Verification of Pain-Related Neuromodulation Mechanisms of Calcitonin in Knee Osteoarthritis

Overview

Journal Mol Neurobiol

Specialties Molecular Biology
Neurology

Date 2025 Feb 24

PMID 39994161

Authors

Qing Lin

Xue Tan

Dezun Ma

Yanfeng Huang

Lili Wang

Danhao Zheng

Jiaqiu Lin

Zaishi Zhu

Min Mao

Zhouping Yi

Jie Wang

Xihai Li

Affiliations

Soon will be listed here.

Abstract

Chronic pain represents the prevailing symptom among patients suffering from knee osteoarthritis (KOA). In KOA, peripheral sensitization is driven by disruptions in subchondral bone homeostasis, local inflammatory responses, and variations in neuropeptide and neurotransmitter levels. Calcitonin, a pivotal peptide involved in bone metabolism, additionally exhibits potent analgesic properties. This study aimed to elucidate the mechanisms underlying calcitonin's neuromodulatory effects related to pain in the treatment of KOA. Three experiments were conducted: (1) assessing calcitonin's therapeutic effects via histomorphology, nociceptive behavioral assessments, and Western blot analysis of proteins; (2) verification of the involvement of neurotransmitters and neuropeptides in calcitonin's action using the Signal Transduction PathwayFinder PCR Array, Bio-Plex suspension chip, and ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS); and (3) exploration of calcitonin's impact on brain function through functional magnetic resonance imaging (fMRI). Experiment 1 validated calcitonin's efficacy in KOA models. Experiment 2 demonstrated the involvement of the retinoic acid signaling pathway in calcitonin treatment, confirming that its analgesic efficacy is associated with the modulation of neuropeptides and neurotransmitters. Experiment 3 revealed that calcitonin treatment could reverse regional homogeneity and amplitude of low-frequency fluctuations in the hippocampus and tegmental nucleus. The study affirmed the critical role of pain-related neuromodulation mechanisms in calcitonin treatment, demonstrating that its analgesic effects are mediated through the modulation of neurotransmitters, neuropeptides, and brain function, as observed via fMRI. These findings provide a theoretical foundation for the clinical application of calcitonin in the treatment of KOA pain.

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