Chronic pain is common in mitochondrial disease

Ameele, Jelle van den; Fuge, Joshua; Pitceathly, Robert D S; Berry, Sarah; McIntyre, Zoe; Hanna, Michael G.; Lee, Michael C.; Chinnery, Patrick F.

doi:10.1016/j.nmd.2020.02.017

Cited by 30 publications

(21 citation statements)

References 16 publications

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“…The m.3243A > G MTTL1 mutation patients showed higher pain severity and higher possibility of neuropathic pain compared to other causative mtDNA and nuclear DNA mutations. 18 Smeitink J et al 19 proposed that the disentangling of the angiopathy paradigm, ROS-redox metabolism, or ROS-induced inflammation pathways might be the mechanisms of mitochondrial migraine. In the study from The Newcastle Group, 12 migraine related to m.3243A>G mutation showed a moderate correlation with gastrointestinal dysfunction (r~0.45).…”

Section: Headache and Migrainementioning

confidence: 99%

The non-syndromic clinical spectrums of mtDNA 3243A>G mutation

Shen

2021

NSJ

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The m.3243A >G mutation in the tRNA Leu )UUR( gene )MT-TL1( of the mitochondrial DNA is the most widely seen pathogenic mtDNA mutation which has major phenotypic variations. The clinical phenotype involves various organs such as the brain and nerves, skeletal muscles, heart, endocrine system, gastrointestinal tract, and skin. Some phenotypes conform to well established syndromes, while most of the symptoms appear individually or concomitant to other syndromes, making identification difficult. Furthermore, some progress has been made on cardiac manifestations as well as complications during pregnancy and perinatal period. This article provides a systematic review of the non-syndromic phenotypes and latest developments in m.3243A>G mutation.

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Section: Headache and Migrainementioning

confidence: 99%

The non-syndromic clinical spectrums of mtDNA 3243A>G mutation

Shen

2021

NSJ

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“…As chronic pain is common in patients with different mitochondrial diseases [115], it would be helpful to know whether metabolic alterations directly interact with nociception and pain in FM or whether these metabolic alterations reflect other mitochondrial mechanisms more directly associated with nociception and pain. For example, increased lactate and pyruvate levels can induce ROS, which in turn may interact with nociception [116][117][118][119].…”

Section: Multivariate Associations Between Pain Aspects and Spectroscopy And MD Variablesmentioning

confidence: 99%

Evidence of Mitochondrial Dysfunction in Fibromyalgia: Deviating Muscle Energy Metabolism Detected Using Microdialysis and Magnetic Resonance

Gerdle

Ghafouri

Lund

et al. 2020

JCM

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In fibromyalgia (FM) muscle metabolism, studies are sparse and conflicting associations have been found between muscle metabolism and pain aspects. This study compared alterations in metabolic substances and blood flow in erector spinae and trapezius of FM patients and healthy controls. FM patients (n = 33) and healthy controls (n = 31) underwent a clinical examination that included pressure pain thresholds and physical tests, completion of a health questionnaire, participation in microdialysis investigations of the etrapezius and erector spinae muscles, and also underwent phosphorus-31 magnetic resonance spectroscopy of the erector spinae muscle. At the baseline, FM had significantly higher levels of pyruvate in both muscles. Significantly lower concentrations of phosphocreatine (PCr) and nucleotide triphosphate (mainly adenosine triphosphate) in erector spinae were found in FM. Blood flow in erector spinae was significantly lower in FM. Significant associations between metabolic variables and pain aspects (pain intensity and pressure pain threshold PPT) were found in FM. Our results suggest that FM has mitochondrial dysfunction, although it is unclear whether inactivity, obesity, aging, and pain are causes of, the results of, or coincidental to the mitochondrial dysfunction. The significant regressions of pain intensity and PPT in FM agree with other studies reporting associations between peripheral biological factors and pain aspects.

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“…This idea is bolstered by more recent studies which found mitochondrial dysfunction in animal models of chronic pain and patients with chronic pain [119]. A recent 2020 review summarized results which show that although chronic pain was not considered a core symptom in persons with mitochondrial disease, it is a commonly observed clinical symptom [120].…”

Section: Mitochondria Function and Painmentioning

confidence: 99%

Soluble Epoxide Hydrolase Regulation of Lipid Mediators Limits Pain

et al. 2020

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The role of lipids in pain signaling is well established and built on decades of knowledge about the pain and inflammation produced by prostaglandin and leukotriene metabolites of cyclooxygenase and lipoxygenase metabolism, respectively. The analgesic properties of other lipid metabolites are more recently coming to light. Lipid metabolites have been observed to act directly at ion channels and G protein-coupled receptors on nociceptive neurons as well as act indirectly at cellular membranes. Cytochrome P450 metabolism of specifically long-chain fatty acids forms epoxide metabolites, the epoxy-fatty acids (EpFA). The biological role of these metabolites has been found to mediate analgesia in several types of pain pathology. EpFA act through a variety of direct and indirect mechanisms to limit pain and inflammation including nuclear receptor agonism, limiting endoplasmic reticulum stress and blocking mitochondrial dysfunction. Small molecule inhibitors of the soluble epoxide hydrolase can stabilize the EpFA in vivo, and this approach has demonstrated relief in preclinical modeled pain pathology. Moreover, the ability to block neuroinflammation extends the potential benefit of targeting soluble epoxide hydrolase to maintain EpFA for neuroprotection in neurodegenerative disease.

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Chronic pain is common in mitochondrial disease

Cited by 30 publications

References 16 publications

The non-syndromic clinical spectrums of mtDNA 3243A>G mutation

The non-syndromic clinical spectrums of mtDNA 3243A>G mutation

Evidence of Mitochondrial Dysfunction in Fibromyalgia: Deviating Muscle Energy Metabolism Detected Using Microdialysis and Magnetic Resonance

Soluble Epoxide Hydrolase Regulation of Lipid Mediators Limits Pain

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