鞘内注射ETAR拮抗药对大鼠骨癌疼痛改善情况及其对ERK通路的影响

Abstract
Figure/Table
References
Related Citation (15)

Download: PDF (939 KB) HTML (0 KB)
Export: BibTeX | EndNote (RIS)

Abstract Objective To observe the extent to which intrathecal injection of endothelin A receptor (ETAR) antagonist alleviates the pain of bone cancer pain (BCP) rats and the effect on extracellular regulatory protein kinase (ERK) pathway.Methods Sixty rats were selected for intrathecal catheterization and randomly divided into the sham operation group, sham operation + ETAR antagonist (sham+BQ123) group, bone cancer pain (BCP) group, and bone cancer pain + ETAR antagonist (BCP+BQ123) group. The BCP group and BCP+BQ123 group were inoculated with Walker256 cells in the bone marrow cavity of the distal femur to establish a BCP rat model. On the 14th day of modeling, 14 rats in the BCP+BQ123 group and sham + BQ123 group were injected with 7 μl of BQ123 intrathecally while 13 rats in the BCP group and 14 rats in the sham group were injected intrathecally with the same amount of normal saline. Immediately before intrathecal injection and 0.5, 1.0, 1.5, 2.0, 2.5, and 3.0 hours after injection, the pain behavior of rats in each group was evaluated in terms of the mechanical paw withdrawal threshold (PWT) and the number of spontaneous flinches (NSF). After the last assessment of pain behavior, the severity of bone destruction in each group was assessed via imaging. The expressions of endothelin 1 (ET1), ETAR, ERK1/2 and p-ERK1/2 were detected by RT-qPCR and Western blot.Results Compared with the sham group and sham + BQ123 group, PWT decreased while NSF increased before injection in the BCP group and BCP + BQ123 group (P<0.05). At T0.5-3.0 h after intrathecal injection, the PWT and NSF of the BCP group remained unchanged, while the PWT of the BCP + BQ123 group increased before it decreased, while the NSF decreased before it increased. Both the PWT and NSF reached the maximum and minimum at 1.5 hours, and returned to the pre-injection level at 3.0 hours. Tibia bone X-ray showed that tibia bone density was uniform in the sham group and sham + BQ123 group, and there was no loss of the bone cortex. BCP group suffered extensive bone destruction and severe bone cortical defects 14 days after injection. In the BCP + BQ123 group, there were small lesions of bone destruction in the distal femur, and some cortical defects. Compared with the sham group and sham + BQ123 group, the relative expressions of ET1, ETAR mRNA and protein and p-ERK1/2 protein in the spinal cord of the BCP group and BCP + BQ123 group were increased, but were lower in the BCP + BQ123 group than in the BCP group (P<0.05).Conclusions The pain response of BCP is related to spinal cord ET-1 and ETAR. Intrathecal injection of ETAR antagonist can effectively improve the pain response of BCP rats, possibly by inhibiting the ERK pathway of the spinal cord.

Key words： bone cancer pain endothelin A receptor pain extracellular regulatory protein kinase

Received: 15 October 2020

ZTFLH:

R738.1

	Service

	E-mail this article
	Add to my bookshelf
	Add to citation manager
	E-mail Alert
	RSS
	Articles by authors
	HE Yuanshan
	SU Hong
	YI Guoen
	ZHANG Min
	XU Peng
	LI Zeqing

Cite this article:

HE Yuanshan,SU Hong,YI Guoen等. Intrathecal injection of ETAR antagonist alleviates pain in rats with bone cancer pain and its effect on ERK pathway[J]. Med. J. Chin. Peop. Armed Poli. Forc., 2021, 32(4): 285-290.

URL:

http://journal08.magtechjournal.com/Jwk_wjyx/EN/ OR http://journal08.magtechjournal.com/Jwk_wjyx/EN/Y2021/V32/I4/285

[1]	Kirshner J J, McDonald M C 3rd, Kruter F, et al. NOLAN: a randomized, phase 2 study to estimate the effect of prophylactic naproxen or loratadine vs no prophylactic treatment on bone pain in patients with early-stage breast cancer receiving chemotherapy and pegfilgrastim[J]. Support Care Cancer, 2018, 26(4):1323-1334.
[2]	范金艳, 刘丽雅, 马洋. 康复外科护理对骨癌疼痛患者行微创手术的影响[J]. 中华肿瘤防治杂志, 2018, 25(2): 253-254.
[3]	刘红, 蒋远静, 刘水霞. 癌痛规范化治疗提高中重度癌痛患者生活质量的临床及护理分析[J]. 第三军医大学学报, 2018, 40(10): 934-938.
[4]	Tai L W, Pan Z, Sun L, et al. Suppression of Pax2 attenuates allodynia and hyperalgesia through ET-1-ETAR-NFAT5 signaling in a rat model of neuropathic pain[J]. Neuroscience, 2018, 384:139-151.
[5]	Portenoy R K, Ahmed E. Cancer pain syndromes[J]. Hematol Oncol Clin North Am, 2018, 32(3):371-386.
[6]	李晓青, 俞卫锋, 孙玉明, 等. Walker 256乳腺癌细胞构建大鼠胫骨骨癌痛模型[J]. 中国肿瘤生物治疗杂志, 2008, 15(1): 41-45.
[7]	Ibrahim M M, Patwardhan A, Gilbraith K B, et al. Long-lasting antinociceptive effects of green light in acute and chronic pain in rats[J]. Pain, 2017, 158(2): 347-360.
[8]	Harton L R, Richardson J R, Armendariz A, et al. Dissociation of morphine analgesic effects in the sensory and affective components of formalin-induced spontaneous pain in male and female rats[J]. Brain Res, 2017, 1658: 36-41.
[9]	钟丽红, 陈文宇, 林伟龙, 等. 中西医综合治疗骨癌疼痛的临床观察[J]. 中华中医药学刊, 2019, 37(2): 409-413.
[10]	Zhang H, Lund D M, Ciccone H A, et al. Peripherally restricted cannabinoid 1 receptor agonist as a novel analgesic in cancer-induced bone pain[J]. Pain, 2018, 159(9):1814-1823.
[11]	Gomes L O, Chichorro J G, Araya E I, et al. Facial hyperalgesia due to direct action of endothelin-1 in the trigeminal ganglion of mice[J]. J Pharm Pharmacol, 2018, 70(7): 893-900.
[12]	Pontes R B, Lisboa M R P, Pereira A F, et al. Involvement of endothelin receptors in peripheral sensory neuropathy induced by oxaliplatin in mice[J]. Neurotox Res, 2019, 36(4): 688-699.
[13]	Tang Y, Peng H, Liao Q, et al. Study of breakthrough cancer pain in an animal model induced by endothelin-1[J]. Neurosci Lett, 2016, 617:108-115.
[14]	Mantyh P W. Mechanisms that drive bone pain across the lifespan[J]. Br J Clin Pharmacol, 2019, 85(6):1103-1113.
[15]	Lee S H, Kwon S C, Ok S H, et al. Levobupivacaine-induced vasoconstriction involves caldesmon phosphorylation mediated by tyrosine kinase-induced ERK phosphorylation[J]. Eur J Pharmacol, 2019, 842:167-176.
[16]	Shenoy P A, Kuo A, Khan N, et al. The somatostatin receptor-4 agonist J-2156 alleviates mechanical hypersensitivity in a rat model of breast cancer induced bone pain[J]. Front Pharmacol, 2018, 9: 495.
[17]	Nakamura A, Ono H, Ando A, et al. Suppression of the acute upregulation of phosphorylated-extracellular regulated kinase in ventral tegmental area by a μ-opioid receptor agonist is related to resistance to rewarding effects in a mouse model of bone cancer[J]. J Pharmacol Sci, 2017, 133(1):9-17.