Devil’s advocate: Why past and future animal models of neuropathic pain in spinal cord injury are without merit

Most persons living with a spinal cord injury experience neuropathic pain in the months following their lesion, at the moment where they receive intensive gait rehabilitation. Based on studies using animal models, it has been proposed that central sensitization in nociceptive pathways (maladaptive plasticity) and plasticity related to motor learning (adaptive plasticity) share common neural mechanisms and compete with each other. This article aims to address the discrepancy between the growing body of basic science literature supporting this hypothesis and the general belief in rehabilitation research that pain and gait rehabilitation represent two independent problems. First, the main findings from basic research showing interactions between nociception and learning in the spinal cord will be summarized, focusing both on evidence demonstrating the impact of nociception on motor learning and of motor learning on central sensitization. Then, the generalizability of these findings in animal models to humans will be discussed. Finally, the way potential interactions between nociception and motor learning are currently taken into account in clinical research in patients with spinal cord injury will be presented. To conclude, recommendations will be proposed to better integrate findings from basic research into future clinical research in persons with spinal cord injury.

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Faculty Opinions recommendation of Comparison of the effectiveness of amitriptyline and gabapentin on chronic neuropathic pain in persons with spinal cord injury.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1098590.554694 ◽

2007 ◽

Author(s):

Nanna Finnerup

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Neuropathic Pain ◽

Chronic Neuropathic Pain ◽

Cord Injury

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1-kHz high-frequency spinal cord stimulation alleviates chronic refractory pain after spinal cord injury: a case report

JA Clinical Reports ◽

10.1186/s40981-021-00451-x ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Chiaki Yamada ◽

Aiko Maeda ◽

Katsuyuki Matsushita ◽

Shoko Nakayama ◽

Kazuhiro Shirozu ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Neuropathic Pain ◽

Spinal Cord Stimulation ◽

High Frequency ◽

Cervical Vertebrae ◽

Intractable Pain ◽

Target Area ◽

Positive Effects ◽

Cord Injury

Abstract Background Patients with spinal cord injury (SCI) frequently complain of intractable pain that is resistant to conservative treatments. Here, we report the successful application of 1-kHz high-frequency spinal cord stimulation (SCS) in a patient with refractory neuropathic pain secondary to SCI. Case presentation A 69-year-old male diagnosed with SCI (C4 American Spinal Injury Association Impairment Scale A) presented with severe at-level bilateral upper extremity neuropathic pain. Temporary improvement in his symptoms with a nerve block implied peripheral component involvement. The patient received SCS, and though the tip of the leads could not reach the cervical vertebrae, a 1-kHz frequency stimulus relieved the intractable pain. Conclusions SCI-related symptoms may include peripheral components; SCS may have a considerable effect on intractable pain. Even when the SCS electrode lead cannot be positioned in the target area, 1-kHz high-frequency SCS may still produce positive effects.

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Aging and miR-155 in mice influence survival and neuropathic pain after spinal cord injury

Brain Behavior and Immunity ◽

10.1016/j.bbi.2021.07.003 ◽

2021 ◽

Author(s):

Andrew D. Gaudet ◽

Laura K. Fonken ◽

Monica T. Ayala ◽

Steven F. Maier ◽

Linda R. Watkins

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Neuropathic Pain ◽

Cord Injury

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Extracorporeal shockwave therapy in spinal cord injury, early to advance to clinical trials? A systematic review and meta-analysis on animal studies

The Neuroradiology Journal ◽

10.1177/19714009211026899 ◽

2021 ◽

pp. 197140092110268

Author(s):

Seyedeh Niloufar Rafiei Alavi ◽

Arian Madani Neishaboori ◽

Mahmoud Yousefifard

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Clinical Trials ◽

Animal Models ◽

Meta Analysis ◽

Mean Difference ◽

Extracorporeal Shockwave Therapy ◽

Extracorporeal Shockwave ◽

Shockwave Therapy ◽

Cord Injury

Background As there is no consensus over the efficacy of extracorporeal shockwave therapy in the management of spinal cord injury complications, the current meta-analysis aims to investigate preclinical evidence on the matter. Methods The search strategy was developed based on keywords related to ‘spinal cord injury’ and ‘extracorporeal shockwave therapy’. A primary search was conducted in Medline, Embase, Scopus and Web of Science until the end of 2020. Studies which administered extracorporeal shockwave therapy on spinal cord injury animal models and evaluated motor function and/or histological findings were included. The standardised mean difference with a 95% confidence interval (CI) were calculated. Results Seven articles were included. Locomotion was significantly improved in the extracorporeal shockwave therapy treated group (standardised mean difference 1.68, 95% CI 1.05–2.31, P=0.032). It seems that the efficacy of extracorporeal shockwave therapy with an energy flux density of 0.1 mJ/mm2 is higher than 0.04 mJ/mm2 ( P=0.044). Shockwave therapy was found to increase axonal sprouting (standardised mean difference 1.31, 95% CI 0.65, 1.96), vascular endothelial growth factor tissue levels (standardised mean difference 1.36, 95% CI 0.54, 2.18) and cell survival (standardised mean difference 2.49, 95% CI 0.93, 4.04). It also significantly prevents axonal degeneration (standardised mean difference 2.25, 95% CI 1.47, 3.02). Conclusion Extracorporeal shockwave therapy significantly improves locomotor recovery in spinal cord injury animal models through neural tissue regeneration. Nonetheless, in spite of the promising results and clinical application of extracorporeal shockwave therapy in various conditions, current evidence implies that designing clinical trials on extracorporeal shockwave therapy in the management of spinal cord injury may not be soon. Hence, further preclinical studies with the effort to reach the safest and the most efficient treatment protocol are needed.

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