Beneficial effect of mirtazapine on diabetes-induced hyperalgesia: involvement of TRPV1 and ASIC1 channels in the spinal cord and dorsal root ganglion

ABSTRACT

Objectives: Neuropathic pain reduces the life qualities of patients with Diabetes mellitus. Clinical guidelines recommend relief in diabetic neuropathic pain through the use of some antidepressants, anticonvulsants, opioids as well as capsaicin cream or lidocaine patches. However, since the majority of patients do not or partially respond to current treatments, there is a growing necessity for new drugs increasing the pain relief in patients with diabetes. Therefore, based on the therapeutic potential of antidepressants on neuropathic pain, we investigated the promising antihyperalgesic effect of mirtazapine (MRT) in painful diabetic neuropathy.

Methods: Experimental diabetes was induced in rats by single intraperitoneal injection of 55 mg/kg dose of streptozocin (STZ). After 4 weeks of injection of STZ, MRT was administrated for 14 days at 40 mg/kg dose. Randall–Selitto and Hargreaves tests were applied for paw-withdrawal threshold and paw-withdrawal latency measurement. TRPV1 and ASIC1 expressions measured by Western blot in dorsal root ganglion and spinal cord.

Results: Administration of MRT significantly improved both of the decreased paw-withdrawal threshold and shortened the paw-withdrawal latency of diabetic rats, respectively. Besides, increased levels of TRPV1 and ASIC1 channels in dorsal root ganglion and spinal cord of diabetic rats, evaluated by Western blot method, were decreased following the MRT treatment.

Discussion: These data show, for the first time, that MRT has beneficial effects against diabetes-induced hyperalgesia, and that suppressive effect of this drug on TRPV1 and ASIC1 levels, which are increased in diabetic rats, may be some of the pharmacological mechanisms underlying the exhibited antihyperalgesic effect of MRT.

KEYWORDS:

• Acid sensing ion channel 1(ASIC1)
• hyperalgesia
• mirtazapine
• Transient receptor potential vanilloid 1(TRPV1)

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was funded by the Eskisehir Osmangazi University (ESOGU) Science Foundation Grant No. 2014-515.

Notes on contributors

Ezgi Bektur

Erhan Sahin: Erhan Sahin graduated from Hacettepe University, department of biology in Ankara, Turkey. Then he received his MSc degree from Gazi University in 2011 and PhD degree from Eskisehir Osmangazi University, department of Histology and Embryology in 2015. His research interests are in reproductive toxicology and sterile inflamation. He has been a research assistant at Eskisehir Osmangazi University Department of Histology and Embryology since 2011.

Erhan Şahin

Emre Ceyhan: Emre Ceyhan has a PhD degree. He graduated from Eskisehir Osmangazi University, department of biology and he has been a research assistant in the molecular biology department. His research interests are renal ischemia-reperfusion and liver regenaration.

Emre Ceyhan

Dilek Burukoglu Donmez: Dilek Burukoglu Donmez has a PhD degree and she graduated from Eskisehir Osmangazi University, department of biology. She has been an associate professor in Eskisehir Osmangazi University, department of Histology and Embryology. Her research interests are reproductive toxicology.

Dilek Burukoglu Donmez

Mediha Canbek: Mediha Canbek has a PhD degree. She has been a professor in the department of molecular biology in Eskisehir Osmangazi University. Her research interests are cell biology, molecular biology and regeneration.

Mediha Canbek

Cengiz Baycu: Cengiz Baycu has a PhD degree. After he retired from Eskisehir Osmangazi University, he started to work in Okan University and he has been a professor in the department of histology and embryology, Okan University. Her research interests are reproductive toxicology and hepatotoxicity.

Cengiz Baycu

Ozgur Devrim Can: Ozgur Devrim Can has a PhD degree. After she graduated from faculty of pharmacy, Anadolu University. She received her PhD degree in department of pharmacology in faculty of pharmacy, Anadolu University. She has been an associate professor in the same department. Her research interests are diabetic neuropathy.