Neuroprotective and antihyperalgesic effects of orexin-A in rats with painful diabetic neuropathy
| Autor: | Zahra Hajializadeh, Ayat Kaeidi, Seddigheh Niknia, Mohammad Reza Mirzaei, Mohammad Reza Hajizadeh, Mehdi Mahmoodi, Alireza Khoshdel, Mohammad Ali Fahmidehkar |
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| Rok vydání: | 2018 |
| Předmět: |
Male
medicine.medical_specialty Diabetic neuropathy Central nervous system 030209 endocrinology & metabolism Neuroprotection Diabetes Mellitus Experimental 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Endocrinology Diabetic Neuropathies Internal medicine Diabetes mellitus Medicine Animals Rats Wistar bcl-2-Associated X Protein Analgesics Orexins Endocrine and Autonomic Systems business.industry General Medicine medicine.disease Streptozotocin Rats Nociception Peripheral neuropathy medicine.anatomical_structure Neuroprotective Agents Neurology Proto-Oncogene Proteins c-bcl-2 Spinal Cord Hyperalgesia Motor Skills medicine.symptom business 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Neuropeptides. 73 |
| ISSN: | 1532-2785 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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