peak magnitude, only ‘stimulus’ had a significant effect (F_(4,96)=2.85, p<0.03) with BAM8-22 producing a higher peak magnitude of sensation than ALA (p<0.034, Bonferroni test). The interaction between ‘stimulus’ and ‘sensory quality’ was not significant (F_(4,96)=1.89, p=0.12). For AUC, only ‘sensory quality’ was significant (F_(1,24.0) = 5.25, p<0.032), with the mean AUC for itch being significantly larger than that for nociceptive sensation (p<0.032, Bonferroni test). The interaction between ‘stimulus’ and ‘sensory quality’ was not significant (F_(1.7,42.2) = 0.91, p=0.40). For duration, ‘stimulus’ and ‘sensory quality’ were each significant (F_{(2.75, 66.0)}=4.25, p=0.010 and F_(1,24.0) = 13.03, p=0.001, respectively), but their interaction was not (F_{(2.78, 66,8)}=2.1, p=0.11). HIS-induced sensations lasted significantly longer than those induced by ALA or by BAM8-22 + ALA (p<0.01 and p<0.05, respectively). Furthermore, the duration of itch was significantly greater than for the nociceptive sensation (p=0.001, Bonferroni test).