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Involvement of Oxidative Stress and Nerve Growth Factor in Behavioral and Biochemical Deficits of Experimentally Induced Musculoskeletal Pain in Mice: Ameliorative Effects of Heraclin

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Abstract

Musculoskeletal pain is a widespread complex regional pain syndrome associated with altered emotional and cognitive functioning along with heightened physical disability that has become a global health concern. Effective management of this disorder and associated disabilities includes accurate diagnosis of its biomarkers and instituting mechanism–based therapeutic interventions. Herein, we explored the role of heraclin, a plant-derived molecule, in musculoskeletal pain and its underlying mechanistic approaches in an experimental mouse model. Reserpine (0.5 mg/kg) for 3 consecutive days evoked hyperalgesia, motor incoordination, lack of exploratory behavior, anxiety, and cognition lapse in mice. Reserpine-challenged mice displayed higher serum cytokine level, altered brain neurotransmitter content, elevated brain and muscle oxidative stress, and upregulated brain nerve growth factor receptor expression. Treatment with heraclin (10 mg/kg for 5 consecutive days) exerted analgesic effect and improved motor coordination and memory deficits in mice. Heraclin arrested serum cytokine rise, normalized brain neurotransmitter content, reduced tissue oxidative stress, and downregulated the nerve growth factor receptor expression. Therefore, it may be suggested that heraclin exerts beneficial effects against reserpine-induced musculoskeletal pain disorder possibly through the attenuation of NGFR-mediated pain and inflammatory signaling.

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Funding

Rajbir Bhatti received grant from Department of Science and technology (DST), India, under DST-SERB scheme (EMR/2016/005878), DST-Purse scheme and UGC-RUSA scheme. Anudeep Kaur received fellowship grant from University grants commission (UGC) under Maulana Azad National Fellowship (UGC-MANF) scheme (Award no F1-17.1/201718/MANF-2017-18-PUN-84339).

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Rajbir Bhatti designed the study hypothesis and conceptualized the work. Anudeep Kaur performed the animal studies. Lovedeep Singh and Harmanpreet Kaur performed histological experiments. Nirmal Singh assisted in statistical analyses of results. Saweta Garg helped in animal studies.

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Correspondence to Rajbir Bhatti.

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Kaur, A., Singh, L., Garg, S. et al. Involvement of Oxidative Stress and Nerve Growth Factor in Behavioral and Biochemical Deficits of Experimentally Induced Musculoskeletal Pain in Mice: Ameliorative Effects of Heraclin. J Mol Neurosci 71, 347–357 (2021). https://doi.org/10.1007/s12031-020-01656-y

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  • DOI: https://doi.org/10.1007/s12031-020-01656-y

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