Role of Apolipoprotein E in the tangled mystery of pain

Dhillon, Harjot; Singh, Sargun

doi:10.1016/j.mehy.2018.02.033

Cited by 5 publications

(6 citation statements)

References 82 publications

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“…More concealed is the association between APOE and pain regulation processes [48]. It transports cholesterol into the blood and has many essential functions in the brain, including synaptogenesis, regulating synaptic transmission and promoting nerve regeneration after a nerve injury [49].…”

Section: Discussionmentioning

confidence: 99%

Exploration of candidate serum biomarkers potentially related to the chronic pain condition in Medication–overuse headache

et al. 2019

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Background Medication Overuse Headache (MOH) is a prevalent and disabling disorder resulting from the overuse of analgesic drugs, triptans or other acute headache medications. In previous proteomic studies, several proteins have been found at high concentrations in the urine of MOH patients and in the serum of rats with neuropathic pain. The aim of this study was to compare the serum levels of lipocalin-type Prostaglandin D2 synthase (L-PGDS), Vitamin D-binding protein (VDBP), apolipoprotein E (APOE) and apolipoprotein A1 (APOA1) in MOH patients and healthy individuals, further exploring their relationship with cutaneous pain thresholds (CPTs) in the territories innervated by the trigeminal nerve. Methods Sixty-nine MOH patients and 42 age- and sex-matched healthy volunteers were enrolled in the study. Von Frey-like filaments were applied to the skin territories innervated by the trigeminal nerve, to determine the CPTs. L-PGDS, VDBP, APOE and APOA1 were quantified in the serum by Enzyme-linked Immunosorbent Assay (ELISA). Clinical and laboratory data were collected. Comparisons between MOH patients and healthy individuals were performed using independent t test or χ2 test. To correlate serum proteins with CPTs, Pearson correlation coefficient or Spearman’s rank correlation coefficient were used. Results CPTs were lower among MOH patients. L-PGDS, VDBP and APOE had significantly different serum concentrations between groups (p < 0.01), but no correlation was found with CPTs. APOA1 serum concentrations did not differ between patients and healthy individuals. Conclusions L-PGDS, VDBP and APOE had abnormal serum levels in MOH patients, confirming their alteration in some conditions of chronic headache and neuropathic pain. However, they had no relationship with CPTs. The in-depth study of serum proteins represents a promising approach for a better understanding of MOH, as well as the detection of candidate biomarkers for chronic headache or the risks associated with overuse medications.

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Section: Discussionmentioning

confidence: 99%

Exploration of candidate serum biomarkers potentially related to the chronic pain condition in Medication–overuse headache

et al. 2019

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“…Evidence on apolipoproteins being involved in pain modulation recently increased. 9,10 We and others showed that apolipoprotein A-I (ApoA-I) as well as its structural mimetic peptide D-4F prevent inflammatory pain. 5,11 We revealed that D-4F prevents TRPA1 activation evoked by endogenously occurring OxPL that are generated during inflammation by ROS but not by the exogenous TRPA1 agonist mustard oil (MO).…”

Section: Introductionmentioning

confidence: 99%

D-4F, an ApoA-I mimetic peptide ameliorating TRPA1-mediated nocifensive behaviour in a model of neurogenic inflammation

et al. 2020

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Background: High doses of capsaicin are recommended for the treatment of neuropathic pain. However, low doses evoke mechanical hypersensitivity. Activation of the capsaicin chemosensor transient receptor potential vanilloid 1 (TRPV1) induces neurogenic inflammation. In addition to the release of pro-inflammatory mediators, reactive oxygen species are produced. These highly reactive molecules generate oxidised phospholipids and 4-hydroxynonenal (4-HNE) which then directly activate TRP ankyrin 1 (TRPA1). The apolipoprotein A-I mimetic peptide D-4F neutralises oxidised phospholipids. Here, we asked whether D-4F ameliorates neurogenic hypersensitivity in rodents by targeting reactive oxygen species and 4-HNE in the capsaicin-evoked pain model. Results: Co-application of D-4F ameliorated capsaicin-induced mechanical hypersensitivity and allodynia as well as persistent heat hypersensitivity measured by Randell-Selitto, von Frey and Hargreaves test, respectively. In addition, mechanical hypersensitivity was blocked after co-injection of D-4F with the reactive oxygen species analogue H 2 O 2 or 4-HNE. In vitro studies on dorsal root ganglion neurons and stably transfected cell lines revealed a TRPA1-dependent inhibition of the calcium influx when agonists were pre-incubated with D-4F. The capsaicin-induced calcium influx in TRPV1-expressing cell lines and dorsal root ganglion neurons sustained in the presence of D-4F. Conclusions: D-4F is a promising compound to ameliorate TRPA1-dependent hypersensitivity during neurogenic inflammation.

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“…In the future, interesting advancements in MOH could concern the dosage of vitamin D and MCP-1, together with a re-evaluation of the VDBP protein. More concealed is the association between APOE and the pain regulation process [44]. It transports cholesterol into the blood and has many essential functions in the brain, including synaptogenesis, regulating synaptic transmission and promoting nerve regeneration after a nerve injury [45].…”

Section: Discussionmentioning

confidence: 99%

Exploration of candidate serum biomarkers potentially related to the chronic pain condition in Medication Overuse Headache (MOH)

Pellesi

Bellei

Guerzoni

et al. 2019

Preprint

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Background Medication Overuse Headache (MOH) is a prevalent and disabling disorder resulting from the overuse of analgesic drugs, triptans or other acute headache medications. In previous proteomic studies, several proteins have been found at high concentrations in the urine of MOH patients and in the serum of rats with neuropathic pain. The aim of this study was to compare the serum levels of lipocalin-type Prostaglandin D2 synthase (L-PGDS), Vitamin D-binding protein (VDBP), apolipoprotein E (APOE) and apolipoprotein A1 (APOA1) in MOH patients and healthy individuals, further exploring their relationship with cutaneous pain thresholds (CPTs) in the territories innervated by the trigeminal nerve. Methods 69 MOH patients and 42 age- and sex-matched healthy volunteers were enrolled in the study. Von Frey-like filaments were applied to the skin territories innervated by the trigeminal nerve, to determine the CPTs. L-PGDS, VDBP, APOE and APOA1 were quantified in the serum by Enzyme-linked Immunosorbent Assay (ELISA). Clinical and laboratory data were collected. Comparisons between MOH patients and healthy individuals were performed using independent t test or χ2 test. To correlate serum proteins with CPTs, Pearson correlation coefficient or Spearman's rank correlation coefficient were used. Results CPTs were lower among MOH patients. L-PGDS, VDBP and APOE had significantly different serum concentrations between groups (p < 0.01), but no correlation was found with CPTs. APOA1 serum concentrations did not differ between patients and healthy individuals. Conclusions L-PGDS, VDBP and APOE had abnormal serum levels in MOH patients, confirming their alteration in some conditions of chronic headache and neuropathic pain. The in-depth study of target proteins represents a promising approach for a better understanding of MOH, as well as the detection of candidate biomarkers for chronic headache or the risks associated with overuse medications.

show abstract

Role of Apolipoprotein E in the tangled mystery of pain

Cited by 5 publications

References 82 publications

Exploration of candidate serum biomarkers potentially related to the chronic pain condition in Medication–overuse headache

Exploration of candidate serum biomarkers potentially related to the chronic pain condition in Medication–overuse headache

D-4F, an ApoA-I mimetic peptide ameliorating TRPA1-mediated nocifensive behaviour in a model of neurogenic inflammation

Exploration of candidate serum biomarkers potentially related to the chronic pain condition in Medication Overuse Headache (MOH)

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