Summary
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 (histamine-dependent 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 histamine-independent 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.
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References
Meixiong J, Anderson M, Limjunyawong N, et al. Activation of Mast-Cell-Expressed Mas-Related G-Protein-Coupled Receptors Drives Non-histaminergic Itch. Immunity, 2019,50(5):1163–1171
Meixiong J, Vasavda C, Green D, et al. Identification of a bilirubin receptor that may mediate a component of cholestatic itch. Elife, 2019,8:e44116
Yosipovitch G, Reaney M, Mastey V, et al. Peak Pruritus Numerical Rating Scale: psychometric validation and responder definition for assessing itch in moderate-to-severe atopic dermatitis. Br J Dermatol, 2019,181(4):761–769
Liu BW, Li ZX, He ZG, et al. Altered expression of itch-related mediators in the lower cervical spinal cord in mouse models of two types of chronic itch. Int J Mol Med, 2019,44(3):835–846
Chen M, Li ZX, Wang Q, et al. Altered Expression of Differential Genes in Thoracic Spinal Cord Involved in Experimental Cholestatic Itch Mouse Model. Curr Med Sci, 2018,38(4):679–683
Wang Q, Li ZX, Liu BW, et al. Altered expression of differential gene and lncRNA in the lower thoracic spinal cord on different time courses of experimental obstructive jaundice model accompanied with altered peripheral nociception in rats. Oncotarget, 2017,8(62):106 098–106 112
Liu T, He Z, Tian X, et al. Specific patterns of spinal metabolites underlying alpha-Me-5-HT-evoked pruritus compared with histamine and capsaicin assessed by proton nuclear magnetic resonance spectroscopy. Biochim Biophys Acta, 2017,1863(6):1222–1230
Liu BW, Li ZX, He ZG, et al. Altered expression of target genes of spinal cord in different itch models compared with capsaicin assessed by RT-qPCR validation. Oncotarget, 2017,8(43):74 423–74 433
Liu T, Li Z, He J, et al. Regional Metabolic Patterns of Abnormal Postoperative Behavioral Performance in Aged Mice Assessed by (1)H-NMR Dynamic Mapping Method. Neurosci Bull, 2020,36(1):25–38
Wang J, Zeng HL, Du H, et al. Evaluation of metabolites extraction strategies for identifying different brain regions and their relationship with alcohol preference and gender difference using NMR metabolomics. Talanta, 2018,179(1):369–376
Malatji BG, Meyer H, Mason S, et al. A diagnostic biomarker profile for fibromyalgia syndrome based on an NMR metabolomics study of selected patients and controls. BMC Neurol, 2017,17(1):88
de Graaf RA, Chowdhury GM, Behar KL. Quantification of high-resolution (1)H-[(1)(3)C] NMR spectra from rat brain extracts. Anal Chem, 2014,86(10):5032–5038
Guan M, Xie L, Diao C, et al. Systemic perturbations of key metabolites in diabetic rats during the evolution of diabetes studied by urine metabonomics. PLoS One, 2013,8(4):e60409
de Graaf RA, Chowdhury GM, Behar KL. Quantification of high-resolution (1)H NMR spectra from rat brain extracts. Anal Chem, 2011,83(1):216–224
Widerstrom-Noga E, Pattany PM, Cruz-Almeida Y, et al. Metabolite concentrations in the anterior cingulate cortex predict high neuropathic pain impact after spinal cord injury. Pain, 2013,154(2):204–212
Sun YG, Zhao ZQ, Meng XL, et al. Cellular basis of itch sensation. Science, 2009,325(5947):1531–1534
Sun YG, Chen ZF. A gastrin-releasing peptide receptor mediates the itch sensation in the spinal cord. Nature, 2007,448(7154):700–703
Song Y, Pan X, Liu C, et al. Role of nociceptive arcuate nucleus neurons in chloroquine-induced pruritic behaviors in mice. J Huazhong Univ Sci Technolog Med Sci, 2012,32(6):919–922
Liu C, Liu TT, He ZG, et al. Inhibition of itch-related responses by selectively ablated serotonergic signals at the rostral ventromedial medulla in mice. Int J Clin Exp Pathol, 2014,7(12):8917–8921
He ZG, Liu BW, Li ZX, et al. Altered expression profiling of spinal genes modulated by compound 48/80 in a mouse itch model. J Anesth Perioperat Med, 2017,4(5):220–224
Zeng HL, Yu FL, Zhang Z, et al. Quantitative proteomics study of host response to virulent and attenuated pseudorabies virus infection in mouse brain. Biochim Biophys Acta Proteins Proteom, 2018,1866(2):307–315
Wang SJ, Lirng JF, Fuh JL, et al. Reduction in hypothalamic 1H-MRS metabolite ratios in patients with cluster headache. J Neurol Neurosurg Psychiatry, 2006,77(5):622–625
Duan B, Cheng L, Ma Q. Spinal Circuits Transmitting Mechanical Pain and Itch. Neurosci Bull, 2018,34(1):186–193
Patti GJ, Yanes O, Shriver LP, et al. Metabolomics implicates altered sphingolipids in chronic pain of neuropathic origin. Nat Chem Biol, 2012,8(3):232–234
Johnson CH, Patti GJ, Courade JP, et al. Alterations in Spinal Cord Metabolism during Treatment of Neuropathic Pain. J Neuroimmune Pharmacol, 2015,10(3):396–401
Ma Q. Itch Modulation by VGLUT2-Dependent Glutamate Release from Somatic Sensory Neurons. In: Carstens E, Akiyama T, editors. Itch: Mechanisms and Treatment. Boca Raton (FL), 2014.
Bourane S, Duan B, Koch SC, et al. Gate control of mechanical itch by a subpopulation of spinal cord interneurons. Science, 2015,350(6260):550–554
Liu T, Han Q, Chen G, et al. Toll-like receptor 4 contributes to chronic itch, alloknesis, and spinal astrocyte activation in male mice. Pain, 2016,157(4):806–817
Jing PB, Cao DL, Li SS, et al. Chemokine Receptor CXCR3 in the Spinal Cord Contributes to Chronic Itch in Mice. Neurosci Bull, 2018,34(1):54–63
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This work was supported by grants from the National Natural Science Foundation of China (No. 81670240 and No. 81873467) and the Medical Innovation Project in Fujian Province (No. 2017-CX-48).
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Chen, Yl., He, Zg., Wang, Q. et al. 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. CURR MED SCI 40, 761–766 (2020). https://doi.org/10.1007/s11596-020-2233-x
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DOI: https://doi.org/10.1007/s11596-020-2233-x