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Torbat Heydariyeh University of Medical Sciences

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

(2018) Neuroprotective and antihyperalgesic effects of orexin-A in rats with painful diabetic neuropathy. Neuropeptides.

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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. © 2018 Elsevier Ltd

Item Type: Article
Keywords: Apoptosis; Diabetic neuropathy; Nociception; Orexin-A; Rat
Journal or Publication Title: Neuropeptides
Journal Index: ISI, Pubmed, Scopus
Identification Number: 10.1016/j.npep.2018.11.001
Depositing User: دکتر محبوبه عبداللهی
URI: http://eprints.thums.ac.ir/id/eprint/816

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