Intradermal Capsaicin Causes Dose-Dependent Pain,Allodynia,and Hyperalgesia in Humans

Abstract

Background

Intradermal capsaicin is a human pain model that produces reliable pain and sensitization. This model facilitates controlled testing of analgesic efficacy via a crossover design while minimizing confounding variables in clinical pain states and retaining sufficient power with small samples.

Methods

To determine the lowest dose of capsaicin that produces consistent neurosensory measures, we administered 0.1, 1, 10, or 100 μg to healthy volunteers in a blinded manner (N = 19). Pain scores were recorded at 0, 5, 10, 15, and 60 minutes on a visual analog scale from 0 to 100. Areas and intensities of mechanical allodynia (foam brush stimulus) and pinprick hyperalgesia (von Frey test) were quantified at 15 and 60 minutes, as were flare areas.

Results

Capsaicin produced dose-dependent increases in spontaneous pain (p = .013), the area and intensity of mechanical allodynia (p = .006 and p < .001, respectively), the area and intensity of pinprick hyperalgesia (p = .010 and p = .014, respectively), and the flare area (p = .010). The 10 μg dose produced greater spontaneous pain than the 1 μg dose (p = .017). The 100 μg dose produced greater spontaneous pain than the 10 μg, but the difference was not statistically significant.

Conclusion

The 10 and 100 μg capsaicin doses produced robust pain measures across a range of modalities, and lower doses produced minimal effects. Whereas most studies use 100 μg, using a lower dose is reasonable and may facilitate detection of subtle analgesic effects—particularly with nonopioid analgesics—and drugs can be tested in lower doses, minimizing adverse side effects.