Systematic Administration of B Vitamins Alleviates Diabetic Pain and Inhibits Associated Expression of P2X3 and TRPV1 in Dorsal Root Ganglion Neurons and Proinflammatory Cytokines in Spinal Cord in Rats

Overview

Journal Pain Res Manag

Date 2020 Feb 28

PMID 32104520

Citations 5

Authors

Duan-Duan He

Yu Gao

Shan Wang

Zhong Xie

Xue-Jun Song

Affiliations

Soon will be listed here.

Abstract

Background: Treatment of diabetic neuropathic pain (DNP) continues to be a major challenge, and underlying mechanisms of DNP remain elusive. We investigated treatment effects of B vitamins on DPN- and DNP-associated alterations of neurochemical signaling in the nociceptive dorsal root ganglion (DRG) neurons and the spinal cord in rats.

Methods: DNP was produced in male, adult, Sprague Dawley rats by single i.p. streptozotocin (STZ). Western blot analysis and immunohistochemistry were used to analyze protein expressions in DRG and ELISA to measure the proinflammatory cytokines in the spinal cord. Behaviorally expressed DNP was determined by measuring the sensitivity of hindpaw skin to mechanical and thermal stimulation.

Results: There were 87.5% (77/88) rats which developed high blood glucose within 1-2 weeks following STZ injection. Of which, 70.13% ( = 54/77) animals exhibited DNP manifested as mechanical allodynia and/or thermal hyperalgesia. Intraperitoneal administration of vitamins B1/B6/B12 (100/100/2 mg/kg, one or multiple doses) significantly attenuated DNP without affecting the blood glucose. Expressions of P2X3 and TRPV1 in CGRP-positive and IB4-positive DRG neurons as well as the interleukin-1, tumor necrosis factor-, and nerve growth factor in the lumbar spinal cord were greatly increased in DNP rats. Such DNP-associated neurochemical alterations were also greatly suppressed by the B-vitamin treatment.

Conclusions: B-vitamin treatment can greatly suppress chronic DNP and DNP-associated increased activities of P2X3 and TRPV1 in DRG and the spinal proinflammatory cytokines, which may contribute to the pathogenesis of DNP. Systematic administration of B vitamins can be a strategy for DNP management in clinic.

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References

Vincent A, Feldman E . New insights into the mechanisms of diabetic neuropathy. Rev Endocr Metab Disord. 2004; 5(3):227-36. DOI: 10.1023/B:REMD.0000032411.11422.e0. View

Honda K, Koga K, Moriyama T, Koguchi M, Takano Y, Kamiya H . Intrathecal alpha2 adrenoceptor agonist clonidine inhibits mechanical transmission in mouse spinal cord via activation of muscarinic M1 receptors. Neurosci Lett. 2002; 322(3):161-4. DOI: 10.1016/s0304-3940(02)00073-3. View

Calcutt N, Backonja M . Pathogenesis of pain in peripheral diabetic neuropathy. Curr Diab Rep. 2008; 7(6):429-34. DOI: 10.1007/s11892-007-0072-9. View

Bernstein A . Vitamin B6 in clinical neurology. Ann N Y Acad Sci. 1990; 585:250-60. DOI: 10.1111/j.1749-6632.1990.tb28058.x. View

Otis J, Sanderson K, Hardway C, Pincus M, Tun C, Soumekh S . A randomized controlled pilot study of a cognitive-behavioral therapy approach for painful diabetic peripheral neuropathy. J Pain. 2013; 14(5):475-82. DOI: 10.1016/j.jpain.2012.12.013. View

Nadeau S, Filali M, Zhang J, Kerr B, Rivest S, Soulet D . Functional recovery after peripheral nerve injury is dependent on the pro-inflammatory cytokines IL-1β and TNF: implications for neuropathic pain. J Neurosci. 2011; 31(35):12533-42. PMC: 6703268. DOI: 10.1523/JNEUROSCI.2840-11.2011. View

Zhang Y, Huang Z, Liu S, Liu Y, Song A, Song X . WNT signaling underlies the pathogenesis of neuropathic pain in rodents. J Clin Invest. 2013; 123(5):2268-86. PMC: 3635721. DOI: 10.1172/JCI65364. View

Manni L, Florenzano F, Aloe L . Electroacupuncture counteracts the development of thermal hyperalgesia and the alteration of nerve growth factor and sensory neuromodulators induced by streptozotocin in adult rats. Diabetologia. 2011; 54(7):1900-8. DOI: 10.1007/s00125-011-2117-5. View

Song X, Hu S, Greenquist K, Zhang J, LaMotte R . Mechanical and thermal hyperalgesia and ectopic neuronal discharge after chronic compression of dorsal root ganglia. J Neurophysiol. 1999; 82(6):3347-58. DOI: 10.1152/jn.1999.82.6.3347. View

10.

Kaneda K, Kikuchi M, Kashii S, Honda Y, Maeda T, Kaneko S . Effects of B vitamins on glutamate-induced neurotoxicity in retinal cultures. Eur J Pharmacol. 1997; 322(2-3):259-64. DOI: 10.1016/s0014-2999(96)00997-1. View

11.

Uckay I, Jornayvaz F, Lebowitz D, Gastaldi G, Gariani K, Lipsky B . An Overview on Diabetic Foot Infections, including Issues Related to Associated Pain, Hyperglycemia and Limb Ischemia. Curr Pharm Des. 2018; 24(12):1243-1254. DOI: 10.2174/1381612824666180302145754. View

12.

Vinik A, Park T, Stansberry K, Pittenger G . Diabetic neuropathies. Diabetologia. 2000; 43(8):957-73. DOI: 10.1007/s001250051477. View

13.

Vinik A, Ullal J, Parson H, Casellini C . Diabetic neuropathies: clinical manifestations and current treatment options. Nat Clin Pract Endocrinol Metab. 2006; 2(5):269-81. DOI: 10.1038/ncpendmet0142. View

14.

Wilder-Smith E, Ong W, Guo Y, Chow A . Epidermal transient receptor potential vanilloid 1 in idiopathic small nerve fibre disease, diabetic neuropathy and healthy human subjects. Histopathology. 2007; 51(5):674-80. PMC: 2121152. DOI: 10.1111/j.1365-2559.2007.02851.x. View

15.

Hong S, Wiley J . Early painful diabetic neuropathy is associated with differential changes in the expression and function of vanilloid receptor 1. J Biol Chem. 2004; 280(1):618-27. DOI: 10.1074/jbc.M408500200. View

16.

Zhang X, Huang J, McNaughton P . NGF rapidly increases membrane expression of TRPV1 heat-gated ion channels. EMBO J. 2005; 24(24):4211-23. PMC: 1356334. DOI: 10.1038/sj.emboj.7600893. View

17.

Deng X, Wu M, Xu N, Ma P, Song X . Activation of ephrinB-EphB receptor signalling in rat spinal cord contributes to maintenance of diabetic neuropathic pain. Eur J Pain. 2016; 21(2):278-288. DOI: 10.1002/ejp.922. View

18.

Davies M, Brophy S, Williams R, Taylor A . The prevalence, severity, and impact of painful diabetic peripheral neuropathy in type 2 diabetes. Diabetes Care. 2006; 29(7):1518-22. DOI: 10.2337/dc05-2228. View

19.

Arnold R, Kwai N, Krishnan A . Mechanisms of axonal dysfunction in diabetic and uraemic neuropathies. Clin Neurophysiol. 2013; 124(11):2079-90. DOI: 10.1016/j.clinph.2013.04.012. View

20.

Tomic M, Vuckovic S, Stepanovic-Petrovic R, Micov A, Ugresic N, Prostran M . Analysis of the antinociceptive interactions in two-drug combinations of gabapentin, oxcarbazepine and amitriptyline in streptozotocin-induced diabetic mice. Eur J Pharmacol. 2009; 628(1-3):75-82. DOI: 10.1016/j.ejphar.2009.11.016. View