Telmisartan inhibits hyperalgesia and inflammatory progression in a diabetic neuropathic pain model of Wistar rats

Worldwide, diabetic neuropathy (DN) is a major complication of diabetes mellitus. It affects around 15-25% in type-1, and 30-40% in type-2 diabetic patients, causing disabilities, and a high mortality rate. Neuropathic pain defined as a form of chronic pain resulting from damage or abnormal function of the central or peripheral nervous system.1 Patients with neuropathic pain frequently report sensory abnormalities such as burning sensations, hyperalgesia, allodynia, and dysesthesia.2 Diabetic neuropathy can also alter the patient’s quality of life by interfering with emotional well-being, which represents a challenge for clinicians because of its severity, chronicity, and resistance to some classical analgesics.3 The behavioral responses of diabetic rodents to thermal and mechanical hyper- and hypoalgesia as well as tactile allodynia to external stimuli have led to the identification of several mechanisms of abnormal sensation and pain in diabetes. It is confirmed that DN is characterized by neuronal degeneration and marked alterations in neural growth factors such as nerve growth factor (NGF) and insulin-like growth factor (IGF).4 Despite the availability of therapies to alleviate the symptoms of DN, a limited number of medications are available to control its basic causes. Diabetic associated disability and premature mortality are also caused by vascular complications, and several observational reports suggest the potential benefits of intensive blood pressure lowering of diabetic patients.5 The use of angiotensin converting enzyme inhibitors (ACEI) or an angiotensin receptor blocker (ARB) is recommended by current hypertension guidelines for patients with diabetes to achieve a target blood pressure level of 130/80 mm Hg or lower.5 The correlation between the renin angiotensin system and diabetic complications has been observed. Besides being clinically effective in diabetic nephropathy, ACEI or ARBs can improve nerve conduction deficit during peripheral DN in both animal models and human clinical studies. Furthermore, it has been suggested that ARBs are beneficial for nerve regeneration deficits in peripheral DN.6,7 Peroxisome proliferator-activated receptor-γ (PPAR-γ) is a nuclear receptor that activates cellular metabolism leading to cellular growth and differentiation,8 and improved insulin sensitivity.9 The beneficial effects of PPAR-γ ligands were demonstrated in experimental DN by suppressing the angiotensin type receptor 1 (AT1R) expression.10 The PPAR-γ ligands also have anti-inflammatory and antioxidant properties, which are known to be beneficial for microvascular complications in diabetes.9 Telmisartan (TMT) (Micardis®) is one of the most widely used antihypertensives for diabetic patients. It is an ARB with a nephro-protective11 and neuro-protective effect against retinal inflammation.12 Recently, we reported that TMT increases the levels of neurotrophic factors, endogenous antioxidants, and reduces the signs of apoptosis efficiently in diabetic retina.13 The present study was designed to investigate the potential neuro-protective effects of TMT (Micardis®) in a Wistar rat model of peripheral DN of streptozotocin-induced diabetes.