Identifying neuropathic pain in patients with multiple sclerosis: a cross-sectional multicenter study using highly specific criteria

Solaro, Claudio; Cella, Matteo; Signori, Alessio; Martinelli, Vittorio; Radaelli, Marta; Centonze, Diego; Sica, Francesco; Grasso, Maria Grazia; Clemenzi, Alessandro; Bonavita, Simona; Esposito, Sabrina; Patti, Francesco; D’Amico, Emanuele; Cruccu, G.; Truini, Andrea

doi:10.1007/s00415-018-8758-2

Cited by 51 publications

(72 citation statements)

References 23 publications

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“…2F, G). Hence, phosphorylation of eIF2α, as measured by the ratio of p-eIF2α to t-eIF2α, was found to be increased at the chronic timepoint (F p-eIF2α/t-eIF2α (2,9)=12.75, p=0.0024; One-way ANOVA) ( Fig. 2H).…”

Section: Er Stress In the Drg Of Eae Micementioning

confidence: 89%

“…We next assessed the expression of ER proteins in the DRG of mice with EAE over the course of the disease. The levels of BiP, a luminal ER chaperone, were elevated in the DRG at the chronic stage of the disease (F BiP (2,9)=7.950, p=0.0103, One-way ANOVA) ( Fig. 2E).…”

Section: Er Stress In the Drg Of Eae Micementioning

confidence: 95%

“…2H). Interestingly, levels of the UPR transcription factors XBP1 and CHOP were upregulated at disease onset and remained elevated into the chronic phase (F XBP1 (2,9)=18.59, p=0.0006; F CHOP (2,9)=12.08, p=0.0028, One-way ANOVA) ( Fig. 2I, J).…”

Section: Er Stress In the Drg Of Eae Micementioning

confidence: 96%

“…2E). Levels of phosphorylated eIF2α (p-eIF2α) were significantly upregulated at the chronic time point whereas total eIF2α (t-eIF2α) levels only trended toward an increase with the progression of disease (F t-eIF2α (2,9)=3.808, p=0.0633, F p-eIF2α (2,9)=7.030, p=0.0145; One-way ANOVA) ( Fig. 2F, G).…”

Section: Er Stress In the Drg Of Eae Micementioning

confidence: 98%

“…Among the many sensory abnormalities associated with MS, pain is common and often debilitating. Pain is experienced by one third to a half of the population with MS at some point during their disease course and a significant percentage are diagnosed with neuropathic pain (1,2). Current pharmacological approaches to alleviate this pain have been largely ineffective with low patient confidence in prevailing treatment approaches (3).…”

Section: Introductionmentioning

confidence: 99%

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ER stress-mediated BK dysfunction in the DRG underlies pain in a model of multiple sclerosis

Yousuf¹,

Samtleben²,

Lamothe

et al. 2020

Preprint

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AcknowledgementsWe would like to thank Drs. Simonetta Sipione, Christine Webber, and Jason Plemel (University of Alberta) for graciously sharing select equipment and software. ABSTRACTNeuropathic pain is a common symptom of multiple sclerosis (MS) and current treatment options are ineffective. In this study, we investigated whether endoplasmic reticulum (ER) stress in dorsal root ganglia (DRG) contributes to pain hypersensitivity in the experimental autoimmune encephalomyelitis (EAE) mouse model of MS. Inflammatory cells and increased levels of ER stress markers are evident in post-mortem DRGs from MS patients. Similarly, we observed ER stress in the DRG of mice with EAE and relieving ER stress with a chemical chaperone, 4phenylbutyric acid (4-PBA), reduced pain hypersensitivity. In vitro, 4-PBA and the selective PERK inhibitor, AMG44, normalize cytosolic Ca 2+ transients in putative DRG nociceptors. We went to assess disease-mediated changes in the functional properties of Ca 2+ -sensitive BK-type K + channels in DRG neurons. We found that the conductance-voltage (GV) relationship of BK channels was shifted to a more positive voltage, together with a more depolarized resting membrane potential in EAE cells. Our results suggest that ER stress in sensory neurons of MS patients and mice with EAE is a source of pain and that ER stress modulators can effectively counteract this phenotype.

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Section: Er Stress In the Drg Of Eae Micementioning

confidence: 89%

Section: Er Stress In the Drg Of Eae Micementioning

confidence: 95%

Section: Er Stress In the Drg Of Eae Micementioning

confidence: 96%

Section: Er Stress In the Drg Of Eae Micementioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

ER stress-mediated BK dysfunction in the DRG underlies pain in a model of multiple sclerosis

Yousuf¹,

Samtleben²,

Lamothe

et al. 2020

Preprint

View full text Add to dashboard Cite

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Sensory and pain modulation profiles of ongoing central neuropathic extremity pain in multiple sclerosis

Šrotová

Kočica

Vollert

et al. 2020

European Journal of Pain

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Background Central neuropathic extremity pain (CNEP) is the most frequent type of pain in multiple sclerosis (MS). The aim of the present study was to evaluate sensory and pain modulation profiles in MS patients with CNEP. Methods In a single‐centre observational study, a group of 56 CNEP MS patients was compared with 63 pain‐free MS patients and with a sex‐ and age‐adjusted control group. Standardized quantitative sensory testing (QST) and dynamic QST (dQST) protocols comprising temporal summation and conditioned pain modulation tests were used to compare sensory profiles. Results Loss‐type QST abnormalities in both thermal and mechanical QST modalities prevailed in both MS subgroups and correlated significantly with higher degree of disability expressed as Expanded Disability Status Scale (EDSS). Comparison of sensory phenotypes disclosed a higher frequency of the ‘sensory loss’ prototypic sensory phenotype in the CNEP subgroup (30%) compared with pain‐free MS patients (6%; p = .003). Conclusion The role of aging process and higher lesion load in the spinothalamocortical pathway might be possible explanation for pain development in this particular ‘deafferentation’ subtype of central neuropathic pain in MS. We were unable to support the role of central sensitization or endogenous facilitatory and inhibitory mechanisms in the development of CNEP in MS. Significance This article presents higher prevalence of the ‘sensory loss’ prototypic sensory phenotype in multiple sclerosis patients with central extremity neuropathic pain compared to pain‐free patients. Higher degree of disability underlines the possible role of higher lesion load in the somatosensory pathways in this particular ‘deafferentation’ type of central neuropathic pain.

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Development and external validation of multivariable risk models to predict incident and resolved neuropathic pain: a DOLORisk Dundee study

et al. 2022

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Neuropathic pain is difficult to treat, and an understanding of the risk factors for its onset and resolution is warranted. This study aimed to develop and externally validate two clinical risk models to predict onset and resolution of chronic neuropathic pain. Participants of Generation Scotland: Scottish Family Health Study (GS; general Scottish population; n = 20,221) and Genetic of Diabetes Audit and Research in Tayside Scotland (GoDARTS; n = 5236) were sent a questionnaire on neuropathic pain and followed- -up 18 months later. Chronic neuropathic pain was defined using DN4 scores (≥ 3/7) and pain for 3 months or more. The models were developed in GS using logistic regression with backward elimination based on the Akaike information criterion. External validation was conducted in GoDARTS and assessed model discrimination (ROC and Precision-Recall curves), calibration and clinical utility (decision curve analysis [DCA]). Analysis revealed incidences of neuropathic pain onset (6.0% in GS [236/3903] and 10.7% in GoDARTS [61/571]) and resolution (42.6% in GS [230/540] and 23.7% in GoDARTS [56/236]). Psychosocial and lifestyle factors were included in both onset and resolved prediction models. In GoDARTS, these models showed adequate discrimination (ROC = 0.636 and 0.699), but there was evidence of miscalibration (Intercept = − 0.511 and − 0.424; slope = 0.623 and 0.999). The DCA indicated that the models would provide clinical benefit over a range of possible risk thresholds. To our knowledge, these are the first externally validated risk models for neuropathic pain. The findings are of interest to patients and clinicians in the community, who may take preventative or remedial measures.

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Identifying neuropathic pain in patients with multiple sclerosis: a cross-sectional multicenter study using highly specific criteria

Cited by 51 publications

References 23 publications

ER stress-mediated BK dysfunction in the DRG underlies pain in a model of multiple sclerosis

ER stress-mediated BK dysfunction in the DRG underlies pain in a model of multiple sclerosis

Sensory and pain modulation profiles of ongoing central neuropathic extremity pain in multiple sclerosis

Development and external validation of multivariable risk models to predict incident and resolved neuropathic pain: a DOLORisk Dundee study

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