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Contralateral monoarthritis exacerbated chronic constriction injury-induced pain hypersensitivity through upregulating inducible nitric oxide synthase

Authors Zhao H, Liu S, Wang C, Wang Q, Liu W, Gong M

Received 1 March 2018

Accepted for publication 4 May 2018

Published 1 August 2018 Volume 2018:11 Pages 1433—1443

DOI https://doi.org/10.2147/JPR.S166994

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Justinn Cochran

Peer reviewer comments 2

Editor who approved publication: Dr Michael E Schatman


Heng Zhao,1 Shenghou Liu,1 Chenhua Wang,2 Qingjie Wang,3 Wenguang Liu,1 Mingzhi Gong1

1Department of Orthopedics, The Second Hospital of Shandong University, Jinan, 250033, Shandong, People’s Republic of China; 2Department of Nuclear Medicine, The Second Hospital of Shandong University, Jinan, 250033, Shandong, People’s Republic of China; 3Department of Emergency, The Second Hospital of Shandong University, Jinan, 250033, Shandong, People’s Republic of China

Introduction: High comorbidity of osteoarthritis (OA) and neuropathic pain has been reported in aged patients. Evidence shows that central sensitization of pain processing occurs in late-phase OA and may facilitate the development of neuropathic pain. Few studies reveal whether acute monoarthritis (MA) aggravates neuropathic pain on the opposite side of the body from the injury.
Methods: To address whether neuropathic pain is affected by contralateral MA through distinct inflammatory pathway, MA was induced by intra-articular injection of complete Freund’s adjuvant (CFA) into the right tibiotarsal joint, and neuropathic pain was established by chronic constriction injury (CCI) of the left sciatic nerve.
Results: We observed that MA aggravated mechanical allodynia and thermal hyperalgesia in CCI rats. Furthermore, MA affected the other side of the spinal cord in multiple aspects, including the upregulation of iNOS mRNA and the enhancement of forskolin-induced facilitation of excitatory synaptic transmission in the spinal cord dorsal horn substantia gelatinosa neurons.
Discussion: Interestingly, intrathecal injection of 1400W, an antagonist of iNOS, attenuated intensity of pain behaviors in CCI rats with contralateral MA to similar levels in CCI rats without MA, and also normalized the facilitatory effect of forskolin on excitatory synaptic transmission in the spinal cord dorsal horn neurons in contralateral MA rats. Therefore, contralateral MA worsened CCI-induced pain hypersensitivity probably through upregulating iNOS and enhancing the facilitation of synaptic transmission following CCI.
Conclusion: Inhibiting the iNOS might be a potential therapeutic strategy for concurrent OA and neuropathic pain.

Keywords: osteoarthritis, neuropathic pain, acute monoarthritis, chronic constriction injury

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