Abstract
AbstractClinical 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.
Funder
MEXT | Japan Society for the Promotion of Science
Publisher
Springer Science and Business Media LLC
Reference67 articles.
1. Scharla, S. et al. Skeletal pain in postmenopausal women with osteoporosis: prevalence and course during raloxifene treatment in a prospective observational study of 6 months duration. Current medical research and opinion 22, 2393–2402, https://doi.org/10.1185/030079906X154097 (2006).
2. Silverman, S. L., Piziak, V. K., Chen, P., Misurski, D. A. & Wagman, R. B. Relationship of health related quality of life to prevalent and new or worsening back pain in postmenopausal women with osteoporosis. The Journal of rheumatology 32, 2405–2409 (2005).
3. Orita, S., Ohtori, S., Inoue, G. & Takahashi, K. in Osteoporosis (ed Yannis, Dionyssiotis) Ch. 27, 541–554 (InTech) (2012).
4. Mantyh, P. W. The neurobiology of skeletal pain. The European journal of neuroscience 39, 508–519, https://doi.org/10.1111/ejn.12462 (2014).
5. Yoneda, T., Hiasa, M., Nagata, Y., Okui, T. & White, F. A. Acidic microenvironment and bone pain in cancer-colonized bone. BoneKEy reports 4, 690, https://doi.org/10.1038/bonekey.2015.58 (2015).
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