Abstract
Neuropathic pain (NP), is a chronic pain resulting from nerve injury, with limited treatment options. Teneligliptin (TEN) is a dipeptidyl peptidase-4 inhibitor (DPP-4i) approved to treat type 2 diabetes. DPP-4is prevent the degradation of the incretin hormone glucagon-like peptide 1 (GLP-1) and prolong its circulation. Apart from glycemic control, GLP-1 is known to have antinociceptive and anti-inflammatory effects. Herein, we investigated the antinociceptive properties of TEN on acute pain, and partial sciatic nerve transection (PSNT)-induced NP in Wistar rats. Seven days post PSNT, allodynia and hyperalgesia were confirmed as NP, and intrathecal (i.t) catheters were implanted and connected to an osmotic pump for the vehicle (1 μL/h) or TEN (5 μg/1 μL/h) or TEN (5 μg) + GLP-1R antagonist Exendin-3 (9–39) amide (EXE) 0.1 μg/1 μL/h infusion. The tail-flick response, mechanical allodynia, and thermal hyperalgesia were measured for 7 more days. On day 14, the dorsal horn was harvested and used for Western blotting and immunofluorescence assays. The results showed that TEN had mild antinociceptive effects against acute pain but remarkable analgesic effects against NP. Furthermore, co-infusion of GLP-1R antagonist EXE with TEN partially reversed allodynia but not tail-flick latency. Immunofluorescence examination of the spinal cord revealed that TEN decreased the immunoreactivity of glial fibrillary acidic protein (GFAP). Taken together, our findings suggest that TEN is efficient in attenuation of PSNT-induced NP. Hence, the pleiotropic effects of TEN open a new avenue for NP management.
Highlights
Neuropathic pain (NP) results from the damage or injury to the nerves in the peripheral or central nervous system (CNS)
Rats were not subjected to nerve transection and the left sciatic nerve was gently exposed and muscle and skin are sutured Group II: Group II: partial sciatic nerve transection (PSNT)-vehicle group Group III: PSNT-TEN group
Immunofluorescence results showed that the numbers of glial fibrillary acidic protein (GFAP) positive cells in the spinal dorsal horn were significantly higher in the PSNT group than in the vehicle-treated animals
Summary
NP results from the damage or injury to the nerves in the peripheral or central nervous system (CNS). Available treatment options include the use of antidepressants, anticonvulsants, and anti-epileptics These medications are often combined with opioids to increase the analgesic efficacy in clinical practice [2,3,4,5,6]. TEN is reported to possess more ·OH scavenging ability compared to the naturally occurring antioxidant glutathione and to possess direct ·OH scavenging ability [17] These properties are not connected to DPP-4 inhibition as TEN has displayed free radical scavenging properties in DPP-4deficient animals [17]. Several previous studies have concluded that activation of GLP-1R can effectively suppress neuroinflammation and central sensitization, thereby alleviating neuropathic pain in various animal models [19,20,21,22,23,24,25]. In the present study, we examined the antinociceptive and neuroprotective effects of TEN in acute pain and PSNT-induced NP
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
