Intradermal glutamate and capsaicin injections: Intra‐ and interindividual variability of provoked hyperalgesia and allodynia

Abstract

Intradermal injections of glutamate and capsaicin are attractive to use in human experimental pain models because hyperalgesia and allodynia mimic isolated aspects of clinical pain disorders. The aim of the present study was to investigate the reproducibility of these models. Twenty healthy male volunteers (mean age 24 years; range 18-38 years) received intradermal injections of glutamate and capsaicin in the volar forearm. Magnitudes of secondary pinprick hyperalgesia and brush-evoked allodynia were investigated using von Frey filaments (gauges 10, 15, 60 and 100 g) and brush strokes. Areas of secondary hyperalgesia and allodynia were quantified immediately after injection and after 15, 30 and 60 min. Two identical experiments separated by at least 7 days were performed. Reproducibility across and within volunteers (inter- and intra-individual variation, respectively) was assessed using intraclass correlation coefficient (ICC) and coefficient of variation (CV). Secondary pinprick hyperalgesia was observed as a marked increase in the visual analogue scale (VAS) response to von Frey gauges 60 and 100 g (P < 0.001) after glutamate injection. For capsaicin, secondary pinprick hyperalgesia was detected with all von Frey gauges (P < 0.001). Glutamate evoked reproducible VAS response to all von Frey gauges (ICC > 0.60) and brush strokes (ICC > 0.83). Capsaicin injection was reproducible for secondary hyperalgesia (ICC > 0.70) and allodynia (ICC > 0.71). Intra-individual variability was generally lower for the VAS response to von Frey and brush compared with areas of secondary hyperalgesia and allodynia. In conclusion, glutamate and capsaicin yield reproducible hyperalgesic and allodynic responses, and the present model is well suited for basic research, as well as for assessing the modulation of central phenomena.

Inflammatory pain models with capsaicin or glutamate injections: Are they comparable and reproducible?

“…A total of 20 healthy male volunteers were subjected to intradermal injections of glutamate and capsaicin in the forearm. The study by Nilsson et al . shows that both capsaicin and glutamate produce allodynia or/and hyperalgesia in these human subjects.…”

“…Thus, similar to capsaicin, intradermal administration of glutamate would induce secondary hyperalgesia and allodynia in human clinical settings . A major concern if inflammatory substances cause hyperalgesia and allodynia is the reproducibility of preclinical and clinical observations.…”

“…A major concern if inflammatory substances cause hyperalgesia and allodynia is the reproducibility of preclinical and clinical observations. Several investigators reported variability in the response to intradermal and topical capsaicin that could be due to subject numbers and/or variability attributed to non‐responders . Furthermore, although the capsaicin model is frequently used in pharmacological profiling of novel analgesic compounds, direct comparison between capsaicin and glutamate in causing hyperalgesia and allodynia would be desirable …”

“…In this issue of CEPP, Nilsson et al . report the comparison and reproducibility of capsaicin and glutamate in healthy humans.…”

“…It should be noted though that the level of hyperalgesia induced by glutamate was moderate, meaning only visible with the filaments of 60 g or more. The magnitudes of secondary pinprick hyperalgesia and brush‐evoked allodynia were investigated using von Frey filaments and brush strokes . The reproducibility across volunteers and within volunteers was assessed using the intraclass correlation coefficient and coefficient of variation, as well as the visual analogue scale, for assessment of secondary pinprick hyperalgesia after glutamate or capsaicin injections .…”