Teriparatide relieves ovariectomy-induced hyperalgesia in rats, suggesting the involvement of functional regulation in primary sensory neurons by PTH-mediated signaling

• Published in: Scientific reports Vol. 10; no. 1; p. 5346
• Main Authors: Tanaka, Tomoya, Takao-Kawabata, Ryoko, Takakura, Aya, Shimazu, Yukari, Nakatsugawa, Momoko, Ito, Akitoshi, Lee, Ji-Won, Kawasaki, Koh, Iimura, Tadahiro
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 24-03-2020; Nature Publishing Group
• Subjects: 13; 13/51; 38; 38/39; 631/80/86/2363; 692/163/2743/316/801; Analgesics - pharmacology; Animals; Back pain; Bioinformatics; Bone Density - drug effects; Bone Density Conservation Agents - pharmacology; Calcium (intracellular); Cell size; Dorsal root ganglia; Female; Ganglia, Spinal - drug effects; Ganglia, Spinal - physiology; Gene Expression Profiling; Gene Expression Regulation - drug effects; Humanities and Social Sciences; Hyperalgesia; Hyperalgesia - drug therapy; Hyperalgesia - etiology; Inflammation; Microglia; Microglia - drug effects; multidisciplinary; Osteoporosis; Ovariectomy; Ovariectomy - adverse effects; Pain - drug therapy; Pain perception; Parathyroid; Parathyroid hormone; Parathyroid Hormone - metabolism; Rats, Sprague-Dawley; Receptor, Parathyroid Hormone, Type 1 - genetics; Ribonucleic acid; RNA; Rodents; Science; Science (multidisciplinary); Sensory neurons; Spinal Cord - cytology; Teriparatide - pharmacology; Withdrawal
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-020-62045-4

Clinical studies have reported that teriparatide (TPTD), a human parathyroid hormone analog, reduces back pain in osteoporotic patients. However, the mechanistic insights of this pharmacological action remain elusive. This study investigated the antinociceptive effect of TPTD mainly on primary sensory neurons in ovariectomized (OVX) rats. The plantar test showed thermal hyperalgesia in the OVX rats, which was significantly, but not fully, recovered immediately after the initial TPTD administration. The von Frey test also demonstrated reduced withdrawal threshold in the OVX rats. This was partially recovered by TPTD. Consistently, the number and size of spinal microglial cells were significantly increased in the OVX rats, while TPTD treatment significantly reduced the number but not size of these cells. RNA sequencing-based bioinformatics of the dorsal root ganglia (DRG) demonstrated that changes in neuro-protective and inflammatory genes were involved in the pharmacological effect of TPTD. Most neurons in the DRG expressed substantial levels of parathyroid hormone 1 receptor. TPTD treatment of the cultured DRG-derived neuronal cells reduced the cAMP level and augmented the intracellular calcium level as the concentration increased. These findings suggest that TPTD targets neuronal cells as well as bone cells to exert its pharmacological action.