The Physiological Action of Cholesterol

Cashin, Martin F.; Morávek, Vladimír

doi:10.1152/ajplegacy.1927.82.2.294

Cited by 48 publications

(11 citation statements)

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“…Subsequent to the finding that neurosteroids produce anesthesia in rat models and thus suppress pain sensation [252][253][254], neurosteroids have been found to promote analgesia [251,255], and have documented efficacy in the treatment of neuropathic pain [145]. Whereas lower levels of testosterone or progesterone have been associated with low nociceptive thresholds, injecting these steroidal hormones has been found to elicit analgesia [251,[256][257][258][259][260].…”

Section: Neurosteroidsmentioning

confidence: 99%

Targeting Opioid-Induced Hyperalgesia in Clinical Treatment: Neurobiological Considerations

et al. 2015

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Opioid analgesics have become a cornerstone in the treatment of moderate to severe pain, resulting in a steady rise of opioid prescriptions. Subsequently, there has been a striking increase in the number of opioid-dependent individuals, opioid-related overdoses, and fatalities. Clinical use of opioids is further complicated by an increasingly deleterious profile of side effects beyond addiction, including tolerance and opioid-induced hyperalgesia (OIH), where OIH is defined as an increased sensitivity to already painful stimuli. This paradoxical state of increased nociception results from acute and long-term exposure to opioids, and appears to develop in a substantial subset of patients using opioids. Recently, there has been considerable interest in developing an efficacious treatment regimen for acute and chronic pain. However, there are currently no well-established treatments for OIH. Several substrates have emerged as potential modulators of OIH, including the N-methyl-D-aspartate and γ-aminobutyric acid receptors, and most notably, the innate neuroimmune system. This review summarizes the neurobiology of OIH in the context of clinical treatment; specifically, we review evidence for several pathways that show promise for the treatment of pain going forward, as prospective adjuvants to opioid analgesics. Overall, we suggest that this paradoxical state be considered an additional target of clinical treatment for chronic pain.

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Section: Neurosteroidsmentioning

confidence: 99%

Targeting Opioid-Induced Hyperalgesia in Clinical Treatment: Neurobiological Considerations

et al. 2015

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“…The CNS depressant action of steroids has been known since 1927 when it was shown that injection of a colloidal suspension of cholesterol into cats caused deep anaesthesia [125]. Subsequently, cholesterol was found to potentiate the anaesthetic actions of pentobarbitone [126], but it was not until the extensive investigations of Seyle [127] that it became apparent that a wide range of natural and synthetic steroids have anaesthetic actions.…”

Section: Steroids That Influence Gaba a Receptorsmentioning

confidence: 99%

“…As noted in section 6, cholesterol has been long known to produce deep anaesthesia in cats following injection of a colloidal suspension [125] and to potentiate pentobarbitoneinduced anaesthesia [126]. Dietary cholesterol and agents that alter cholesterol levels may influence GABA A receptor function in the brain.…”

Section: Dietary and Environmental Chemicals That May Influence Gaba mentioning

confidence: 99%

GABAA Receptor Channel Pharmacology

Johnston

2005

CPD

226

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GABA(A) receptor channels are ubiquitous in the mammalian central nervous system mediating fast inhibitory neurotransmission by becoming permeant to chloride ions in response to GABA. The emphasis of this review is on the rich chemical diversity of ligands that influence GABA(A) receptor function. Such diversity provides many avenues for the design and development of new chemical entities acting on GABA(A) receptors. There is also a significant diversity of GABA(A) receptor subtypes composed of different protein subunits. The discovery of subtype specific agents is a major challenge in the continuing development of GABA(A) receptor pharmacology. Leads for the discovery of new chemical entities that influence GABA(A) receptors come from using recombinant GABA(A) receptors of known subunit composition as has been elegantly demonstrated by the refining of benzodiazepine actions with alpha1 subunit preferring agents showing sedative properties but not anxiolytic properties. The most recent advances in the therapeutic use of agents acting on GABA(A) receptors concern the promotion of sound sleep. Many herbal medicines are used to promote sleep and many of their active ingredients include flavonoids and terpenoids known to modulate GABA(A) receptor function.

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“…Les connaissances actuelles sur les effets membranaires rapides des neurostéroïdes sont la conséquence directe des travaux précurseurs de Cashin et Moravek [17] et de Selye [87] qui démontrèrent successivement les propriétés anesthésiques du cholestérol et de certaines hormones naturelles lorsqu'elles sont injectées chez l'animal. De façon intéressante, les anesthési-ques stéroïdiens comme l'alfaxalone (3α-hydroxy-5α-pregnane-11,20-dione) ont une structure chimique très semblable aux neurostéroïdes réduits en positions 3α (Fig.…”

Section: Effets Membranaires Des (Neuro)stéroïdesunclassified

Neurosteroid and pain

Keller

Poisbeau

2009

Douleur analg

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Les neurostéroïdes sont synthétisés par les cellules du système nerveux à partir de cholestérol ou de précurseurs stéroïdiens circulants. Comme les autres stéroïdes, ils exercent de puissants effets activationnels sur les fonctions cérébrales dont une partie est médiée par l'action sur des récepteurs membranaires. Cette revue fait le point sur les effets membranaires rapides des neurostéroïdes et leurs conséquences fonctionnelles sur l'expression douloureuse en expérimentation animale. À côté de leurs effets thérapeutiques potentiels en application exogène, les neurostéroïdes endogènes sont impliqués dans la modulation des messages « douloureux » périphériques dans la grande majorité des structures relais du système nociceptif en situations physiologique ou pathologique. La meilleure connaissance des mécanismes qui contrôlent la neurosté-roïdogenèse endogène devrait permettre à l'avenir d'ouvrir de nouvelles pistes thérapeutiques pour le traitement des douleurs neuropathiques et des douleurs inflammatoires. Mots clés Nociception · Récepteur mitochondrial des benzodiazépines · Douleurs inflammatoire ou neuropathique · Récepteurs GABA A · AlloprégnanoloneAbstract Neurosteroids are synthesized by nerve cells from cholesterol or from circulating steroid precursors. Like other steroids, they exert powerful activational effects on brain functions, part of which are mediated by neurotransmitter receptor expressed at the plasma membrane. This review provides an update on the membrane effects of neurosteroids and their functional consequences on the expression in pain symptoms in animal experimentation. Apart from their potential therapeutic use if exogenously administered, endogenous neurosteroids are involved in the modulation peripheral "pain" messages in the vast majority of relay nociceptive structures, in physiological and pathological states. A better understanding of the mechanisms that control neurosteroidogenesis is expected to open new therapeutic strategies for the treatment of neuropathic and inflammatory pain.

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The Physiological Action of Cholesterol

Cited by 48 publications

References 0 publications

Targeting Opioid-Induced Hyperalgesia in Clinical Treatment: Neurobiological Considerations

Targeting Opioid-Induced Hyperalgesia in Clinical Treatment: Neurobiological Considerations

GABAA Receptor Channel Pharmacology

Neurosteroid and pain

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