Elevated expression of transient receptor potential vanilloid type 1 in dorsal root ganglia of rats with endometriosis

Lian,Yu‑Ling; Cheng,Ming‑Jun; Zhang,Xian‑Xia; Wang,Li

doi:10.3892/mmr.2017.6783

Elevated expression of transient receptor potential vanilloid type 1 in dorsal root ganglia of rats with endometriosis

Authors:
- Yu‑Ling Lian
- Ming‑Jun Cheng
- Xian‑Xia Zhang
- Li Wang
View Affiliations

Affiliations: Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200011, P.R. China
Published online on: June 15, 2017 https://doi.org/10.3892/mmr.2017.6783
Pages: 1920-1926
Copyright: © Lian et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Pain is the most pronounced complaint of women with endometriosis, however the underlying mechanism is still poorly understood. In the present study, the authors evaluate the effect of transient receptor potential vanilloid type 1 (TRPV1) of dorsal root ganglia (DRG) on endometriosis-associated pain. A total of 36 SD rats were randomly divided into a sham group (n=9) and a Model group (n=27), accepted auto‑transplanted pieces of fat or uterus to the pelvic cavity. At 4 weeks, the Model group was randomly subdivided into the following groups: ENDO group (no treatment, n=9), BCTC group (Model + BCTC, an antagonist of TRPV1, n=9), Vehicle group (Model + cyclodextrin, the vehicle of BCTC, n=9). Tail‑flick test was performed prior to surgery, 1 h prior to and following treatment of BCTC or cyclodextrin. The expression of TRPV1, substance P (SP), calcitonin gene‑related peptide (CGRP) in L1‑L6 DRG was measured via immunohistochemistry, western blotting and RT‑qPCR. The results indicated that the Model group exhibited a signiﬁcant decrease in tail flick latency compared to pre‑surgical baseline, and the expression of TRPV1, SP, CGRP protein and mRNA in L1‑L6 DRG signiﬁcantly increased compared to the sham group. BCTC significantly improved tail flick latency, and downregulated the expression of TRPV1, SP and CGRP protein and mRNA levels in L1‑L6 DRG compared to ENDO group. However, there were no significant differences of those in Vehicle group compared with the ENDO group. Taken together, the current study provides evidence that TRPV1 expressed in DRG may serve an important role in endometriosis-associated pain.

View Figures

View References

1	Eskenazi B and Warner ML: Epidemiology of endometriosis. Obstet Gyn Clin North Am. 24:235–258. 1997. View Article : Google Scholar
2	Asante A and Taylor RN: Endometriosis: the role of neuroangiogenesis. In: Annual Review of PhysiologyJulius D and Clapham DE: Annual Reviews. 73. Palo Alto: pp. 163–182. 2011
3	Baron R: Mechanisms of disease: Neuropathic pain-a clinical perspective. Nat Clinl Pract Neuro. 2:95–106. 2006. View Article : Google Scholar
4	Anaf V, El Nakadi I, de Moor V, Chapron C, Pistofidis G and Noel JC: Increased nerve density in deep infiltrating endometriotic nodules. Gynecol Obstet Inves. 71:112–117. 2011. View Article : Google Scholar
5	Tokushige N, Markham R, Russell P and Fraser IS: Nerve fibres in peritoneal endometriosis. Hum Reprod. 21:3001–3007. 2006. View Article : Google Scholar : PubMed/NCBI
6	Anaf V, Simon P, El Nakadi I, Fayt I, Simonart T, Buxant F and Noel JC: Hyperalgesia, nerve infiltration and nerve growth factor expression in deep adenomyotic nodules, peritoneal and ovarian endometriosis. Hum Reprod. 17:1895–1900. 2002. View Article : Google Scholar : PubMed/NCBI
7	Berkley KJ, Rapkin AJ and Papka RE: The pains of endometriosis. Science. 308:1587–1589. 2005. View Article : Google Scholar : PubMed/NCBI
8	Rose KE, Lunardi N, Boscolo A, Dong X, Erisir A, Jevtovic-Todorovic V and Todorovic SM: Immunohistological demonstration of CaV3.2 T-type voltage-gated calcium channel expression in soma of dorsal root ganglion neurons and peripheral axons of rat and mouse. Neuroscience. 250:263–274. 2013. View Article : Google Scholar : PubMed/NCBI
9	Wang Y: The functional regulation of TRPV1 and its role in pain sensitization. Neurochem Res. 33:2008–2012. 2008. View Article : Google Scholar : PubMed/NCBI
10	Chen HS, He X, Wang Y, Wen WW, You HJ and Arendt-Nielsen L: Roles of capsaicin-sensitive primary afferents in differential rat models of inflammatory pain: A systematic comparative study in conscious rats. Exp Neurol. 204:244–251. 2007. View Article : Google Scholar : PubMed/NCBI
11	Hagenacker T and Büsselberg D: Modulation of intracellular calcium influences capsaicin-induced currents of TRPV-1 and voltage-activated channel currents in nociceptive neurones. J Peripher Nerv Syst. 12:277–284. 2007. View Article : Google Scholar : PubMed/NCBI
12	Caterina MJ, Schumacher MA, Tominaga M, Rosen TA, Levine JD and Julius D: The capsaicin receptor: A heat-activated ion channel in the pain pathway. Nature. 389:816–824. 1997. View Article : Google Scholar : PubMed/NCBI
13	Caterina MJ and Julius D: The vanilloid receptor: A molecular gateway to the pain pathway. Annu Rev Neurosci. 24:487–517. 2001. View Article : Google Scholar : PubMed/NCBI
14	Nie JC, Liu XS and Guo SW: Immunoreactivity of oxytocin receptor and transient receptor potential vanilloid type 1 and its correlation with dysmenorrhea in adenomyosis. Am J Obstet Gynecol. 202:346.e1–e8. 2010. View Article : Google Scholar
15	Tékus V, Bölcskei K, Kis-Varga A, Dézsi L, Szentirmay E, Visegrády A, Horváth C, Szolcsányi J and Petho G: Effect of transient receptor potential vanilloid 1 (TRPV1) receptor antagonist compounds SB705498, BCTC and AMG9810 in rat models of thermal hyperalgesia measured with an increasing-temperature water bath. Eur J Pharmacol. 641:135–141. 2010. View Article : Google Scholar : PubMed/NCBI
16	Tanaka H, Shimaya A, Kiso T, Kuramochi T, Shimokawa T and Shibasaki M: Enhanced insulin secretion and sensitization in diabetic mice on chronic treatment with a transient receptor potential vanilloid 1 antagonist. Life Sci. 88:559–563. 2011. View Article : Google Scholar : PubMed/NCBI
17	de Winter BY, Bredenoord AJ, van Nassauw L, de Man JG, de Schepper HU, Timmermans JP and Pelckmans PA: Involvement of afferent neurons in the pathogenesis of endotoxin-induced ileus in mice: Role of CGRP and TRPV1 receptors. Eur J Pharmacol. 615:177–184. 2009. View Article : Google Scholar : PubMed/NCBI
18	Chaban VV: Visceral sensory neurons that innervate both uterus and colon express nociceptive TRPv1 and P2×3 receptors in rats. Ethn Dis. 18 2 Suppl 2:S2-20-42008.PubMed/NCBI
19	Liu M, Liu X, Zhang Y and Guo SW: Valproic acid and progestin inhibit lesion growth and reduce hyperalgesia in experimentally induced endometriosis in rats. Reprod Sci. 19:360–373. 2012. View Article : Google Scholar : PubMed/NCBI
20	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
21	Hara T, Chiba T, Abe K, Makabe A, Ikeno S, Kawakami K, Utsunomiya I, Hama T and Taguchi K: Effect of paclitaxel on transient receptor potential vanilloid 1 in rat dorsal root ganglion. Pain. 154:882–889. 2013. View Article : Google Scholar : PubMed/NCBI
22	Jänig W and Koltzenburg M: On the function of spinal primary afferent-fibers supplying colon and urinary-bladder. J Auton Nerv Syst. 30 Suppl:S89–S96. 1990. View Article : Google Scholar : PubMed/NCBI
23	McMahon SB: Sensitisation of gastrointestinal tract afferents. Gut. 53 Suppl 2:ii13–ii15. 2004. View Article : Google Scholar : PubMed/NCBI
24	Xu X, Wang P, Zou X, Li D, Fang L and Lin Q: Increases in transient receptor potential vanilloid-1 mRNA and protein in primary afferent neurons stimulated by protein kinase C and their possible role in neurogenic inflammation. J Neurosci Res. 87:482–494. 2009. View Article : Google Scholar : PubMed/NCBI
25	Amaya F, Oh-Hashi K, Naruse Y, Iijima N, Ueda M, Shimosato G, Tominaga M, Tanaka Y and Tanaka M: Local inflammation increases vanilloid receptor 1 expression within distinct subgroups of DRG neurons. Brain Res. 963:190–196. 2003. View Article : Google Scholar : PubMed/NCBI
26	Tominaga M, Caterina MJ, Malmberg AB, Rosen TA, Gilbert H, Skinner K, Raumann BE, Basbaum AI and Julius D: The cloned capsaicin receptor integrates multiple pain-producing stimuli. Neuron. 21:531–543. 1998. View Article : Google Scholar : PubMed/NCBI
27	Valenzano KJ, Grant ER, Wu G, Hachicha M, Schmid L, Tafesse L, Sun Q, Rotshteyn Y, Francis J, Limberis J, et al: N-(4-tertiarybutylphenyl)-4-(3-chloropyridin-2-yl)tetrahydropyrazine-1(2H)-carbox-amide (BCTC), a novel, orally effective vanilloid receptor 1 antagonist with analgesic properties: I. In vitro characterization and pharmacokinetic properties. J Pharmacol Exp Ther. 306:377–386. 2003. View Article : Google Scholar : PubMed/NCBI
28	Khasar SG, Lin YH, Martin A, Dadgar J, McMahon T, Wang D, Hundle B, Aley KO, Isenberg W, McCarter G, et al: A novel nociceptor signaling pathway revealed in protein kinase C epsilon mutant mice. Neuron. 24:253–260. 1999. View Article : Google Scholar : PubMed/NCBI
29	Jung J, Shin JS, Lee SY, Hwang SW, Koo J, Cho H and Oh U: Phosphorylation of vanilloid receptor 1 by Ca²⁺/calmodulin-dependent kinase II regulates its vanilloid binding. J Biol Chem. 279:7048–7054. 2004. View Article : Google Scholar : PubMed/NCBI
30	Aley KO, Martin A, McMahon T, Mok J, Levine JD and Messing RO: Nociceptor sensitization by extracellular signal-regulated kinases. J Neurosci. 21:6933–6939. 2001.PubMed/NCBI
31	Kilo S, Harding-Rose C, Hargreaves KM and Flores CM: Peripheral CGRP release as a marker for neurogenic inflammation: A model system for the study of neuropeptide secretion in rat paw skin. Pain. 73:201–207. 1997. View Article : Google Scholar : PubMed/NCBI
32	Kessler F, Habelt C, Averbeck B, Reeh PW and Kress M: Heat-induced release of CGRP from isolated rat skin and effects of bradykinin and the protein kinase C activator PMA. Pain. 83:289–295. 1999. View Article : Google Scholar : PubMed/NCBI
33	Qiao LY and Grider JR: Up-regulation of calcitonin gene-related peptide and receptor tyrosine kinase TrkB in rat bladder afferent neurons following TNBS colitis. Exp Neurol. 204:667–679. 2007. View Article : Google Scholar : PubMed/NCBI
34	Linhart O, Obreja O and Kress M: The inflammatory mediators serotonin, prostaglandin E2 and bradykinin evoke calcium influx in rat sensory neurons. Neuroscience. 118:69–74. 2003. View Article : Google Scholar : PubMed/NCBI
35	Zhang N, Inan S, Cowan A, Sun R, Wang JM, Rogers TJ, Caterina M and Oppenheim JJ: A proinflammatory chemokine, CCL3, sensitizes the heat- and capsaicin-gated ion channel TRPV1. Proc Natl Acad Sci USA. 102:4536–4541. 2005. View Article : Google Scholar : PubMed/NCBI
36	Olah Z, Karai L and Iadarola MJ: Protein kinase C(alpha) is required for vanilloid receptor 1 activation. Evidence for multiple signaling pathways. J Biol Chem. 277:35752–35759. 2002. View Article : Google Scholar : PubMed/NCBI
37	Zhang Y, Malmberg AB, Yaksh TL, Sjölund B, Sundler F and Håkanson R: Capsaicin-evoked release of pituitary adenylate cyclase activating peptide (PACAP) and calcitonin gene-related peptide (CGRP) from rat spinal cord in vivo. Regul Pept. 69:83–87. 1997. View Article : Google Scholar : PubMed/NCBI
38	Szallasi A and Blumberg PM: Vanilloid (capsaicin) receptors and mechanisms. Pharmacol Rev. 51:159–212. 1999.PubMed/NCBI
39	Lin Q, Li D, Xu X, Zou X and Fang L: Roles of TRPV1 and neuropeptidergic receptors in dorsal root reflex-mediated neurogenic inflammation induced by intradermal injection of capsaicin. Mol Pain. 3:302007. View Article : Google Scholar : PubMed/NCBI
40	Stratton P and Berkley KJ: Chronic pelvic pain and endometriosis: Translational evidence of the relationship and implications. Hum Reprod Update. 17:327–346. 2011. View Article : Google Scholar : PubMed/NCBI