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Inhibition of c-Kit signaling is associated with reduced heat and cold pain sensitivity in humans

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Item Type:Article
Title:Inhibition of c-Kit signaling is associated with reduced heat and cold pain sensitivity in humans
Creators Name:Ceko, M. and Milenkovic, N. and Le Coutre, P. and Westermann, J. and Lewin, G.R.
Abstract:The tyrosine kinase receptor c-Kit is critically involved in the modulation of nociceptive sensitivity in mice. Ablation of the c-Kit gene results in hyposensitivity to thermal pain, while c-Kit activation produces hypersensitivity to the noxious heat, without altering sensitivity to innocuous mechanical stimuli. In this study we investigated the role of c-Kit signalling in human pain perception. We hypothesized that subjects treated with Imatinib or Nilotinib, potent inhibitors of tyrosine kinases including c-Kit, but also Abl1, PDFGFR{alpha}, and PDFGFR{beta}, that are used to treat chronic myeloid leukemia (CML), would experience changes in thermal pain sensitivity. We examined 31 asymptomatic CML patients (14 male, 17 female) under Imatinib/Nilotinib treatment and compared them to 39 age- and sex-matched healthy controls (12 male, 27 female). We used cutaneous heat and cold stimulation to test normal and noxious thermal sensitivity, and a grating orientation task to assess tactile acuity. Thermal pain thresholds were significantly increased in the Imatinib/Nilotinib-treated group, while innocuous thermal and tactile thresholds were unchanged compared to the control group. In conclusion, our findings suggest that the biological effects of c-Kit inhibition are comparable in mice and humans in that c-Kit activity is required to regulate thermal pain sensitivity, but does not affect innocuous thermal and mechanical sensation. The effect on experimental heat pain observed in our study is comparable to that of several common analgesics, thus modulation of the c-Kit pathway can be used to specifically modulate noxious heat and cold sensitivity in humans.
Keywords:Heat Pain, Cold Pain, C-Kit, Imatinib, Nilotinib, Tactile Acuity, Chronic Myeloid Leukemia, Analgesia, Quantitative Sensory Testing
Page Range:1222-1228
Date:July 2014
Official Publication:https://doi.org/10.1016/j.pain.2014.03.010
PubMed:View item in PubMed

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