Abstract
Chronic pruritus is a symptom that commonly observed in neurological diseases. It has been hypothesized that the chronic pruritus may result from sensitization of itch-signaling pathways but the mechanisms remain obscure. In this study, we established a mouse model of chronic compression of dorsal root ganglion (CCD) and injected various pruritogenic and algogenic agents intradermally to the calf skin ipsilateral to the compressed dorsal root ganglion (DRG). Compared to the naïve mice, a significant increase in itch-related behaviors was observed in the CCD mice after the injection of pruritogens including histamine and BAM8-22, but not after the injection of capsaicin, although all the above agents evoked enhanced pain-related behaviors toward the injected site. In addition, we investigated if pruritogen-evoked activities of DRG neurons were enhanced in this model. In vivo calcium imaging revealed that compressed DRG neurons exhibited enhanced responses to histamine and BAM8-22. Immunoflorescent staining also showed that the histamine receptor H1 and the capsaicin receptor TRPV1 were significantly upregulated in DRG neurons. Our findings indicated that the sensitization of primary pruriceptive neurons may underlie the enhanced itch sensation after chronic compression of DRG in the mice, and may play a role in chronic pruritus in neurological diseases.
Highlights
Itching has been defined as an “unpleasant skin sensation that elicits the desire or reflex to scratch’’ [1]
Sensitized dorsal root ganglia (DRG) neurons show enhanced response to chemical stimuli after chronic compression of dorsal root ganglion (CCD) To explore the behavioral effects of TRPV1, Histamine, and MrgprA3 receptor activation after CCD, we used a calf model that allows differentiation of side-directed itch- and pain-like behaviors in response to pruritic and algesic chemical stimuli
These results indicate that CCD caused a sensitization of capsaicinevoked pain, but not cause a sensitization of capsaicinevoked itch
Summary
Itching (pruritus) has been defined as an “unpleasant skin sensation that elicits the desire or reflex to scratch’’ [1]. Primary sensory neurons in dorsal root ganglia (DRG) play an important role in generating itch by detecting pruritogenic stimuli via their peripheral axons in the skin and sending the signals to the spinal cord through their central axons [2]. Itch and pain are both somatosensory sensations achieved by activating sensory nerves, they can be differentiated by psychophysiological. Chronic compression of the dorsal root ganglion (CCD) is a preclinical model of lumbar intraforaminal stenosis and radicular pain [5, 6]. The cell bodies of sensory neurons in the compressed DRG become hyperexcitable as evidenced by the presence of spontaneous activity originating in the DRG [12, 13], and elevated responses to electrical, thermal, and chemical nociceptive stimuli [14].
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