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Article

Peripheral KATP activation inhibits pain sensitization induced by skin/muscle incision and retraction via the nuclear factor-κB/c-Jun N-terminal kinase signaling pathway

  • Authors:
    • Li‑Ping Qian
    • Shi‑Ren Shen
    • Jun‑Jie Chen
    • Lu‑Lu Ji
    • Su Cao
  • View Affiliations / Copyright

    Affiliations: Department of Anesthesiology, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China
  • Pages: 2632-2638
    |
    Published online on: July 27, 2016
       https://doi.org/10.3892/mmr.2016.5546
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Abstract

The aim of the current study was to assess the effect of pinacidil activation of ATP‑sensitive potassium (KATP) channels prior to skin/muscle incision and retraction (SMIR) surgery on peripheral and central sensitization, and investigate molecular interferential targets for preventive analgesia. Male Sprague-Dawley rats were randomly assigned to one of the following five groups: Control, incision (sham surgery), incision plus retraction (SMIR) group, SMIR plus pinacidil (pinacidil) group and the SMIR plus pyrrolidine dithiocarbamate (PDTC) group. The rats in the pinacidil and PDTC groups were intraperitoneally injected with pinacidil or PDTC, respectively, prior to the SMIR procedure. The mechanical withdrawal threshold (MWT) was determined. Western blotting was performed to detect the alterations in the subunits of the KATP channels, Kir6.1 and SUR2, levels of nuclear factor‑κB (NF‑κB) in the tissue around the incision and c‑Jun N‑terminal kinase (JNK) in the spinal cord. There was a significant increase observed in the levels of NF‑κB and JNK following SMIR surgery compared with the control group, and a significant reduction in MWT and the levels of Kir6.1 and SUR2. Additionally, intraperitoneal administration of pinacidil inhibited the reduction in MWT, and Kir6.1 and SUR2 levels. SMIR was observed to result in increases in the levels of NF‑κB and JNK. In addition, in the PDTC group, the alterations in MWT, NF‑κB, JNK, Kir6.1 and SUR2 resulting from SMIR were blocked. The results of the current study suggest that the deteriorations in the microenvironment resulting from the SMIR procedure can induce peripheral and central sensitization, and that the activation of peripheral KATP by pinacidil prior to SMIR is able to inhibit peripheral and central sensitization via the NF‑κB/JNK signaling pathway, thus resulting in preventive analgesia.
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1 

Fu ES, Zhang YP, Sagen J, Candiotti KA, Morton PD, Liebl DJ, Bethea JR and Brambilla R: Transgenic inhibition of glial NF-kappa B reduces pain behavior and inflammation after peripheral nerve injury. Pain. 148:509–518. 2010. View Article : Google Scholar :

2 

Manassero G, Repetto IE, Cobianchi S, Valsecchi V, Bonny C, Rossi F and Vercelli A: Role of JNK isoforms in the development of neuropathic pain following sciatic nerve transection in the mouse. Mol Pain. 8:392012. View Article : Google Scholar : PubMed/NCBI

3 

Julius D and Basbaum AI: Molecular mechanisms of nociception. Nature. 413:203–210. 2001. View Article : Google Scholar : PubMed/NCBI

4 

Linley JE, Rose K, Ooi L and Gamper N: Understanding inflammatory pain: Ion channels contributing to acute and chronic nociception. Pflugers Arch. 459:657–669. 2010. View Article : Google Scholar : PubMed/NCBI

5 

Inagaki N, Gonoi T, Clement JP, Wang CZ, Aguilar-Bryan L, Bryan J and Seino S: A family of sulfonylurea receptors determines the pharmacological properties of ATP-sensitive K+ channels. Neuron. 16:1011–1017. 1996. View Article : Google Scholar : PubMed/NCBI

6 

Coderre TJ and Bennett GJ: A hypothesis for the cause of complex regional pain syndrome-type I (reflex sympathetic dystrophy): Pain due to deep-tissue microvascular pathology. Pain Med. 11:1224–1238. 2010. View Article : Google Scholar : PubMed/NCBI

7 

Fan LH, Tian HY, Wang J, Huo JH, Hu Z, Ma AQ and Cao YX: Downregulation of Kir6.1/SUR2B channels in the obese rat aorta. Nutrition. 25:359–363. 2009. View Article : Google Scholar

8 

Roper J and Ashcroft FM: Metabolic inhibition and low internal ATP activate K-ATP channels in rat dopaminergic substantia nigra neurones. Pflügers Arch. 430:44–54. 1995. View Article : Google Scholar

9 

Yamada K and Inagaki N: Neuroprotection by KATP channels. J Mol Cell Cardiol. 38:945–949. 2005. View Article : Google Scholar : PubMed/NCBI

10 

Zoga V, Kawano T, Liang MY, Bienengraeber M, Weihrauch D, McCallum B, Gemes G, Hogan Q and Sarantopoulos C: KATP channel subunits in rat dorsal root ganglia: Alterations by painful axotomy. Mol Pain. 6:62010. View Article : Google Scholar : PubMed/NCBI

11 

Perimal EK, Akhtar MN, Mohamad AS, Khalid MH, Ming OH, Khalid S, Tatt LM, Kamaldin MN, Zakaria ZA, Israf DA, et al: Zerumbone-induced antinociception: Involvement of the L-arginine-nitric oxide-cGMP-PKC-K+ATP channel pathways. Basic Clin Pharmacol Toxicol. 108:155–162. 2011. View Article : Google Scholar

12 

Flatters SJ: Characterization of a model of persistent postoperative pain evoked by skin/muscle incision and retraction (SMIR). Pain. 135:119–130. 2008. View Article : Google Scholar

13 

Dixon WJ: Staircase bioassay: The up-and-down method. Neurosci Biobehav Rev. 15:47–50. 1991. View Article : Google Scholar : PubMed/NCBI

14 

Cao S, Qin Y, Chen J and Shen S: Effects of pinacidil on changes to the microenvironment around the incision site, of a skin/muscle incision and retraction, in a rat model of postoperative pain. Mol Med Rep. 12:829–836. 2015.PubMed/NCBI

15 

Brennan TJ, Zahn PK and Pogatazki-Zahn EM: Mechanisms of incisional pain. Anesthesiol Clin North America. 23:1–20. 2005. View Article : Google Scholar : PubMed/NCBI

16 

Reuben SS and Buvanendran A: Preventing the development of chronic pain after orthopaedic surgery with preventive multimodal analgesic techniques. J Bone Joint Surg Am. 89:1343–1358. 2007. View Article : Google Scholar : PubMed/NCBI

17 

Kawano T, Zoga V, McCallum JB, Wu HE, Gemes G, Liang MY, Abram S, Kwok WM, Hogan QH and Sarantopoulos CD: ATP-sensitive potassium currents in rat primary afferent neurons: Biophysical, pharmacological properties and alterations by painful nerve injury. Neuroscience. 162:431–443. 2009. View Article : Google Scholar : PubMed/NCBI

18 

Ploug KB, Amrutkar DV, Baun M, Ramachandran R, Iversen A, Lund TM, Gupta S, Hay-Schmidt A, Olesen J and Jansen-Olesen I: K(ATP) channel openers in the trigemino-vascular system. Cephalalgia. 32:55–65. 2012. View Article : Google Scholar

19 

Du X, Wang C and Zhang H: Activation of ATP-sensitive potassium channels antagonize nociceptive behavior and hyper-excitability of DRG neurons from rats. Mol Pain. 7:352011. View Article : Google Scholar

20 

Ko EA, Han J, Jung ID and Park WS: Physiological roles of K+ channels in vascular smooth muscle cells. J Smooth Muscle Res. 44:65–81. 2008. View Article : Google Scholar : PubMed/NCBI

21 

Flagg TP, Enkvetchakul D and Koster JC: Muscle KATP channels: Recent insights to energy sensing and myoprotection. Physiol Rev. 90:799–829. 2010. View Article : Google Scholar : PubMed/NCBI

22 

Matejíková J, Kucharská J, Pintérová M, Pancza D and Ravingerová T: Protection against ischemia-induced ventricular arrhythmias and myocardial dysfunction conferred by preconditioning in the rat heart: Involvement of mitochondrial K(ATP) channels and reactive oxygen species. Physiol Res. 58:9–19. 2009.

23 

Batchu SN, Chaudhary KR, El-Sikhry H, Yang W, Light PE, Oudit GY and Seubert JM: Role of PI3Kα and sarcolemmal ATP-sensitive potassium channels in epoxyeicosatrienoic acid mediated cardioprotection. J Mol Cardiol. 53:43–52. 2012. View Article : Google Scholar

24 

Nesic O, Sundberg LM, Herrera JJ, Mokkapati VU, Lee J and Narayana PA: Vascular endothelial growth factor and spinal cord injury pain. J Neurotrauma. 27:1793–1803. 2010. View Article : Google Scholar : PubMed/NCBI

25 

Freudenthal R, Boccia MM, Acosta GB, Blake MG, Merlo E, Baratti CM and Romano A: NF-kappaB transcription factor is required for inhibitory avoidance long-term memory in mice. Eur J Neurosci. 21:2845–2852. 2005. View Article : Google Scholar

26 

Guo Q, Robinson N and Mattson MP: Secreted beta-amyloid precursor protein counteracts the proapoptotic action of mutant presenilin-1 by activation of NF-kappaB and stabilization of calcium homeostasis. J Biol Chem. 273:12341–12351. 1998. View Article : Google Scholar : PubMed/NCBI

27 

Mattson MP and Meffert MK: Roles for NF-kappaB in nerve cell survival, plasticity and disease. Cell Death Differ. 13:852–860. 2006. View Article : Google Scholar : PubMed/NCBI

28 

Gilmore TD: Introduction to NF-kappaB: Players, pathways, perspectives. Oncogene. 25:6680–6684. 2006. View Article : Google Scholar : PubMed/NCBI

29 

Mattson MP: NF-kappaB in the survival and plasticity of neurons. Neurochem Res. 30:883–893. 2005. View Article : Google Scholar : PubMed/NCBI

30 

Shi W, Cui N, Wu Z, Yang Y, Zhang S, Gai H, Zhu D and Jiang C: Lipopolysaccharides up-regulate Kir6.1/SUR2B channel expression and enhance vascular KATP channel activity via NF-kappaB-dependent signaling. J Biol Chem. 285:3021–3029. 2010. View Article : Google Scholar

31 

Bonny C, Borsello T and Zine A: Targeting the JNK pathway as a therapeutic protective strategy for nervous system diseases. Rev Neurosci. 16:57–67. 2005.PubMed/NCBI

32 

Zhang Q, Wang J, Duan MT, Han SP, Zeng XY and Wang JY: NF-κB, ERK, p38 MAPK and JNK contribute to the initiation and/or maintenance of mechanical allodynia induced by tumor necrosis factor-alpha in the red nucleus. Brain Res Bull. 99:132–139. 2013. View Article : Google Scholar : PubMed/NCBI

33 

Gao YJ and Ji RR: Activation of JNK pathway in persistent pain. Neurosci Lett. 437:180–183. 2008. View Article : Google Scholar : PubMed/NCBI

34 

Benedetti G, Fredriksson L, Herpers B, Meerman J, van de Water B and de Graauw M: TNF-α-mediated NF-κB survival signaling impairment by cisplatin enhances JNK activation allowing synergistic apoptosis of renal proximal tubular cells. Biochem Pharmacol. 85:274–286. 2013. View Article : Google Scholar

35 

Li J, Yang L, Qin W, Zhang G, Yuan J and Wang F: Adaptive induction of growth differentiation factor 15 attenuates endothelial cell apoptosis in response to high glucose stimulus. PLoS One. 8:e655492013. View Article : Google Scholar : PubMed/NCBI

36 

Liu SF, Ye X and Malik AB: Inhibition of NF-kappaB activation by pyrrolidine dithiocarbamate prevents in vivo expression of proinflammatory genes. Circulation. 100:1330–1337. 1999. View Article : Google Scholar : PubMed/NCBI

37 

Zhao S, Zhang H, Cao D, Liu Y and Li X: Lipopolysaccharide exposure during pregnancy leads to aortic dysfunction in offspring rats. PloS One. 9:e1022732014. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Qian LP, Shen SR, Chen JJ, Ji LL and Cao S: Peripheral KATP activation inhibits pain sensitization induced by skin/muscle incision and retraction via the nuclear factor-κB/c-Jun N-terminal kinase signaling pathway. Mol Med Rep 14: 2632-2638, 2016.
APA
Qian, L., Shen, S., Chen, J., Ji, L., & Cao, S. (2016). Peripheral KATP activation inhibits pain sensitization induced by skin/muscle incision and retraction via the nuclear factor-κB/c-Jun N-terminal kinase signaling pathway. Molecular Medicine Reports, 14, 2632-2638. https://doi.org/10.3892/mmr.2016.5546
MLA
Qian, L., Shen, S., Chen, J., Ji, L., Cao, S."Peripheral KATP activation inhibits pain sensitization induced by skin/muscle incision and retraction via the nuclear factor-κB/c-Jun N-terminal kinase signaling pathway". Molecular Medicine Reports 14.3 (2016): 2632-2638.
Chicago
Qian, L., Shen, S., Chen, J., Ji, L., Cao, S."Peripheral KATP activation inhibits pain sensitization induced by skin/muscle incision and retraction via the nuclear factor-κB/c-Jun N-terminal kinase signaling pathway". Molecular Medicine Reports 14, no. 3 (2016): 2632-2638. https://doi.org/10.3892/mmr.2016.5546
Copy and paste a formatted citation
x
Spandidos Publications style
Qian LP, Shen SR, Chen JJ, Ji LL and Cao S: Peripheral KATP activation inhibits pain sensitization induced by skin/muscle incision and retraction via the nuclear factor-κB/c-Jun N-terminal kinase signaling pathway. Mol Med Rep 14: 2632-2638, 2016.
APA
Qian, L., Shen, S., Chen, J., Ji, L., & Cao, S. (2016). Peripheral KATP activation inhibits pain sensitization induced by skin/muscle incision and retraction via the nuclear factor-κB/c-Jun N-terminal kinase signaling pathway. Molecular Medicine Reports, 14, 2632-2638. https://doi.org/10.3892/mmr.2016.5546
MLA
Qian, L., Shen, S., Chen, J., Ji, L., Cao, S."Peripheral KATP activation inhibits pain sensitization induced by skin/muscle incision and retraction via the nuclear factor-κB/c-Jun N-terminal kinase signaling pathway". Molecular Medicine Reports 14.3 (2016): 2632-2638.
Chicago
Qian, L., Shen, S., Chen, J., Ji, L., Cao, S."Peripheral KATP activation inhibits pain sensitization induced by skin/muscle incision and retraction via the nuclear factor-κB/c-Jun N-terminal kinase signaling pathway". Molecular Medicine Reports 14, no. 3 (2016): 2632-2638. https://doi.org/10.3892/mmr.2016.5546
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