Teneligliptin Exerts Antinociceptive Effects in Rat Model of Partial Sciatic Nerve Transection Induced Neuropathic Pain
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 prol...
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MDPI AG
2021-09-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/10/9/1438 |
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| author | Yaswanth Kuthati Vaikar Navakanth Rao Prabhakar Busa Chih-Shung Wong |
| author_facet | Yaswanth Kuthati Vaikar Navakanth Rao Prabhakar Busa Chih-Shung Wong |
| author_sort | Yaswanth Kuthati |
| collection | DOAJ |
| description | 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 <i>Wistar</i> 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. |
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| last_indexed | 2024-03-10T07:57:42Z |
| publishDate | 2021-09-01 |
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| series | Antioxidants |
| spelling | doaj.art-fe09717a530f4a2f8ebd17348383307c2023-11-22T11:48:48ZengMDPI AGAntioxidants2076-39212021-09-01109143810.3390/antiox10091438Teneligliptin Exerts Antinociceptive Effects in Rat Model of Partial Sciatic Nerve Transection Induced Neuropathic PainYaswanth Kuthati0Vaikar Navakanth Rao1Prabhakar Busa2Chih-Shung Wong3Department of Anesthesiology, Cathy General Hospital, Taipei 280, TaiwanDepartment of Biomedical Sciences, Academia Sinica Institute, Taipei 11529, TaiwanDepartment of Anesthesiology, Cathy General Hospital, Taipei 280, TaiwanDepartment of Anesthesiology, Cathy General Hospital, Taipei 280, TaiwanNeuropathic 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 <i>Wistar</i> 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.https://www.mdpi.com/2076-3921/10/9/1438neuropathic painpartial sciatic nerve transectiondipeptidyl peptidase-4 inhibitorteneligliptinglucagon-like peptide 1glial fibrillary acidic protein |
| spellingShingle | Yaswanth Kuthati Vaikar Navakanth Rao Prabhakar Busa Chih-Shung Wong Teneligliptin Exerts Antinociceptive Effects in Rat Model of Partial Sciatic Nerve Transection Induced Neuropathic Pain Antioxidants neuropathic pain partial sciatic nerve transection dipeptidyl peptidase-4 inhibitor teneligliptin glucagon-like peptide 1 glial fibrillary acidic protein |
| title | Teneligliptin Exerts Antinociceptive Effects in Rat Model of Partial Sciatic Nerve Transection Induced Neuropathic Pain |
| title_full | Teneligliptin Exerts Antinociceptive Effects in Rat Model of Partial Sciatic Nerve Transection Induced Neuropathic Pain |
| title_fullStr | Teneligliptin Exerts Antinociceptive Effects in Rat Model of Partial Sciatic Nerve Transection Induced Neuropathic Pain |
| title_full_unstemmed | Teneligliptin Exerts Antinociceptive Effects in Rat Model of Partial Sciatic Nerve Transection Induced Neuropathic Pain |
| title_short | Teneligliptin Exerts Antinociceptive Effects in Rat Model of Partial Sciatic Nerve Transection Induced Neuropathic Pain |
| title_sort | teneligliptin exerts antinociceptive effects in rat model of partial sciatic nerve transection induced neuropathic pain |
| topic | neuropathic pain partial sciatic nerve transection dipeptidyl peptidase-4 inhibitor teneligliptin glucagon-like peptide 1 glial fibrillary acidic protein |
| url | https://www.mdpi.com/2076-3921/10/9/1438 |
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