The Effects of Risedronate and Exercise on Osteoporotic Lumbar Rat Vertebrae and Their Sensory Innervation

• Published in: Spine (Philadelphia, Pa. 1976) Pa. 1976), 2010-10, Vol.35 (22), p.1974-1982
• Main Authors: ORITA, Sumihisa, OHTORI, Seiji, ISHIKAWA, Tetsuhiro, MIYAGI, Masayuki, OCHIAI, Nobuyasu, KISHIDA, Shunji, TAKASO, Masashi, AOKI, Yasuchika, TOYONE, Tomoaki, TAKAHASHI, Kazuhisa, KOSHI, Takana, YAMASHITA, Masaomi, YAMAUCHI, Kazuyo, INOUE, Gen, SUZUKI, Munetaka, EGUCHI, Yawara, KAMODA, Hiroto, ARAI, Gen
• Format: Article
• Language: English
• Subjects: Afferent Pathways - cytology; Afferent Pathways - drug effects; Afferent Pathways - physiology; Animals; Back Pain - etiology; Back Pain - physiopathology; Back Pain - therapy; Biological and medical sciences; Bone Density Conservation Agents - administration & dosage; Bone Density Conservation Agents - therapeutic use; Cells, Cultured; Cerebrospinal fluid. Meninges. Spinal cord; Disease Models, Animal; Etidronic Acid - administration & dosage; Etidronic Acid - analogs & derivatives; Etidronic Acid - therapeutic use; Female; Injuries of the nervous system and the skull. Diseases due to physical agents; Lumbar Vertebrae - drug effects; Lumbar Vertebrae - innervation; Medical sciences; Nervous system (semeiology, syndromes); Neurology; Nociceptors - cytology; Nociceptors - pathology; Osteoporosis - complications; Osteoporosis - physiopathology; Osteoporosis - therapy; Physical Conditioning, Animal - physiology; Rats; Rats, Sprague-Dawley; Risedronate Sodium; Sensory Receptor Cells - cytology; Sensory Receptor Cells - drug effects; Sensory Receptor Cells - pathology; Traumas. Diseases due to physical agents
• ISSN: 0362-2436; 1528-1159
• DOI: 10.1097/BRS.0b013e3181d5959e

Investigation of sensory innervation of rat osteoporotic lumbar vertebrae using in vitro and in vivo models. To investigate (1) sensory innervation of osteoporotic rat vertebrae, (2) effects of risedronate on sensory neurons, (3) effects of osteoporosis treatment on bone mineral densities (BMDs) and the sensory innervation. Osteoporotic patients without fractures sometimes experience vague low back pain of unknown origin. The mechanisms of osteoporosis treatments against the pain are unclear. (1) The expression of calcitonin gene-related peptide (CGRP) immunoreactive (-ir) or transient receptor potential vanilloid 1 (TRPV1)-ir nerve fibers in vertebrae and dorsal root ganglions (DRG) innervating L3 vertebrae of Sprague Dawley rats labeled with neurotracer were examined in control, sham, and ovariectomized (OVX) rats. (2) Cultured rat neonate DRG neurons in media containing different concentrations of risedronate were immunostained for CGRP, and we measured its activity using axonal length and proportion of CGRP-ir neurons. (3) BMDs and CGRP expression in DRG neurons innervating L3 vertebrae were examined in the following 5 groups: sham (treated with saline), OVX (saline), OVX+EXE (treadmill exercise), OVX+RIS (risedronate), and OVX+RIS+EXE (risedronate and exercise). (1) A few CGRP-ir or TRPV1-ir nerve fibers were observed in the bone marrow. CGRP or TRPV1 expression in DRG was elevated in the OVX group (P < 0.05). (2) The axonal length and proportion of CGRP-ir neurons were dose-dependently suppressed (P < 0.05). (3) BMDs improved and the CGRP expression decreased in the risedronate-treated groups (P < 0.05), especially in the OVX+RIS+EXE group. Sensory innervation of osteoporotic rat vertebrae showed increased expression of CGRP and TRPV1 in DRG neurons. Risedronate suppressed activity of CGRP-ir neurons in vitro, improved BMD, and decreased CGRP expression, especially together with exercise in vivo.