Assessment of the reproducibility of intradermal administration of capsaicin as a model for inducing human pain

Abstract

The reproducibility and tolerability of intradermal (i.d.) administration of capsaicin as a method for eliciting human pain was assessed in healthy male volunteers (n = 12). The primary endpoints for assessing pain were spontaneous pain response and areas of allodynia, pinprick hyperalgesia and neurogenic inflammation. These were recorded before, immediately after, and at regular intervals following each of four doses (250 microg) of capsaicin (two per trial day). Within- and between-subject variability to the technique was assessed by measuring the maximum recorded values (max), time to maximum value (t(max)) and area under the curve (AUC(0-1 h)) of each of the endpoints. Tolerability to the technique was addressed by recording adverse events. Reproducibility of the i.d. capsaicin model was demonstrated for each type of capsaicin-induced pain. Following each dose, the magnitude and profile of response and overall AUC values were similar for each parameter although some decrease in pinprick hyperalgesia was observed over time. For spontaneous pain, evidence of a period effect was observed in mean AUC data, with values increasing following the second dose of each trial day. This effect was confounded by the possibility of an arm effect, with the non-dominant arm appearing to be more sensitive to pain than the dominant arm. The data were not sufficient to confirm the existence of these effects. Between-subject variability and within-day, within-subject variability accounted for most of the variability observed in the trial. By optimising study design to eliminate these sources of variability, it was estimated that spontaneous pain and the area of allodynia would be the least variable endpoints. A positive correlation was found between the area of allodynia and area of pinprick hyperalgesia (r(2) = 0.835). Overall, the model was well tolerated with no reports of adverse events. We conclude that the tolerability profile, and variability of i.d. capsaicin-induced pain is acceptable for pharmacological profiling of novel anti-nociceptive agents, with limited number of subjects.

Validation of the Simplified UVB Model to Assess the Pharmacodynamics of Analgesics in Healthy Human Volunteers

“…The variability observed for the UVB model was considerably smaller than that for the intradermal capsaicin model, in which the intra-and inter-individual variability was 140 and 787%, respectively. [22] Hyperalgesia to mechanical stimuli was still present in both zones 44 h after UVB exposure (MPT = 72.4 ± 53.0 g and 134.6 ± 61.7 g, respectively). Fig.…”

Esophageal Submucosal Injection of Capsaicin but Not Acid Induces Symptoms in Normal Subjects

“…23,24 Capsaicin is a specific agonist of TRPV1 and has been extensively used to study the mechanism of somatic pain (intradermal junction). 13,14 While the strength of a human experiment, like ours, is that it allows qualitative and quantitative assessment of pain, it does not allow detailed study of the molecular mechanism. For example, we could not assess if the mechanism of action of capsaicin in our experiment is specifically through TRPV1 receptors because there is no TRPV1 antagonist available for human use.…”

“…The selected capsaicin dose was based on prior studies that utilized intradermal capsaicin injection. 13,14 Single injections of 0.1 mL of vehicle and capsaicin (vehicle always first) were made 5 cm above the Z line. Following injections, subjects reported the location, severity and quality of symptoms, every 2 minutes for 30 minutes using the McGill Pain Questionnaire.…”

Unravelling the Mystery of Capsaicin: A Tool to Understand and Treat Pain

“…This is independent of the mechanism involved in temporal summation, which affects only the same synaptic input that has transmitted the intense stimulus, indicating homosynaptic facilitation. Intradermal capsaicin administration in humans has been investigated regarding reliability, reproducibility, and sensitization, and analysis of underlying mechanisms has been extensive (Hughes et al, 2002). Scanlon et al (2006) investigated capsaicin-induced spontaneous pain corresponding to C-fiber activity, pin-prick hyperalgesia (quantified and evoked by use of e.g., von Frey filaments), which is mediated by Cand A␦-fibers, and finally allodynia (evoked by gentle brush stimulation) primarily mediated by A␤-fibers.…”

“…However, it is crucial that the dose of capsaicin produces consistent neurosensory measures. In addition, use of 100 g has shown to be reproducible and valid over time, important factors in clinical studies investigating mechanisms and effects of analgesics and antihyperalgesics (Simone et al, 1989;Hughes et al, 2002).…”