Recent advances in understanding neuropathic pain: glia, sex differences, and epigenetics

Machelska, Halina; Celik, Melih Ö.

doi:10.12688/f1000research.9621.1

Cited by 44 publications

(43 citation statements)

References 95 publications

(141 reference statements)

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“…ASA, acetylsalicylic acid; CYP, cytochrome P450; CGRP, calcitonin gene-related peptide; GI, gastrointestinal; NMDA, N-methyl-D-aspartate. a role in sex-related differences in migraine and its treatment (Machelska and Celik, 2016).…”

Section: Potential Mechanisms Of Sex-related Responses To Pharmacothementioning

confidence: 99%

Sex-Specific Pharmacotherapy for Migraine: A Narrative Review

Gazerani

Cairns

2020

Front. Neurosci.

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Migraine is a common neurological disorder characterized by recurrent headache episodes that accompany sensory-motor disturbances, such as higher sensitivity to touch and light, extremity heaviness or weakness, and speech or language disabilities. Worldwide, migraine is one of the top 10 causes of disability and hence poses a huge economic burden to society. On average, migraine occurs in 12% of population but its occurrence is sexually dimorphic, as it is two to three times more prevalent in women than in men. This female to male ratio of migraine prevalence is age-and sex hormone-dependent. Advancements in understanding migraine pathogenesis have also revealed an association with both genetics and epigenetics. The severity of migraine, in terms of its attack duration, headache intensity, frequency, and occurrence of migraineassociated symptoms, has generally been reported to be greater in women. Sex differences in migraine disability and comorbidities, such as psychiatric disorders, have also been noted in some population-based studies. However, research on sex-related differences in response to migraine treatments is relatively scarce. Although a general observation is that women consume more medication than men for migraine treatment, strategies for the use of abortive and preventive medications for migraine are generally similar in both sexes. This narrative review summarizes available findings on sexually distinct responses to abortive and prophylactic pharmacotherapy of migraine. Basic experimental data and clinical findings will be presented, and potential mechanisms underlying sex-based responses will be discussed to highlight the importance and value of sex-based treatment in migraine research and practice.

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Section: Potential Mechanisms Of Sex-related Responses To Pharmacothementioning

confidence: 99%

Sex-Specific Pharmacotherapy for Migraine: A Narrative Review

Gazerani

Cairns

2020

Front. Neurosci.

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“…The mechanisms of pathological pain are complex and characterized by both peripheral and central neuronal alterations and neuroimmune activation, which modulates in the initiation and maintenance of chronic pain. Glial cells, including microglia, astrocytes, and oligodendrocytes, located within the central nervous system (CNS), as well as Schwann cells located in the peripheral nervous system (PNS), modulate inflammation after nerve injury (Machelska and Celik, 2016). Following injury, neuronal inflammation and reparatory mechanisms of neural tissues induce a state of peripheral hyperexcitability in primary afferent nociceptors.…”

Section: Introductionmentioning

confidence: 99%

The Endogenous Cannabinoid System: A Budding Source of Targets for Treating Inflammatory and Neuropathic Pain

Donvito

Nass

Wilkerson

et al. 2017

Neuropsychopharmacol.

222

168

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A great need exists for the development of new medications to treat pain resulting from various disease states and types of injury. Given that the endogenous cannabinoid (that is, endocannabinoid) system modulates neuronal and immune cell function, both of which play key roles in pain, therapeutics targeting this system hold promise as novel analgesics. Potential therapeutic targets include the cannabinoid receptors, type 1 and 2, as well as biosynthetic and catabolic enzymes of the endocannabinoids N-arachidonoylethanolamine and 2-arachidonoylglycerol. Notably, cannabinoid receptor agonists as well as inhibitors of endocannabinoid-regulating enzymes fatty acid amide hydrolase and monoacylglycerol lipase produce reliable antinociceptive effects, and offer opioid-sparing antinociceptive effects in myriad preclinical inflammatory and neuropathic pain models. Emerging clinical studies show that 'medicinal' cannabis or cannabinoid-based medications relieve pain in human diseases such as cancer, multiple sclerosis, and fibromyalgia. However, clinical data have yet to demonstrate the analgesic efficacy of inhibitors of endocannabinoid-regulating enzymes. Likewise, the question of whether pharmacotherapies aimed at the endocannabinoid system promote opioid-sparing effects in the treatment of pain reflects an important area of research. Here we examine the preclinical and clinical evidence of various endocannabinoid system targets as potential therapeutic strategies for inflammatory and neuropathic pain conditions.

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“…Role of N-Acylethanolamines in the Neuroinflammation: Ultramicronized Palmitoylethanolamide in the Relief of Chronic Pain and Neurodegenerative Diseases IL-33 at spinal levels contributes to a further release of proinflammatory cytokines such as TNF-α and IL-1β [34]. Another important role in neuroinflammation at the base of chronic pain appears to be mediated by mast cells, which represent the signaling link between peripheral inflammation and the brain.…”

Section: Reviewmentioning

confidence: 99%

Role of N-Acylethanolamines in the Neuroinflammation: Ultramicronized Palmitoylethanolamide in the Relief of Chronic Pain and Neurodegenerative DiseasesRole of N-Acylethanolamines in the Neuroinflammation: Ultramicronized Palmitoylethanolamide in the Relief of Chronic Pain and Neurodegenerative Diseases

Palazzo¹,

Luongo²,

Guida³

et al. 2019

Neuropsychiatry

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Pain and neuroinflammation are protective responses aimed at preventing and removing injurious stimuli. However, when prolonged, they can override the bounds of physiological control and become destructive. Chronic pain and neuroinflammation are critical components in the pathophysiology of neurodegenerative diseases, stroke, spinal cord injury, diabetes, and neuropsychiatric disorders. Natural mechanisms, including the production of lipid mediators, represent an endogenous protective process and a program of resolution stimulated and triggered by tissue injury or inflammation. Lipid mediators include N-acylethanolamines (NAEs) such as palmitoylethanolamide (PEA), an endocannabinoid anandamide congener which has shown to be endowed of neuroprotective and antinflammatory properties activated under several pathological states. PEA does not bind the classical cannabinoid receptors but indirectly stimulates the effects of cannabinoids. Its antinflammatory, analgesic and neuroprotective actions have been however associated with peroxisome proliferator-activated receptor-α (PPAR-α) activation. The administration of exogenous PEA requires parenteral routes owing to its lipid structure. The micronized and ultramicronized (m-and um-) formulation permits oral administration increasing the versatility, easiness and compliance of administrations in clinical studies. This review is intended to deal with the effects of m-and um-PEA on chronic pain and neuroinflammation in several animal models of chronic pain and neudegenerative disorders and in clinical studies.

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Recent advances in understanding neuropathic pain: glia, sex differences, and epigenetics

Cited by 44 publications

References 95 publications

Sex-Specific Pharmacotherapy for Migraine: A Narrative Review

Sex-Specific Pharmacotherapy for Migraine: A Narrative Review

The Endogenous Cannabinoid System: A Budding Source of Targets for Treating Inflammatory and Neuropathic Pain

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