Introduction: 

High-frequency electrical stimulation (HFS) of nociceptive afferents leads to long-lasting enhancement of pain perception in humans (perceptual correlates of spinal nociceptive long-term potentiation, pain-LTP; Klein et al. 2004). Here we tested the relative contribution of a specific subset of nociceptors bearing the TRPV1-(Capsaicin-) receptor in the induction of pain-LTP.

Method: 

Capsaicin (8%, Qutenza®) and placebo plasters were delivered to the forearm skin for 2x22h in 21 male (age 24±4y/o) in a cross-over design to elicit a transient denervation of TRPV1-pos. afferents in the skin. Desensitization was monitored by determination of heat pain thresholds (HPT). Pain-LTP was induced at both skin sites by HFS (5x1s at 100Hz at 10x detection threshold) 24h after removing the plaster. Pain to single electrical test stimuli applied via the conditioning electrode (homotopic pain-LTP) as well as to mechanical pinprick stimuli (8–512mN) adjacent to the conditioned area (heterotopic pain-LTP) were estimated by means of a numerical rating scale (0–100).

Results: 

HPT increased from to 45.4±2.1°C at baseline nearly to cut off temperature of 50°C (49.9±0.4°C (p<0.001) in the capsaicin treated skin, whereas it decreased from 45.8±2.6to 44.5±2.2°C (p<0.01) at the control site. Pain to conditioning HFS in desensitized vs. naïve skin was reduced by 53% (16.5 vs. 34.9/100). Homotopic (+40% vs. 142% vs. baseline) as well as heterotopic pain-LTP (+11% vs. 134% vs. baseline; both p<0.001) in capsaicin-treated skin were significantly reduced compared to control pain-LTP.

Conclusion: 

The loss of heat sensitivity in the capsaicin treated skin suggests a nearly complete loss of TRPV1-positive afferents in the skin. The strong reduction of pain-LTP indicates the importance of heat-sensitive, TRPV1-R positive afferents in the induction of LTP-like enhancement of pain perception in humans.