Increase of TRPV1-Immunoreactivity in Dorsal Root Ganglia Neurons Innervating the Femur in a Rat Model of Osteoporosis
0
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Purpose: Transient receptor potential vanilloid 1 (TRPV1) is a ligand-gated nonselectivecation 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 innervatingthe 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 femursand 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 osteoporoticfemurs.
Abstract
Purpose: Transient receptor potential vanilloid 1 (TRPV1) is a ligand-gated nonselectivecation 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 innervatingthe 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 femursand 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 osteoporoticfemurs.
참고문헌 (24)
- Ralston SH, "Pathogenesis of Paget disease of bone", Calcif Tissue Int, 91, pp.97~113 (2012)
- Mach DB, "Origins of skeletal pain: sensory and sympathetic innervation of the mouse femur", Neuroscience, 113, pp.155~166 (2002)
- Mantyh WG, "Blockade of nerve sprouting and neuroma formation markedly attenuates the development of late stage cancer pain", Neuroscience, 171, pp.588~598 (2010)
- Freeman KT, "A fracture pain model in the rat: adaptation of a closed femur fracture model to study skeletal pain", Anesthesiology, 108, pp.473~483 (2008)
- Yang CJ, "A rat model of bone inflammation-induced pain by intra-tibial complete Freund’s adjuvant injection", Neurosci Lett, 490, pp.175~179 (2011)
- Jimenez-Andrade JM, "The effect of aging on the density of the sensory nerve fiber innervation of bone and acute skeletal pain", Neurobiol Aging, 33, pp.921~932 (2012)
- Tominaga M, "The cloned capsaicin receptor integrates multiple pain-producing stimuli", Neuron, 21, pp.531~543 (1998)
- Guo A, "Immunocytochemical localization of the vanilloid receptor 1 (VR1): relationship to neuropeptides, the P2X3 purinoceptor and IB4 binding sites", Eur J Neurosci, 11, pp.946~958 (1999)
- Yu L, "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, 4, pp.61~ (2008)
- Niiyama Y, "Bone cancer increases transient receptor potential vanilloid subfamily 1 expression within distinct subpopulations of dorsal root ganglion neurons", Neuroscience, 148, pp.560~572 (2007)
- Niiyama Y, "SB366791, a TRPV1 antagonist, potentiates analgesic effects of systemic morphine in a murine model of bone cancer pain", Br J Anaesth, 102, pp.251~258 (2009)
- Iwamoto J, "Effects of cyclical etidronate with alfacalcidol on lumbar bone mineral density, bone resorption, and back pain in postmenopausal women with osteoporosis", J Orthop Sci, 8, pp.532~537 (2003)
- Ohtori S, "Risedronate decreases bone resorption and improves low back pain in postmenopausal osteoporosis patients without vertebral fractures", J Clin Neurosci, 17, pp.209~213 (2010)
- Brown MF, "Sensory and sympathetic innervation of the vertebral endplate in patients with degenerative disc disease", J Bone Joint Surg Br, 79, pp.147~153 (1997)
- Orita S, "The effects of risedronate and exercise on osteoporotic lumbar rat vertebrae and their sensory innervation", Spine (Phila Pa 1976), 35, pp.1974~1982 (2010)
- Luo D, "Transient receptor potential vanilloid 1-mediated expression and secretion of endothelial cell-derived calcitonin gene-related peptide", Regul Pept, 150, pp.66~72 (2008)
- Bonabello A, "Analgesic effect of bisphosphonates in mice", Pain, 91, pp.269~275 (2001)
- Fulfaro F, "The role of bisphosphonates in the treatment of painful metastatic bone disease: a review of phase III trials", Pain, 78, pp.157~169 (1998)
- Van Offel JF, "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, 19, pp.13~20 (2001)
- Varenna M, "Intravenous clodronate in the treatment of reflex sympathetic dystrophy syndrome. A randomized, double blind, placebo controlled study", J Rheumatol, 27, pp.1477~1483 (2000)
- Constantin CE, "Endogenous tumor necrosis factor alpha (TNFalpha) requires TNF receptor type 2 to generate heat hyperalgesia in a mouse cancer model", J Neurosci, 28, pp.5072~5081 (2008)
- Kochukov MY, "Tumor necrosis factor-alpha (TNF-alpha) enhances functional thermal and chemical responses of TRP cation channels in human synoviocytes", Mol Pain, 5, pp.49~ (2009)
- Liu J, "The expression and functionality of transient receptor potential vanilloid 1 in ovarian endometriomas", Reprod Sci, 19, pp.1110~1124 (2012)
- Suzuki M, "Vertebral compression exacerbates osteoporotic pain in an ovariectomy-induced osteoporosis rat model", Spine (Phila Pa 1976), 38, pp.2085~2091 (2013)