Teneligliptin Exerts Antinociceptive Effects in Rat Model of Partial Sciatic Nerve Transection Induced Neuropathic Pain

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.

Carnosine Alleviates Knee Osteoarthritis and Promotes Synoviocyte Protection via Activating the Nrf2/HO-1 Signaling Pathway: An In-Vivo and In-Vitro Study

“…This suggests that CA was effective in reducing knee OA pain. The weight-bearing results are consistent with the previous study [ 50 , 65 ], which used natural compounds to reduce knee OA-induced pain.…”

GLP-1 Receptor Agonists in Neurodegeneration: Neurovascular Unit in the Spotlight

“…Furthermore, the peripheral-to-central propagation of aggregated alpha-synuclein in a transgenic mouse model leads to mechanical allodynia and impaired nociception [280]. Interestingly, enhancing GLP-1 by teneligliptin (DPP-4 inhibitor) in a rat model of partial sciatic nerve transaction ameliorated neuropathic pain and reduced inflammation in the spinal cord [284]. Similar experimental paradigms would be valuable to further elucidate the mechanism(s) that may underlie neuroprotection associated with GLP-1RAs, i.e., investigating whether GLP-1RAs directly affect protein aggregation via peripheral anti-inflammatory effects and/or prevent pathological processes in the CNS predominantly through the central effects.…”

New Advances on Pathophysiology of Diabetes Neuropathy and Pain Management: Potential Role of Melatonin and DPP-4 Inhibitors

“…Oral administration of DPP-4i such as teneligliptin (TEN) is known to possess analgesic effects in humans against thermal pain. In addition, TEN is also known to enhance glutathione antioxidant production within the cells ( Fan et al, 2015 ; Yoon, Kim, & Song, 2020 ; Kuthati, Rao, Busa, & Wong, 2021 ). Recently, several reports have concluded that activation of GLP-1R can suppress neuroinflammation and central sensitization, thereby attenuating neuropathic pain in animal models ( Xu et al, 2017 ; B.; Zhu et al, 2014 ).…”