Atopic eczema (AE) is a chronically pruritic inflammatory
skin disease. Although the mediators and exact mechanisms eliciting and sustaining
pruritus are not completely known, AE patients in clinical trials have been shown to benefit under treatment with
morphine antagonists.
Naltrexone (NAL) is a relatively pure
morphine antagonist that blocks the effects of
opioids twice as much as
naloxone. NAL exhibits minimal pharmacological activity and displaces endorphines at mu- and
kappa-receptors without its own intrinsic activity. NAL's excellent oral bioavailability and linear increases in the area under plasma concentration-time curve make it ideal for use in experimental studies. We designed our present experiments similar to former experiments evaluating both peripheral cutaneous sensations and central itch procession in order to gain more information about the possible distribution of
opioid receptors and their involvement in the pathophysiology of
pruritus. Eleven AE patients participated in our double-blind study. Either 25 mg of NAL (
Nemexin) or a placebo (PLA) was given to the participants 60 min prior to the
acetylcholine (ACH) injection [intracutaneous (i.c.) injection of 0.02 ml of 0.55 M]. A PLA stimulus with buffered saline served as control on the opposite forearm. We used
laser Doppler flowmetry to measure the vasomotoric changes after ACH injection and recorded the duration and intensity of itch with a visual analogue scale (VAS). Following the evaluation of wheal and flare sensation, we obtained the area of itchy skin around the injection site (alloknesis) by gently stroking the surrounding skin with a brush in the centripetal direction towards the injection site. The results were planimetrically evaluated. Oral NAL reduced the perifocal itch significantly (P < 0.009). In four of our observations the area of alloknesis completely disappeared. Itch duration was reduced by 20 s and the intensity of itch was diminished, yet not significantly. NAL had no significant effects on
cholinergic vasoreactions measured by the
laser Doppler (P > 0.50) and especially failed to decrease the initial flux response, which is a typical sign of an altered vascular reaction (P > 0.25). The decrease of wheal (P = 0.008) and flare (P = 0.01) extension indicates an appropriate dosage of our treatment for this experiment. The most significant effects of NAL were observed in parameters of itch processing such as alloknesis (P = 0.009) and flare extension (P = 0.01). Therefore we favour the concept that NAL might have a stronger impact on central nervous mechanisms than on peripheral nociceptive structures.