Background & Aims
Ketamine, 2-(2-chlorophenyl)-2-(methylamino)-cyclohexanone is an antagonist of glutamate N-methyl-D-aspartate (NMDA) receptors 1. NMDA receptors are widely present not only in the central nervous system but also in peripheral nerves 2. In the clinical setting, topical ketamine cream has been successfully used to relieve various pathogenic forms of pain 3. The cream was also reported to have itch-relieving properties in a very limited study 4. However, its efficacy on itch has not been established, and the mechanism of action remains uncertain.
This pilot study aimed to evaluate the effect of ketamine cream (ketamine 0.5%, amitriptyline 1%) on histaminergic and non-histaminergic itch induced by histamine and cowhage, respectively.
Methods
Ten healthy subjects were recruited in this pilot study. Four areas on the forearms were treated as follows: histamine (1%, in saline), cowhage, ketamine+histamine, and ketamine+cowhage. Ketamine cream was applied for 1½ hours under occlusion. After the application of pruritogens, itch intensity was assessed with a visual analogue scale (VAS) for 9 minutes, followed by the measurement of superficial blood perfusion (SBP) by full-field laser perfusion imaging (FLPI). From VAS data, peak, area under the curve (AUC), and the temporal profile of itch perception have been extracted. From FLPI data, mean and peak of SBP, and the flare area have been extracted.
Results
Ketamine reduced the peak itch intensity induced by cowhage (p<0.01), without affecting the histamine-induced itch (p=0.209). For the AUC (area under the curve), it is possible to see only a tendency (p=0.09). Ketamine reduced both the mean of SBP and the flare area (p<0.05), while only a tendency for reduction was present for the peak of SBP (p=0.068). Concerning the mean of SBP, ketamine reduced the mean induced by histamine (p<0.01), without affecting the cowhage-induced mean SBP (p=0.357). On the other hand, ketamine reduced the flare area size induced by both histamine and cowhage (p<0.05).
Conclusions
This pilot study confirmed the antipruritic and anti-neurogenic inflammatory effect of ketamine cream on histaminergic and non-histaminergic pathways. More studies are needed to clarify its mechanism of action.
References
1.Alkire, M. T., Hudetz, A. G. & Tononi, G. Consciousness and anesthesia. Science (1979) 322, 876–880 (2008).
2.Carlton, S. M. Peripheral NMDA receptors revisited–Hope floats. Pain 146, 1–2 (2009).
3.Kopsky, D. J. et al. Analgesic effects of topical ketamine. Minerva Anestesiol 81, 440–449 (2015).
4.Mirzoyev, S. A. & Davis, M. D. P. Brachioradial pruritus: Mayo Clinic experience over the past decade. British Journal of Dermatology 169, 1007–1015 (2013).
Presenting Author
Silvia Lo Vecchio
Poster Authors
Topics
- Specific Pain Conditions/Pain in Specific Populations: Itch