Progression of Neuropathic Pain after Acute Spinal Cord Injury: A Meta-Analysis and Framework for Clinical Trials

Warner, Freda M.; Cragg, Jacquelyn J.; Jutzeler, Catherine R.; Finnerup, Nanna Brix; Werhagen, Lars; Weidner, Norbert; Maier, Doris; Kalke, Yorck-Bernhard; Curt, Armin; Kramer, John L. K.

doi:10.1089/neu.2018.5960

Cited by 38 publications

(39 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Of the 16 patients that reported neuropathic pain at Discharge, 13 already exhibited neuropathic pain at Admission, that is, in the first 2 months postinjury. This differential pattern of evolution between MSK and neuropathic pain in the first 6 to 12 months postinjury is consistent with previous studies, 15 , 38 - 40 supporting the external validity of the results despite the limited sample size.…”

Section: Discussionsupporting

confidence: 91%

See 1 more Smart Citation

Conditioned Pain Modulation Decreases Over Time in Patients With Neuropathic Pain Following a Spinal Cord Injury

Gagné

Côté

Boulet

et al. 2020

Neurorehabil Neural Repair

Self Cite

View full text Add to dashboard Cite

Background Neuropathic pain is a major problem following spinal cord injury (SCI). Central mechanisms involved in the modulation of nociceptive signals have been shown to be altered at the chronic stage, and it has been hypothesized that they might play a role in the development of chronic pain. Objective This prospective longitudinal study aimed to describe the evolution of pain modulation mechanisms over time after SCI, and to explore the relationships with the presence of clinical (neuropathic and musculoskeletal) pain. Methods Patients with an SCI were assessed on admission (n = 35; average of 38 days postinjury) and discharge (n = 25; average of 131 days postinjury) using the International Spinal Cord Injury Pain Basic Data Set. Conditioned pain modulation was assessed using the cold pressor test (10 °C; 120 s) as the conditioning stimulus and tonic heat pain, applied above the level of injury, as the test stimulus (120 s). Heat pain threshold was also assessed. Results A marked decrease in the efficacy of conditioned pain modulation was observed over time, with 30.2% of inhibition at admission and only 12.9% at discharge on average ( P = .010). This decrease was observed only in patients already suffering from neuropathic pain at admission and was not explained by a general increase in sensitivity to thermal nociceptive stimuli. Conclusion These results suggest that the presence of neuropathic pain leads to a decrease in conditioned pain modulation over time, rather than supporting the hypothesis that inefficient conditioned pain modulation mechanisms are leading to the development of neuropathic pain.

show abstract

Section: Discussionsupporting

confidence: 91%

“…As previously reported in the months following SCI, at-level neuropathic pain was the most prevalent type of neuropathic pain. 15 , 38 , 39 Among the 24 patients with MSK pain measures available at admission and discharge: 19 patients had MSK pain >1/10 at Admission, and 13 patients had pain at Discharge.…”

Section: Resultsmentioning

confidence: 99%

Conditioned Pain Modulation Decreases Over Time in Patients With Neuropathic Pain Following a Spinal Cord Injury

Gagné

Côté

Boulet

et al. 2020

Neurorehabil Neural Repair

Self Cite

View full text Add to dashboard Cite

show abstract

“…An estimate upwards of 80% of patients following SCI may develop CNP, and the symptom progression of CNP secondary to SCI has been studied in depth. A meta-analysis of the symptom transition period (1–6 months and 1–12 months post-injury) showed that in patients with initial pain 1 month after injury, 72% had persistent symptoms at 6 months post-injury and 69% had persistent pain at 12 months post-injury [ 14 ]. Regression analysis showed that older age increased the likelihood of developing neuropathic pain [ 14 ].…”

Section: Epidemiologymentioning

confidence: 99%

“…A meta-analysis of the symptom transition period (1–6 months and 1–12 months post-injury) showed that in patients with initial pain 1 month after injury, 72% had persistent symptoms at 6 months post-injury and 69% had persistent pain at 12 months post-injury [ 14 ]. Regression analysis showed that older age increased the likelihood of developing neuropathic pain [ 14 ]. A recent prospective study assessing predictors of pain following SCI showed that neuropathic pain increased with time while musculoskeletal pain decreased [ 15 ].…”

Section: Epidemiologymentioning

confidence: 99%

See 1 more Smart Citation

Central Neuropathic Mechanisms in Pain Signaling Pathways: Current Evidence and Recommendations

et al. 2020

View full text Add to dashboard Cite

Purpose This is a comprehensive review of the current literature on central neuropathic pain mechanisms that is secondary to spinal cord injury. It reviews recent and seminal findings on the pathophysiology, diagnosis, and treatment and compares treatment options and recommendations. Recent Findings Neuropathic pain (NP) is a common complication of spinal cord injury (SCI). Chronicity of NP is attributed to increased abundance of inflammatory mediators and ion channel dysfunction leading to afferent nerve sensitization; nerve damage and nerve–glia cross talk have also been implicated. Conventional treatment is medical and has had limited success. Recent studies have made headway in identifying novel biomarkers, including microRNA and psychosocial attributes that can predict progress from SCI to chronic NP (CNP). Recent advances have provided evidence of efficacy for two promising drugs. Baclofen was able to provide good, long-lasting pain relief. Ziconotide, a voltage-gated calcium channel blocker, was studied in a small trial and was able to provide good analgesia in most participants. However, several participants had to be withdrawn because of worrisome creatine phosphokinase (CPK) elevations, and further studies are required to define its safety profile. Non-medical interventions include brain sensitization and biofeedback techniques. These methods have recently had encouraging results, albeit preliminary. Case reports of non-conventional techniques, such as hypnosis, were also reported. Summary CNP is a common complication of SCI and is a prevalent disorder with significant morbidity and disability. Conventional medical treatment is limited in efficacy. Recent studies identified baclofen and ziconotide as possible new therapies, alongside non-medical interventions. Further research into the pathophysiology is required to identify further therapy candidates. A multidisciplinary approach, including psychosocial support, medical and non-medical interventions, is likely needed to achieve therapeutic effects in this difficult to treat syndrome.

show abstract

Multifunctional Integrated Nanozymes Facilitate Spinal Cord Regeneration by Remodeling the Extrinsic Neural Environment

et al. 2023

View full text Add to dashboard Cite

High levels of reactive oxygen species (ROS) and inflammation create a complicated extrinsic neural environment that dominates the initial post‐injury period after spinal cord injury (SCI). The compensatory pathways between ROS and inflammation limited the efficacy of modulating the above single treatment regimen after SCI. Here, novel “nanoflower” Mn3O4 integrated with “pollen” IRF‐5SiRNA was designed as a combination antioxidant and anti‐inflammatory treatment after SCI. The “nanoflower” and “pollen” structure was encapsulated with a neutrophil membrane for protective and targeted delivery. Furthermore, valence‐engineered nanozyme Mn3O4 imitated the cascade response of antioxidant enzymes with a higher substrate affinity compared to natural antioxidant enzymes. Nanozymes effectively catalyzed ROS to generate O2, which is advantageous for reducing oxidative stress and promoting angiogenesis. The screened “pollen” IRF‐5SiRNA could reverse the inflammatory phenotype by reducing interferon regulatory factors‐5 (IRF‐5) expression (protein level: 73.08% and mRNA level: 63.10%). The decreased expression of pro‐inflammatory factors reduced the infiltration of inflammatory cells, resulting in less neural scarring. In SCI rats, multifunctional nanozymes enhanced the proliferation of various neuronal subtypes (motor neurons, interneurons, and sensory neurons) and the recovery of locomotor function, demonstrating that the remodeling of the extrinsic neural environment is a promising strategy to facilitate nerve regeneration.

show abstract

Progression of Neuropathic Pain after Acute Spinal Cord Injury: A Meta-Analysis and Framework for Clinical Trials

Cited by 38 publications

References 33 publications

Conditioned Pain Modulation Decreases Over Time in Patients With Neuropathic Pain Following a Spinal Cord Injury

Conditioned Pain Modulation Decreases Over Time in Patients With Neuropathic Pain Following a Spinal Cord Injury

Central Neuropathic Mechanisms in Pain Signaling Pathways: Current Evidence and Recommendations

Multifunctional Integrated Nanozymes Facilitate Spinal Cord Regeneration by Remodeling the Extrinsic Neural Environment

Contact Info

Product

Resources

About