From the low-density lipoprotein receptor–related protein 1 to neuropathic pain: a potentially novel target

García-Fernández, Patricia; Üçeyler, Nurcan; Sommer, Claudia

doi:10.1097/pr9.0000000000000898

Cited by 17 publications

(13 citation statements)

References 137 publications

(363 reference statements)

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“…LPR1 has shown to be able to reduce inflammatory response by reducing the production of proinflammatory mediators through different signaling pathways (49). The involvement of LRP1 in FM is unknown, but it is tempting to speculate that the increase in this protein after exercise has a protective role in FM, as it potentially plays a role in modulating and regulating inflammatory response.…”

Section: Discussionmentioning

confidence: 99%

Proteomic Investigation in Plasma from Women with Fibromyalgia in Response to a 15-wk Resistance Exercise Intervention

Wåhlén

Hong

Welinder

et al. 2021

Medicine &Amp; Science in Sports &Amp; Exercise

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Purpose: Fibromyalgia (FM) is a complex pain condition, and exercise is considered the first option of treatment. Few studies have examined the effect of exercise on molecular mechanisms in FM. The aim of this study was to analyze the plasma proteome in women with FM and healthy controls (CON) before and after 15 wk of resistance exercise. This study further investigated whether clinical and exercises-related outcomes correlated with identified plasma proteins in FM. Methods: Plasma samples from 40 FM/25 CON (baseline) and 21 FM/24 CON (postexercise) were analyzed using shotgun proteomics. Clinical/background data were retrieved through questionnaires. Exercise-related variables and pressure pain thresholds were assessed using standardized instruments. Multivariate statistics were applied to analyze the proteomic profile at baseline and postexercise, and correlation with clinical/exercise-related data. Results: Fifteen weeks of resistance exercises improved clinical symptoms and muscle strength, and affected circulating proteins related to immunity, stress, mRNA stability, metabolic processes, and muscle structure development in FM. Pressure pain threshold was related to a specific protein profile, with proteins involved in metabolic and immune response. Subgroups of FM based on plasma proteins, FM duration, and improved muscle strength were identified. Conclusions: Exercise seems to affect circulating proteins, clinical characteristics, and muscle strength in FM. This study contributes to better understanding of systemic protein changes in FM compared with CON and how resistance exercise affects such changes.

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Section: Discussionmentioning

confidence: 99%

Proteomic Investigation in Plasma from Women with Fibromyalgia in Response to a 15-wk Resistance Exercise Intervention

Wåhlén

Hong

Welinder

et al. 2021

Medicine &Amp; Science in Sports &Amp; Exercise

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“…23 Although the loss of LRP1 function appears to promote inflammation and neuropathic pain, it is not known whether the gain of LRP1 activation alleviate nociceptive and neuropathic pain states. 24 Herein, we identify SP16 as a significant regulator of acute nociceptive, inflammatory, and neuropathic pain. SP16 replicated the neurite extension activity previously shown by other LRP1 agonists.…”

Section: Introductionmentioning

confidence: 99%

“…In Schwann cells (SC), genetic deletion of LRP1 increases the extent and magnitude of neuropathic pain before and after injury 23 . Although the loss of LRP1 function appears to promote inflammation and neuropathic pain, it is not known whether the gain of LRP1 activation alleviate nociceptive and neuropathic pain states 24 …”

Section: Introductionmentioning

confidence: 99%

α1‐Antitrypsin derived SP16 peptide demonstrates efficacy in rodent models of acute and neuropathic pain

et al. 2021

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SP16 is an innovative peptide derived from the carboxyl‐terminus of α1‐Antitrypsin (AAT), corresponding to residues 364‐380, and contains recognition sequences for the low‐density lipoprotein receptor‐related protein‐1 (LRP1). LRP1 is an endocytic and cell‐signaling receptor that regulates inflammation. Deletion of Lrp1 in Schwann cells increases neuropathic pain; however, the role of LRP1 activation in nociceptive and neuropathic pain regulation remains unknown. Herein, we show that SP16 is bioactive in sensory neurons in vitro. Neurite length and regenerative gene expression were increased by SP16. In PC12 cells, SP16 activated Akt and ERK1/2 cell‐signaling in an LRP1‐dependent manner. When formalin was injected into mouse hind paws, to model inflammatory pain, SP16 dose‐dependently attenuated nociceptive pain behaviors in the early and late phases. In a second model of acute pain using capsaicin, SP16 significantly reduced paw licking in both male and female mice (p < .01) similarly to enzymatically inactive tissue plasminogen activator, a known LRP1 interactor. SP16 also prevented development of tactile allodynia after partial nerve ligation and this response was sustained for nine days (p < .01). Immunoblot analysis of the injured nerve revealed decreased CD11b (p < .01) and Toll‐like receptor‐4 (p < .005). In injured dorsal root ganglia SP16 reduced CD11b+ cells (p < .05) and GFAP (p < .005), indicating that inflammatory cell recruitment and satellite cell activation were inhibited. In conclusion, administration of SP16 blocked pain‐related responses in three distinct pain models, suggesting efficacy against acute nociceptive, inflammatory, and neuropathic pain. SP16 also attenuated innate immunity in the PNS. These studies identify SP16 as a potentially effective treatment for pain.

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“…It was also shown that activation of LDL receptor-related protein 1 (LRP-1) can indirectly reduce neuropathic pain by attenuation of inflammation, reporting better outcomes for neuropathies such as Alzheimer disease, nerve injury, and diabetic peripheral neuropathy. All these results suggest an extremely interesting therapeutic target of the mechanism of PRF on ZAP [ 22 ].…”

Section: Discussionmentioning

confidence: 99%

Development of a Model for Predicting the Effectiveness of Pulsed Radiofrequency on Zoster-Associated Pain

et al. 2022

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Introduction: Zoster-associated pain (ZAP), which may cause anxiety, depression, and sleep disorders and reduce quality of life, is often refractory to current standard treatments. Studies have shown that pulsed radiofrequency (PRF) can alleviate ZAP and reduce the incidence of postherpetic neuralgia (PHN). This study aimed to explore the clinical characteristics associated with PRF responsiveness, develop a model for identifying risk factors of inadequate PRF management, and help clinicians make better decisions. Methods: Patients who underwent PRF for ZAP between January 2017 and October 2020 in our hospital were included in this study. Patients were evaluated using the numerical rating scale (NRS), Insomnia Severity Index, Patient Health Questionnaire-9, and 36-Item Short Form Health Survey (SF-36) before and 3 months after the procedure. Patient demographic data and blood test results were also collected. We defined the effectiveness of PRF for ZAP as relief of [ 50% in NRS scores compared to pre-PRF. Least absolute shrinkage and selection operator (LASSO) regression analyses were subsequently performed to identify factors related to the therapeutic effect of PRF in patients with ZAP. The performance of the prediction model was assessed by the area under the receiver operating characteristic curve (AUC). Results: The effectiveness of PRF in patients with ZAP was 69.6% (total 313 patients) after 3 months. LASSO regression analysis extracted the seven most powerful features in the developed prediction model: sex, stage of herpes zoster (HZ), pregabalin dose, bodily pain indicators of SF-36, lymphocyte count, and low-density lipoprotein cholesterol (LDLC) and complement C4 in peripheral blood. Model = 1.586 ? 0.148 9 lymphocyte ? (-0.001) 9 bodily pain indicators of SF-36 ? (-0.001) 9 pregabalin dose ? 0.028 9 LDLC ? 0.001 9 C4 ? (-0.508) 9 sex ? (-0.128) 9 stage of HZ. We generated the ROC curve for the prediction model, and the final AUC was 0.701. The sensitivity, specificity, and overall accuracy of the model were 90%, 33%, and 73%, respectively. Conclusions: Seven factors were significantly associated with poor PRF outcome: male sex,

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From the low-density lipoprotein receptor–related protein 1 to neuropathic pain: a potentially novel target

Abstract: The low-density lipoprotein receptor–related protein 1 plays a major role in the regulation of neuroinflammation, neurodegeneration, neuroregeneration, neuropathic pain, and deficient cognitive functions.

Cited by 17 publications

References 137 publications

Proteomic Investigation in Plasma from Women with Fibromyalgia in Response to a 15-wk Resistance Exercise Intervention

Proteomic Investigation in Plasma from Women with Fibromyalgia in Response to a 15-wk Resistance Exercise Intervention

α1‐Antitrypsin derived SP16 peptide demonstrates efficacy in rodent models of acute and neuropathic pain

Development of a Model for Predicting the Effectiveness of Pulsed Radiofrequency on Zoster-Associated Pain

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