Specific Patterns of Spinal Metabolite Ratio Underlying α-Me-5-HT-evoked Pruritus Compared with Compound 48/80 Based on Proton Nuclear Magnetic Resonance Spectroscopy

Abstract

Mechanisms of pruritus are implicated in the dysregulation of the metabolites in the spinal cord. We investigated pruritus behavioral testing in three groups of young adult male C57Bl/6 mice, including one group treated with normal saline, while the other groups intradermally injected with α-Me-5-HT (histamine-independent pruritogen), compound 48/80 (histaminedependent pruritogen) at the nape skin of the neck, respectively. Proton nuclear magnetic resonance spectroscopy (MRS) was used to compare spinal metabolites from the vertebral cervical among three groups, and to study the association of spinal metabolite ratio and pruritus intensity. The MRS-measured N-acetylaspartate-to-myoinositol ratio (NAA/Ins) was significantly correlated with the number of scratches between normal saline group and 48/80 group or α-Me-5-HT group (both P<0.0001), indicating that NAA/Ins may be a robust surrogate marker of histamine-independent/ dependent pruritogen. There was significant difference in Glu/Ins between normal saline group and 48/80 group (P=0.017), indicating that Glu/Ins may be a surrogate marker of histamine-dependent pruritogen, while GABA/Ins was highly significantly different between normal saline group and α-Me-5-HT group (P=0.008), suggesting that GABA/Ins may be a surrogate marker of histamineindependent pruritogen. MRS may reflect the extent of pruritus intensity elicited by α-Me-5-HT and compound 48/80 with sensitivity similar to the number of scratches, and above potential markers need to be further validated in pre-clinical and clinical treatment trials.

The Role of Gut Microbiota in Chronic Itch-Evoked Novel Object Recognition-Related Cognitive Dysfunction in Mice

“…The scratching behaviors were video-recorded through a transparent glass under the plastic chamber in the absence of any observer for 30 min. According to our previous research (5,6,9,25,26), a scratching bout is defined as lifting a hind paw toward the shaved region and returning the hind paw back to the floor or mouth for licking (27). Analyses of the videotapes were carried out in a blinded manner.…”

“…Similar to pain, itching is classified into two forms. Acute itching is easily reduced by scratching or antiallergic drugs whereas chronic repetitive itching remains a challenge to clinic cure (4)(5)(6)(7). It has been reported that the itch-scratch cycle plays an important role in the maintenance of the chronic itch (8)(9)(10)(11).…”