Abstract
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.
Highlights
Clinical studies have reported that teriparatide (TPTD), a human parathyroid hormone analog, reduces back pain in osteoporotic patients
This study investigated the antinociceptive effect of TPTD in OVX rats
We applied 2 pain-related behavioral tests—the plantar test and the von Frey test—to OVX rats to experimentally evaluate whether or not TPTD exerts an antinociceptive effect on this osteoporotic animal model, as has been observed in several clinical reports[15,16,17,18,19,20,21,22,23,24,25]
Summary
Clinical studies have reported that teriparatide (TPTD), a human parathyroid hormone analog, reduces back pain in osteoporotic patients. A possible causative mechanism of osteoporotic pain is chronic neuronal excitement in intraosseous sensory nerve systems by acids and inflammatory cytokines produced by the activation of osteoclasts, as well as monocytes and macrophages, due to estrogen deficiency[3,4]. This mechanism has been proposed to be involved in cancer-associated bone pain patients with bone metastases[5]. It has been reported that calcitonin exerts its pain-modulating effect by depressing osteoclasts and correcting the decline in serotonin receptor activity that causes hypoactivity of the descending inhibitory system[7,10,11]. We conducted pain-related behavioral tests and transcriptome analyses in the dorsal root ganglia (DRG) collected from the model rats followed by bioinformatic analyses
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
