Table 1.

Human studies using intradermal capsaicin

Amount/Test Devices	Method	Results	Reference
250 μg Artist's Number 2 brush (1 cm/s from a point 10 cm away); Von Frey hair (microfilament bending threshold 196 mN at a point 10 cm away)	Capsaicin was injected intradermally in the left and right arm of 12 healthy male volunteers. Spontaneous pain response and areas of allodynia and hyperalgesia were measured.	Little variability in pain perception and allodynia was observed. With each subsequent injection, variability was observed for pinprick hyperalgesia The nondominant arm might be more sensitive to pain than the dominant arm.	Hughes et al. (2002)
0.05, 1, and 20 μg	Injection was performed across three sessions 1 week apart. Pain ratings were recorded immediately or 1 h or 1 day after injection. Subjects recalled their pain 1 week later.	The strong burning pain of the injection declined within a few minutes. Subjects were able to reliably discriminate pain magnitude and duration. This was also the case for pain recall.	Jantsch et al. (2009)
10 μg Nylon filament (225 mN)	Microelectrodes were inserted in the peroneal nerve just below the knee, measuring the nerve activity after capsaicin injection. Pain intensity to each stimulus was assessed. Spontaneous pain to injection of capsaicin was recorded for the first 3 min. Pinprick hyperalgesia was measured.	Intradermal application close to or inside the receptive field led to higher discharge rates. Discharge rates decreased by mechanical stimulation. Pain was positively correlated to high discharge rates. Activity in C mechano-heat nociceptors contributed to the magnitude and duration of pain evoked by intradermal injection of capsaicin. After-effects were concentration related: high concentration led to desensitization, low concentration led to sensitization.	LaMotte et al. (1992)
250 μg	Capsaicin was injected in the volar forearm and dorsal foot. Temperature was fixed or varied followed by observation of pinprick hyperalgesia and brush stroke. Skin blood flow was measured.	Stabilized skin temperature before injection decreased variability. A lower concentration of capsaicin injected in the forearm led to a decreased between-session consistency. The dorsal foot was more sensitive than the volar forearm. Blood flow in the dorsal foot increased with reclining position.	Liu et al. (1998)
10–25 of 10 mg/ml Semmes-Weinstein monofilament (26g)	Capsaicin was injected in the forearm or thigh. Spontaneous pain intensity was recorded at time of injection and every 5 min up to 20 min. Area of hyperalgesia was assessed.	Spontaneous pain intensity declined over time. A persistent area of secondary tactile allodynia was observed.	Modir and Wallace (2010)
50 μg Von Frey filament (60g)	14 Healthy volunteers (9 men, 5 women) were tested for in regions of the forearm: cold stimuli (30, 20, 10, and 0°C) by a squared contact thermode before and after capsaicin injection. Hyperalgesia after an intradermal capsaicin injection by testing with punctuate stimuli (von Frey filament). Skin blood flow (laser Doppler flowmetry) and temperature (infrared camera) were measured before and after capsaicin injection.	Increase in blood flow after baseline cold stimulation at the 0°C compared with the three other sides. In addition, vasodilatory effect was found after the capsaicin injection compared with baseline for all regions.	Pud et al. (2005)
0.1, 1, 10, or 100 μg	Pain scores were recorded 0, 5, 10, 15, and 60 min after injection. Areas of mechanical allodynia and pinprick hyperalgesia were quantified 15 and 60 min after injection.	Capsaicin produced dose-dependent increases in spontaneous pain, the area of mechanical allodynia, the area of pinprick hyperalgesia, and visual flare. 10 μg produced significantly more pain than 1 μg. 100 μg produced more pain than 10 μg, but not significantly.	Scanlon et al. (2006)
0.1–100 μg	Capsaicin injection into the forearm. Pain threshold to heat and hyperalgesia was assessed.	Heat pain threshold was lowered in the injection site. Magnitude and duration of hyperalgesia was dose dependent.	Simone et al. (1987)
250 μg	Capsaicin-evoked pain intensity was assessed every 1 min for 5 min and every 5 min the following 30 min. 5, 30 and 60 min after injection, temperature and blood flow were measured, followed by assessment of visual flare and hyperalgesia. Secondary hyperalgesia, stroking (cotton swab) and heat was assessed.	Blood flow and temperature increased after injection. Areas of visual flare, stroking hyperalgesia, and punctuate hyperalgesia were covered by the area of significantly increased bloodflow detected 5 min after injection. There was no difference in pain intensity to radiant heat inside/outside the area of punctuate hyperalgesia	Sumikura et al. (2003)
10 μg	Spontaneous pain and secondary mechanical hyperalgesia was assessed after injection. Melittin injection (a main compound of bee venom) was compared to injection of capsaicin.	Capsaicin and melittin evoked comparable spontaneous pain. Larger areas of mechanical hyperalgesia was observed after injection of capsaicin compared with melittin.	Sumikura et al. (2003)
10 μg 0.5–1.5 cm soft hair brushes	Capsaicin was injected in the volar part of the nondominant arm. Continuously perceived pain was assessed. Heterotopic stimulation with cold water that was nonpainful or painful (induction of diffuse noxious inhibitory control) was applied to the foot. Experiment 1, continuous brush-evoked pain intensity was scored together with capsaicin injection Experiment 2, continuous brush-evoked pain intensity was scored alone.	Immersion of the foot into cold water reduced capsaicin-evoked pain intensity and brush evoked pain but not the area of brush-evoked pain.	Witting et al. (1998)
10 μg Brush (0.7 cm/s and 0.15–0.20 N/cm2) and von Frey size (75, 86 g)	Capsaicin was injected intradermally in the volar part of the forearm in 17 healthy volunteers. Injections: 7–8 cm proximal from the wrist at four sites as a square. Experiment 1, 6-, 15-, or 24- min intervals Experiment 2, distance of 0.5 or 4 cm Pain intensity and areas of allodynia and hyperalgesia were measured.	The response to intradermal injection of capsaicin was dependent on time and distance between injections. Lack of significant relation between capsaicin pain intensity, area of allodynia. and hyperalgesia suggest different central mechanism.	Witting et al. (2000)
40 μg 200-μm diameter probes (35–407 nM)	Blockade of the superficial radial nerve, followed by capsaicin injection. Secondary hyperalgesia was detected by pinprick.	Pricking pain by punctuate stimuli was reduced by 75%, when A-fiber were fully blocked but with fully intact C-fiber. Burning pain to capsaicin injection remained unchanged. Hyperalgesia to punctuate stimuli was detectable immediately after block release, when A-fiber conduction returned to normal.	Ziegler et al. (1999)