Teneligliptin Co-Infusion Alleviates Morphine Tolerance by Inhibition of Spinal Microglial Cell Activation in Streptozotocin-Induced Diabetic Rats

被引:5
作者
Kuthati, Yaswanth [1 ]
Rao, Vaikar Navakanth [2 ]
Huang, Wei-Hsiu [1 ]
Busa, Prabhakar [1 ]
Wong, Chih-Shung [1 ,3 ]
机构
[1] Cathy Gen Hosp, Dept Anesthesiol, Taipei 106, Taiwan
[2] Tzu Chi Univ, Sch Med, PhD Program Pharmacol & Toxicol, Hualien 970, Taiwan
[3] Inst Med Sci, Natl Def Med Ctr, Taipei 114, Taiwan
关键词
diabetic neuropathic pain; dipeptidyl peptidase-4 inhibitor; teneligliptin; microglia; morphine antinociceptive tolerance; DIPEPTIDYL PEPTIDASE-4 INHIBITOR; MU-OPIOID RECEPTORS; OXIDATIVE STRESS; NEUROPATHIC PAIN; COGNITIVE DEFICITS; MODEL; ANTINOCICEPTION; SITAGLIPTIN; ANTIOXIDANT; NEUROINFLAMMATION;
D O I
10.3390/antiox12071478
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Morphine (MOR) is a commonly prescribed drug for the treatment of moderate to severe diabetic neuropathic pain (DNP). However, long-term MOR treatment is limited by morphine analgesic tolerance (MAT). The activation of microglial cells and the release of glia-derived proinflammatory cytokines are known to play an important role in the development of MAT. In this study, we aimed to investigate the effects of the dipeptidyl peptidase-4 inhibitor (DPP-4i) teneligliptin (TEN) on MOR-induced microglial cell activation and MAT in DNP rats. DNP was induced in four groups of male Wistar rats through a single intraperitoneal injection of streptozotocin (STZ) (50 mg/kg, freshly dissolved in 5 mmol/L citrate buffer, pH 4.5). Sham rats were administered with the vehicle. Seven days after STZ injection, all rats were implanted with an intrathecal (i.t) catheter connected to a mini-osmotic pump, divided into five groups, and infused with the following combinations: sham + saline (1 & mu;L/h, i.t), DNP + saline (1 & mu;L/h, i.t), DNP + MOR (15 & mu;g/h, i.t), DNP + TEN (2 & mu;g/h, i.t), and DNP + MOR (15 & mu;g/h, i.t) + TEN (2 & mu;g/h, i.t) for 7 days at a rate of 1 & mu;L/h. The MAT was confirmed through the measurement of mechanical paw withdrawal threshold and tail-flick tests. The mRNA expression of neuroprotective proteins nuclear factor erythroid 2-related factor (Nrf2) and heme oxygenase-1 (HO-1) in the dorsal horn was evaluated by quantitative PCR (qPCR). Microglial cell activation and mononucleate cell infiltration in the spinal cord dorsal horn were assessed by immunofluorescence assay (IFA) and Western blotting (WB). The results showed that co-infusion of TEN with MOR significantly attenuated MAT in DNP rats through the restoration of neuroprotective proteins Nrf2 and HO-1 and suppression of microglial cell activation in the dorsal horn. Though TEN at a dose of 2 & mu;g has mild antinociceptive effects, it is highly effective in limiting MAT.
引用
收藏
页数:17
相关论文
共 75 条
  • [1] The hepatoprotective effect of sitagliptin against hepatic ischemia reperfusion-induced injury in rats involves Nrf-2/HO-1 pathway
    Abdel-Gaber, Seham A.
    Geddawy, Ayman
    Moussa, Rabab A.
    [J]. PHARMACOLOGICAL REPORTS, 2019, 71 (06) : 1044 - 1049
  • [2] Neuroprotective effects of vildagliptin in rat rotenone Parkinson's disease model: role of RAGE-NFκB and Nrf2 antioxidant signaling pathways
    Abdelsalam, Rania M.
    Safar, Marwa M.
    [J]. JOURNAL OF NEUROCHEMISTRY, 2015, 133 (05) : 700 - 707
  • [3] Repositioning of Omarigliptin as a once-weekly intranasal Anti-parkinsonian Agent
    Ayoub, Bassam M.
    Mowaka, Shereen
    Safar, Marwa M.
    Ashoush, Nermeen
    Arafa, Mona G.
    Michel, Haidy E.
    Tadros, Mariam M.
    Elmazar, Mohamed M.
    Mousa, Shaker A.
    [J]. SCIENTIFIC REPORTS, 2018, 8
  • [4] Opioids for Chronic Noncancer Pain A Systematic Review and Meta-analysis
    Busse, Jason W.
    Wang, Li
    Kamaleldin, Mostafa
    Craigie, Samantha
    Riva, John J.
    Montoya, Luis
    Mulla, Sohail M.
    Lopes, Luciane C.
    Vogel, Nicole
    Chen, Eric
    Kirmayr, Karin
    De Oliveira, Kyle
    Olivieri, Lori
    Kaushal, Alka
    Chaparro, Luis E.
    Oyberman, Inna
    Agarwal, Arnav
    Couban, Rachel
    Tsoi, Ludwig
    Lam, Tommy
    Vandvik, Per Olav
    Hsu, Sandy
    Bala, Malgorzata M.
    Schandelmaier, Stefan
    Scheidecker, Anne
    Ebrahim, Shanil
    Ashoorion, Vahid
    Rehman, Yasir
    Hong, Patrick J.
    Ross, Stephanie
    Johnston, Bradley C.
    Kunz, Regina
    Sun, Xin
    Buckley, Norman
    Sessler, Daniel I.
    Guyatt, Gordon H.
    [J]. JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2018, 320 (23): : 2448 - 2460
  • [5] Butul M., 2020, INT J BASIC CLIN PHA, V9, P729, DOI [10.18203/2319-2003.ijbcp20200729, DOI 10.18203/2319-2003.IJBCP20200729]
  • [6] Procyanidins alleviates morphine tolerance by inhibiting activation of NLRP3 inflammasome in microglia
    Cai, Yang
    Kong, Hong
    Pan, Yin-Bing
    Jiang, Lai
    Pan, Xiu-Xiu
    Hu, Liang
    Qian, Yan-Ning
    Jiang, Chun-Yi
    Liu, Wen-Tao
    [J]. JOURNAL OF NEUROINFLAMMATION, 2016, 13
  • [7] The Induction of Heme Oxygenase 1 Decreases Painful Diabetic Neuropathy and Enhances the Antinociceptive Effects of Morphine in Diabetic Mice
    Castany, Silvia
    Carcole, Mireia
    Leanez, Sergi
    Pol, Olga
    [J]. PLOS ONE, 2016, 11 (01):
  • [8] Antinociceptive effect of morphine, but not μ opioid receptor number, is attenuated in the spinal cord of diabetic rats
    Chen, SR
    Pan, HL
    [J]. ANESTHESIOLOGY, 2003, 99 (06) : 1409 - 1414
  • [9] Functional μ opioid receptors are reduced in the spinal cord dorsal horn of diabetic rats
    Chen, SR
    Sweigart, KL
    Lakoski, JM
    Pan, HL
    [J]. ANESTHESIOLOGY, 2002, 97 (06) : 1602 - 1608
  • [10] Dipeptidyl peptidase-4 inhibition improves endothelial senescence by activating AMPK/SIRT1/Nrf2 signaling pathway
    Chen, Zhihui
    Yu, Jing
    Fu, Menglu
    Dong, Ruolan
    Yang, Yan
    Luo, Jinlan
    Hu, Shuiqing
    Li, Wenhua
    Xu, Xizhen
    Tu, Ling
    [J]. BIOCHEMICAL PHARMACOLOGY, 2020, 177