Yonsei Med J.  2014 Nov;55(6):1600-1605. 10.3349/ymj.2014.55.6.1600.

Increase of TRPV1-Immunoreactivity in Dorsal Root Ganglia Neurons Innervating the Femur in a Rat Model of Osteoporosis

Affiliations
  • 1Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan. sohtori@faculty.chiba-u.jp

Abstract

PURPOSE
Transient receptor potential vanilloid 1 (TRPV1) is a ligand-gated nonselective cation channel, which can be activated by capsaicin and other noxious stimuli. Recently, an association between bone pain and TRPV1 has been reported. However, the influence of osteoporosis on TRPV1 in the sensory system innervating the femur has not been reported.
MATERIALS AND METHODS
TRPV1-immunoreactive (ir) in dorsal root ganglia (DRG) neurons labeled with neurotracer [Fluoro-Gold (FG)] innervating the femurs of Sprague Dawley rats were examined in control, sham, and ovariectomized (OVX) rats. We evaluated osteoporosis in the femurs and compared the proportion of TRPV1-ir DRG neurons innervating femur between the 3 groups of rats.
RESULTS
OVX rats showed osteoporotic cancellous bone in the femur. FG labeled neurons were distributed from L1 to L6 DRG, but there was no significant difference in the proportion of labeled neurons between the 3 groups (p>0.05). The proportions of FG labeled TRPV1-ir DRG neurons were 1.7%, 1.7%, and 2.8% of DRG neurons innervating the femur, in control, sham-operated, and OVX rats, respectively. The proportion of TRPV1-ir neurons in DRG innervating the femur in OVX rats was significantly higher than that in control and sham-operated rats (p<0.05).
CONCLUSION
Under physiological conditions, DRG neurons innervating femurs in rats contain TRPV1. Osteoporosis increases the numbers of TRPV1-ir neurons in DRG innervating osteoporotic femurs in rats. These findings suggest that TRPV1 may have a role in sensory perception of osteoporotic femurs.

Keyword

Osteoporosis; pain; transient receptor potential vanilloid 1; femur

MeSH Terms

Animals
Female
Femur/*innervation/*metabolism
Ganglia, Spinal/*metabolism
Lumbar Vertebrae/*innervation/physiopathology
Neurons
Osteoporosis/complications
Rats
Rats, Sprague-Dawley
Stilbamidines
TRPV Cation Channels/*metabolism
Stilbamidines
TRPV Cation Channels

Figure

  • Fig. 1 HE staining of control and OVX femurs. OVX femur samples showed thinner cortex and more widely separated bone trabeculae with decreased density compared with samples from the control group. (A) Control. (B) OVX. HE, hematoxylin and eosin; OVX, ovariectomized.

  • Fig. 2 Innervation of the left femur. FG-labeled (A, B, and C) and TRPV1 immunoreactive (ir) DRG neurons (D, E, and F) [A and D (control), B and E (sham), and C and F (OVX) are same sections. Arrows indicate double labeled neurons]. FG, Fluoro-Gold; TRPV1, transient receptor potential vanilloid 1; DRG, dorsal root ganglia; OVX, ovariectomized.

  • Fig. 3 Distribution and proportion of FG-labeled DRG neurons innervating the left femur. FG-labeled DRG neurons were present in DRG from L1 through L6, and there was no significant difference in the proportion of FG-labeled neurons between the 3 groups. FG, Fluoro-Gold; DRG, dorsal root ganglia; OVX, ovariectomized.

  • Fig. 4 Distribution and proportion of FG-labeled and TRPV1-ir DRG neurons innervating the left femur. FG-labeled and TRPV1-ir DRG neurons innervating the left femur were present in DRG from L1 through L6. The proportion of FG-labeled and TRPV1-ir DRG neurons in OVX rats was significantly higher than those in control and sham-operated rats (*p<0.05). FG, Fluoro-Gold; TRPV1, transient receptor potential vanilloid 1; DRG, dorsal root ganglia; OVX, ovariectomized; ir, immunoreactive.


Reference

1. Ralston SH, Layfield R. Pathogenesis of Paget disease of bone. Calcif Tissue Int. 2012; 91:97–113.
Article
2. Mach DB, Rogers SD, Sabino MC, Luger NM, Schwei MJ, Pomonis JD, et al. Origins of skeletal pain: sensory and sympathetic innervation of the mouse femur. Neuroscience. 2002; 113:155–166.
Article
3. Mantyh WG, Jimenez-Andrade JM, Stake JI, Bloom AP, Kaczmarska MJ, Taylor RN, et al. Blockade of nerve sprouting and neuroma formation markedly attenuates the development of late stage cancer pain. Neuroscience. 2010; 171:588–598.
Article
4. Freeman KT, Koewler NJ, Jimenez-Andrade JM, Buus RJ, Herrera MB, Martin CD, et al. A fracture pain model in the rat: adaptation of a closed femur fracture model to study skeletal pain. Anesthesiology. 2008; 108:473–483.
5. Yang CJ, Wang XW, Li X, Wu GC, Wang YQ, Mao-Ying QL. A rat model of bone inflammation-induced pain by intra-tibial complete Freund's adjuvant injection. Neurosci Lett. 2011; 490:175–179.
Article
6. Jimenez-Andrade JM, Mantyh WG, Bloom AP, Freeman KT, Ghilardi JR, Kuskowski MA, et al. The effect of aging on the density of the sensory nerve fiber innervation of bone and acute skeletal pain. Neurobiol Aging. 2012; 33:921–932.
Article
7. Tominaga M, Caterina MJ, Malmberg AB, Rosen TA, Gilbert H, Skinner K, et al. The cloned capsaicin receptor integrates multiple pain-producing stimuli. Neuron. 1998; 21:531–543.
Article
8. Guo A, Vulchanova L, Wang J, Li X, Elde R. Immunocytochemical localization of the vanilloid receptor 1 (VR1): relationship to neuropeptides, the P2X3 purinoceptor and IB4 binding sites. Eur J Neurosci. 1999; 11:946–958.
Article
9. Yu L, Yang F, Luo H, Liu FY, Han JS, Xing GG, et al. The role of TRPV1 in different subtypes of dorsal root ganglion neurons in rat chronic inflammatory nociception induced by complete Freund's adjuvant. Mol Pain. 2008; 4:61.
Article
10. Niiyama Y, Kawamata T, Yamamoto J, Omote K, Namiki A. Bone cancer increases transient receptor potential vanilloid subfamily 1 expression within distinct subpopulations of dorsal root ganglion neurons. Neuroscience. 2007; 148:560–572.
Article
11. Niiyama Y, Kawamata T, Yamamoto J, Furuse S, Namiki A. SB366791, a TRPV1 antagonist, potentiates analgesic effects of systemic morphine in a murine model of bone cancer pain. Br J Anaesth. 2009; 102:251–258.
Article
12. Iwamoto J, Takeda T, Ichimura S, Matsu K, Uzawa M. Effects of cyclical etidronate with alfacalcidol on lumbar bone mineral density, bone resorption, and back pain in postmenopausal women with osteoporosis. J Orthop Sci. 2003; 8:532–537.
Article
13. Ohtori S, Akazawa T, Murata Y, Kinoshita T, Yamashita M, Nakagawa K, et al. Risedronate decreases bone resorption and improves low back pain in postmenopausal osteoporosis patients without vertebral fractures. J Clin Neurosci. 2010; 17:209–213.
Article
14. Brown MF, Hukkanen MV, McCarthy ID, Redfern DR, Batten JJ, Crock HV, et al. Sensory and sympathetic innervation of the vertebral endplate in patients with degenerative disc disease. J Bone Joint Surg Br. 1997; 79:147–153.
Article
15. Orita S, Ohtori S, Koshi T, Yamashita M, Yamauchi K, Inoue G, et al. The effects of risedronate and exercise on osteoporotic lumbar rat vertebrae and their sensory innervation. Spine (Phila Pa 1976). 2010; 35:1974–1982.
Article
16. Luo D, Zhang YW, Peng WJ, Peng J, Chen QQ, Li D, et al. Transient receptor potential vanilloid 1-mediated expression and secretion of endothelial cell-derived calcitonin gene-related peptide. Regul Pept. 2008; 150:66–72.
Article
17. Bonabello A, Galmozzi MR, Bruzzese T, Zara GP. Analgesic effect of bisphosphonates in mice. Pain. 2001; 91:269–275.
Article
18. Fulfaro F, Casuccio A, Ticozzi C, Ripamonti C. The role of bisphosphonates in the treatment of painful metastatic bone disease: a review of phase III trials. Pain. 1998; 78:157–169.
Article
19. Van Offel JF, Schuerwegh AJ, Bridts CH, Bracke PG, Stevens WJ, De Clerck LS. Influence of cyclic intravenous pamidronate on proinflammatory monocytic cytokine profiles and bone density in rheumatoid arthritis treated with low dose prednisolone and methotrexate. Clin Exp Rheumatol. 2001; 19:13–20.
20. Varenna M, Zucchi F, Ghiringhelli D, Binelli L, Bevilacqua M, Bettica P, et al. Intravenous clodronate in the treatment of reflex sympathetic dystrophy syndrome. A randomized, double blind, placebo controlled study. J Rheumatol. 2000; 27:1477–1483.
21. Constantin CE, Mair N, Sailer CA, Andratsch M, Xu ZZ, Blumer MJ, et al. Endogenous tumor necrosis factor alpha (TNFalpha) requires TNF receptor type 2 to generate heat hyperalgesia in a mouse cancer model. J Neurosci. 2008; 28:5072–5081.
Article
22. Kochukov MY, McNearney TA, Yin H, Zhang L, Ma F, Ponomareva L, et al. Tumor necrosis factor-alpha (TNF-alpha) enhances functional thermal and chemical responses of TRP cation channels in human synoviocytes. Mol Pain. 2009; 5:49.
23. Liu J, Liu X, Duan K, Zhang Y, Guo SW. The expression and functionality of transient receptor potential vanilloid 1 in ovarian endometriomas. Reprod Sci. 2012; 19:1110–1124.
Article
24. Suzuki M, Orita S, Miyagi M, Ishikawa T, Kamoda H, Eguchi Y, et al. Vertebral compression exacerbates osteoporotic pain in an ovariectomy-induced osteoporosis rat model. Spine (Phila Pa 1976). 2013; 38:2085–2091.
Article
Full Text Links
  • YMJ
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr