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

Cao,Su; Qin,Yinbin; Chen,Junjie; Shen,Shiren

doi:10.3892/mmr.2015.3465

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

Authors:
- Su Cao
- Yinbin Qin
- Junjie Chen
- Shiren Shen
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Affiliations: Department of Anesthesiology, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China
Published online on: March 10, 2015 https://doi.org/10.3892/mmr.2015.3465
Pages: 829-836
Copyright: © Cao et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

The aim of the present study was to evaluate the influence of the microenvironment around an incision site, on peripheral and central sensitization. The effects of pinacidil activation of ATP‑sensitive potassium (KATP) channels prior to skin/muscle incision and retraction (SMIR) surgery were assessed. A total of 24 male Sprague Dawley rats were randomly assigned to four groups: Control, sham (incision operation), SMIR (incision plus retraction 1 h after the skin/muscle incision) and pinacidil (SMIR plus pinacidil). The rats in the pinacidil group were intraperitoneally injected with pinacidil prior to the SMIR procedure. The mechanical withdrawal threshold (MWT) was determined at each time point. The microvessel density (MVD) value was determined by immunohistochemistry, and western blotting was performed to analyze the relative protein expression levels of nerve growth factor (NGF), glucose transporter protein‑1 (GLUT1) and C‑jun N‑terminal kinases. There was a significant reduction in the levels of MVD, GLUT1 and MWT following SMIR surgery as compared with the incision alone, and a significant increase in the NGF protein expression levels. In the SMIR group, the MVD value was significantly increased seven days after surgery, as compared with three days after surgery. Additionally, intraperitoneal administration of pinacidil prior to the SMIR surgery inhibited the SMIR‑induced reduction in MWT and MVD and attenuated the SMIR‑induced GLUT1 reduction. The results of the present study suggest that the microenvironment around an incision site may affect the development of peripheral and central sensitization. In addition, pinacidil had an inhibitory effect on the formation of the inflammatory microenvironment around the incision site through activation of KATP channels, thereby inhibiting peripheral and central sensitization.

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1	Burke S and Shorten GD: When pain after surgery doesn’t go away…. Biochem Soc Trans. 37:318–322. 2009. View Article : Google Scholar : PubMed/NCBI
2	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
3	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
4	Sawayama H, Ishimoto T, Watanabe M, et al: High expression of glucose transporter 1 on primary lesions of esophageal squamous cell carcinoma is associated with hematogenous recurrence. Ann Surg Oncol. 21:1756–1762. 2014. View Article : Google Scholar
5	Bateman RM, Tokunaga C, Kareco T, Dorscheid DR and Walley KR: Myocardial hypoxia-inducible HIF-1alpha, VEGF, and GLUT1 gene expression is associated with microvascular and ICAM-1 heterogeneity during endotoxemia. Am J Physiol Heart Circ Physiol. 293:H448–H456. 2007. View Article : Google Scholar : PubMed/NCBI
6	Semaan A, Munkarah AR, Arabi H, et al: Expression of GLUT-1 in epithelial ovarian carcinoma: correlation with tumor cell proliferation, angiogenesis, survival and ability to predict optimal cytoreduction. Gynecol Oncol. 121:181–186. 2011. View Article : Google Scholar
7	Kolar P, Lach S, Gaber T, et al: Effects of celecoxib on the expression of osteoprotegerin, energy metabolism and cell viability in cultured human osteoblastic cells. Clin Exp Rheumatol. 27:99–107. 2009.PubMed/NCBI
8	Bie B, Wang Y, Cai YQ, et al: Upregulation of nerve growth factor in central amygdala increases sensitivity to opioid reward. Neuropsychopharmacology. 37:2780–2788. 2012. View Article : Google Scholar : PubMed/NCBI
9	Zhao J, Seereeram A, Nassar MA, et al: Nociceptor-derived brain-derived neurotrophic factor regulates acute and inflammatory but not neuropathic pain. Mol Cell Neurosci. 31:539–548. 2006. View Article : Google Scholar : PubMed/NCBI
10	Lewin GR, Winter J and McMahon SB: Regulation of afferent connectivity in the adult spinal cord by nerve growth factor. Eur J Neurosci. 4:700–707. 1992. View Article : Google Scholar : PubMed/NCBI
11	Priyanka HP, Bala P, Ankisettipalle S and ThyagaRajan S: Bacopa monnieri and L-deprenyl differentially enhance the activities of antioxidant enzymes and the expression of tyrosine hydroxylase and nerve growth factor via ERK 1/2 and NF-κB pathways in the spleen of female wistar rats. Neurochem Res. 38:141–152. 2013. View Article : Google Scholar
12	Fukui Y, Ohtori S, Yamashita M, et al: Low affinity NGF receptor (p75 neurotrophin receptor) inhibitory antibody reduces pain behavior and CGRP expression in DRG in the mouse sciatic nerve crush model. J Orthop Res. 28:279–283. 2010.
13	Gao YJ, Xu ZZ, Liu YC, Wen YR, Decosterd I and Ji RR: The c-Jun N-terminal kinase 1 (JNK1) in spinal astrocytes is required for the maintenance of bilateral mechanical allodynia under a persistent inflammatory pain condition. Pain. 148:309–319. 2010. View Article : Google Scholar :
14	Manassero G, Repetto IE, Cobianchi S, et al: 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
15	Zoga V, Kawano T, Liang MY, et al: KATP channel subunits in rat dorsal root ganglia: alterations by painful axotomy. Mol Pain. 6:62010. View Article : Google Scholar : PubMed/NCBI
16	Perimal EK, Akhtar MN, Mohamad AS, 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
17	Du X, Wang C and Zhang H: Activation of ATP-sensitive potassium channels antagonize nociceptive behavior and hyperexcitability of DRG neurons from rats. Mol Pain. 7:352011. View Article : Google Scholar : PubMed/NCBI
18	Xia H, Zhang D, Yang S, et al: Role of ATP-sensitive potassium channels in modulating nociception in rat model of bone cancer pain. Brain Res. 1554:29–35. 2014. View Article : Google Scholar : PubMed/NCBI
19	Romero TR, Guzzo LS, Perez AC, Klein A and Duarte ID: Noradrenaline activates the NO/cGMP/ATP-sensitive K(+) channels pathway to induce peripheral antinociception in rats. Nitric Oxide. 26:157–161. 2012. View Article : Google Scholar : PubMed/NCBI
20	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
21	Dixon WJ: Staircase bioassay: the up-and-down method. Neurosci Biobehav Rev. 15:47–50. 1991. View Article : Google Scholar : PubMed/NCBI
22	Weidner N, Semple JP, Welch WR and Folkman J: Tumor angio-genesis and metastasis - correlation in invasive breast carcinoma. N Engl J Med. 324:1–8. 1991. View Article : Google Scholar : PubMed/NCBI
23	Memis A, Ozden C, Ozdal OL, Guzel O, Han O and Seckin S: Effect of finasteride treatment on suburethral prostatic microvessel density in patients with hematuria related to benign prostate hyperplasia. Urol Int. 80:177–180. 2008. View Article : Google Scholar : PubMed/NCBI
24	Brennan TJ, Zahn PK and Pogatzki-Zahn EM: Mechanisms of incisional pain. Anesthesiol. Clin North America. 23:1–20. 2005.
25	Pogatzki-Zahn EM, Zahn PK and Brennan TJ: Postoperative pain - clinical implications of basic research. Best Pract Res Clin Anaesthesiol. 21:3–13. 2007. View Article : Google Scholar : PubMed/NCBI
26	de Mos M, Laferrière A, Millecamps M, et al: Role of NFkappaB in an animal model of complex regional pain syndrome-type I (CRPS-I). J Pain. 10:1161–1169. 2009. View Article : Google Scholar : PubMed/NCBI
27	Freund-Michel V and Frossard N: The nerve growth factor and its receptors in airway inflammatory diseases. Pharmacol Ther. 117:52–76. 2008. View Article : Google Scholar
28	Mousa SA, Cheppudira BP, Shaqura M, et al: Nerve growth factor governs the enhanced ability of opioids to suppress inflammatory pain. Brain. 130:502–513. 2007. View Article : Google Scholar
29	Ansari N, Khodagholi F, Amini M and Shaerzadeh F: Attenuation of LPS-induced apoptosis in NGF-differentiated PC12 cells via NF-κB pathway and regulation of cellular redox status by an oxazine derivative. Biochimie. 93:899–908. 2011. View Article : Google Scholar : PubMed/NCBI
30	Wang H, Long C, Duan Z, Shi C, Jia G and Zhang Y: A new ATP-sensitive potassium channel opener protects endothelial function in cultured aortic endothelial cells. Cardiovasc Res. 73:497–503. 2007. View Article : Google Scholar
31	Minamino T and Hori M: Protecting endothelial function: A novel therapeutic target of ATP-sensitive potassium channel openers. Cardiovasc Res. 73:448–449. 2007. View Article : Google Scholar
32	Shi W, Cui N, Wu Z, et al: 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 :
33	Fan LH, Tian HY, Wang J, et al: Downregulation of Kir6.1/SUR2B channels in the obese rat aorta. Nutrition. 25:359–363. 2009. View Article : Google Scholar