Repository of Research and Investigative Information

Repository of Research and Investigative Information

Rafsanjan University of Medical Sciences

Neuroprotective and antihyperalgesic effects of orexin-A in rats with painful diabetic neuropathy

(2019) Neuroprotective and antihyperalgesic effects of orexin-A in rats with painful diabetic neuropathy. Neuropeptides. pp. 34-40.

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Abstract

Aim of study: Diabetes mellitus is related to the development of neuronal tissue injury in different peripheral and central nervous system regions. A common complication of diabetes is painful diabetic peripheral neuropathy (PDN). We have studied the neuroprotective and anti-nociceptive properties of neuropeptide orexin-A in an animal experimental model of diabetic neuropathy. Methods: All experiments were carried out on male Wistar rats (220-250 g). Diabetes was induced by a single intraperitoneal injection of 55 mg/kg (i.p.) streptozotocin (STZ). Orexin-A was chronically administrated into the implanted intrathecal catheter (0.6, 2.5 and 5 nM/L, daily, 4 weeks). The tail-flick and rotarod treadmill tests were used to evaluate the nociceptive threshold and motor coordination of these diabetic rats, respectively. Cleaved caspase-3, Bax, Bcl2 and the Bax/Bcl-2 ratio, as the biochemical indicators of apoptosis, were investigated in the dorsal half of the lumbar spinal cord tissue by western blotting method. Results: Treatment of the diabetic rats with orexin-A (5 nM/L) significantly attenuated the hyperalgesia and motor deficit in diabetic animals. Furthermore, orexin-A (5 nM/L) administration suppressed pro-apoptotic cleaved caspase-3 and Bax proteins. Also, orexin-A (5 nM/L) reduced the expression of Bax/Bcl-2 ratio in spinal cord dorsal half of rats with PDN. Conclusions: Altogether our data suggest that the orexin-A has anti-hyperalgesic and neuroprotective effects in rats with PDN. Cellular mechanisms underlying the observed effects may, at least partially, be related to reducing the neuronal apoptosis.

Item Type: Article
Keywords: Diabetic neuropathy Orexin-A Apoptosis Nociception Rat type-1 receptor antagonism glucose-induced apoptosis in-vitro hypocretin orexin messenger-rna withdrawal model motor modulation prevents
Subjects: QU Biochemistry. Cell Biology and Genetics > QU 100-133 Biochemistry of the Human Body
Divisions: Education Vice-Chancellor Department > Faculty of Medicine > Department of Basic Science > Department of Clinical Biochemistry
Page Range: pp. 34-40
Journal or Publication Title: Neuropeptides
Journal Index: ISI, Pubmed, Scopus
Volume: 73
Publisher: CHURCHILL LIVINGSTONE, JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND
Identification Number: https://doi.org/10.1016/j.npep.2018.11.001
Depositing User: خانم مهتاب اکبری
URI: http://eprints.rums.ac.ir/id/eprint/6616

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