Spreading depression induced by microinjection of enkephalins into the hippocampus and neocortex

Sprick, Ulrich; Oitzl, M.-S.; Ornstein, Kurt; Huston, Joseph P.

doi:10.1016/0006-8993(81)90897-0

Cited by 35 publications

(4 citation statements)

References 32 publications

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“…Although δ receptors in Dlx5/6 neurons regulate CSD, it remains unclear whether the relevant receptor populations reside within the cortex, subcortical regions, or both. Enkephalins have been found to both elicit and inhibit CSD in rats 45 , 46 . CSD was specifically monitored in sensory cortex, as this region is more susceptible to CSD induction 23 .…”

Section: Discussionmentioning

confidence: 99%

Forebrain delta opioid receptors regulate the response of delta agonist in models of migraine and opioid-induced hyperalgesia

Dripps

Bertels

Moye

et al. 2020

Sci Rep

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Delta opioid receptor (DOR) agonists have been identified as a promising novel therapy for headache disorders. DORs are broadly expressed in several peripheral and central regions important for pain processing and mood regulation; and it is unclear which receptors regulate headache associated symptoms. In a model of chronic migraine-associated pain using the human migraine trigger, nitroglycerin, we observed increased expression of DOR in cortex, hippocampus, and striatum; suggesting a role for these forebrain regions in the regulation of migraine. To test this hypothesis, we used conditional knockout mice with DORs deleted from forebrain GABAergic neurons (Dlx-DOR), and investigated the outcome of this knockout on the effectiveness of the DOR agonist SNC80 in multiple headache models. In DOR loxP controls SNC80 blocked the development of acute and chronic cephalic allodynia in the chronic nitroglycerin model, an effect that was lost in Dlx-DOR mice. In addition, the anti-allodynic effects of SNC80 were lost in a model of opioid induced hyperalgesia/medication overuse headache in Dlx-DOR conditional knockouts. In a model reflecting negative affect associated with migraine, SNC80 was only effective in loxP controls and not Dlx-DOR mice. Similarly, SNC80 was ineffective in the cortical spreading depression model of migraine aura in conditional knockout mice. Taken together, these data indicate that forebrain DORs are necessary for the action of DOR agonists in relieving headache-related symptoms and suggest that forebrain regions may play an important role in migraine modulation.

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Section: Discussionmentioning

confidence: 99%

Forebrain delta opioid receptors regulate the response of delta agonist in models of migraine and opioid-induced hyperalgesia

Dripps

Bertels

Moye

et al. 2020

Sci Rep

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“…δ-Opioid receptors are widely expressed in the cortex (Mansour et al, 1988;Pradhan and Clarke, 2005;Pradhan et al, 2011), but their cortical function is unclear. Enkephalins, endogenous agonists at the δ-opioid receptor, have been reported to have both excitatory and inhibitory effects on cortical excitability and CSD in rodents (Sprick et al, 1981;Oitzl et al, 1985). Dual effects of δ-agonists on cortical excitability could be explained by direct inhibition of the cortex versus an indirect excitation mediated by inhibition of either cortical or subcortical inhibitory neurons.…”

Section: Discussionmentioning

confidence: 99%

δ‐Opioid receptor agonists inhibit migraine‐related hyperalgesia, aversive state and cortical spreading depression in mice

Pradhan

Smith

Zyuzin³

et al. 2014

British J Pharmacology

132

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BACKGROUND AND PURPOSEMigraine is an extraordinarily common brain disorder for which treatment options continue to be limited. Agonists that activate the δ-opioid receptor may be promising for the treatment of migraine as they are highly effective for the treatment of chronic rather than acute pain, do not induce hyperalgesia, have low abuse potential and have anxiolytic and antidepressant properties. The aim of this study was to investigate the therapeutic potential of δ-opioid receptor agonists for migraine by characterizing their effects in mouse migraine models. EXPERIMENTAL APPROACHMechanical hypersensitivity was assessed in mice treated with acute and chronic doses of nitroglycerin (NTG), a known human migraine trigger. Conditioned place aversion to NTG was also measured as a model of migraine-associated negative affect. In addition, we assessed evoked cortical spreading depression (CSD), an established model of migraine aura, in a thinned skull preparation. KEY RESULTSNTG evoked acute and chronic mechanical and thermal hyperalgesia in mice, as well as conditioned place aversion. Three different δ-opioid receptor agonists, SNC80, ARM390 and JNJ20788560, significantly reduced NTG-evoked hyperalgesia. SNC80 also abolished NTG-induced conditioned place aversion, suggesting that δ-opioid receptor activation may also alleviate the negative emotional state associated with migraine. We also found that SNC80 significantly attenuated CSD, a model that is considered predictive of migraine preventive therapies. CONCLUSIONS AND IMPLICATIONSThese data show that δ-opioid receptor agonists modulate multiple basic mechanisms associated with migraine, indicating that δ-opioid receptors are a promising therapeutic target for this disorder. Abbreviations

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“…In 1986, Olesen and Jørgensen suggested spreading depression in the hippocampus as a possible pathomechanism in TGA [ 3 ]. The hippocampus is highly susceptible to spreading depression and spreading depression has been elicited in animal experiments [ 54 , 55 ] as well as in the human hippocampus in vitro [ 56 ] and in vivo [ 57 ]. Since then, shared pathophysiological mechanisms of migraine with aura and TGA have repeatedly been suggested.…”

Section: Discussionmentioning

confidence: 99%

Value of Dynamic Susceptibility Contrast Perfusion MRI in the Acute Phase of Transient Global Amnesia

et al. 2015

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PurposeTransient global amnesia (TGA) is a transitory, short-lasting neurological disorder characterized by a sudden onset of antero- and retrograde amnesia. Perfusion abnormalities in TGA have been evaluated mainly by use of positron emission tomography (PET) or single-photon emission computed tomography (SPECT). In the present study we explore the value of dynamic susceptibility contrast perfusion-weighted MRI (PWI) in TGA in the acute phase.MethodsFrom a MRI report database we identified TGA patients who underwent MRI including PWI in the acute phase and compared these to control subjects. Quantitative perfusion maps (cerebral blood flow (CBF) and volume (CBV)) were generated and analyzed by use of Signal Processing In NMR-Software (SPIN). CBF and CBV values in subcortical brain regions were assessed by use of VOI created in FIRST, a model-based segmentation tool in the Oxford Centre for Functional Magnetic Resonance Imaging of the Brain (FMRIB) Software Library (FSL).ResultsFive TGA patients were included (2 men, 3 women). On PWI, no relevant perfusion alterations were found by visual inspection in TGA patients. Group comparisons for possible differences between TGA patients and control subjects showed significant lower rCBF values bilaterally in the hippocampus, in the left thalamus and globus pallidus as well as bilaterally in the putamen and the left caudate nucleus. Correspondingly, significant lower rCBV values were observed bilaterally in the hippocampus and the putamen as well as in the left caudate nucleus. Group comparisons for possible side differences in rCBF and rCBV values in TGA patients revealed a significant lower rCBV value in the left caudate nucleus.ConclusionsMere visual inspection of PWI is not sufficient for the assessment of perfusion changes in TGA in the acute phase. Group comparisons with healthy control subjects might be useful to detect subtle perfusion changes on PWI in TGA patients. However, this should be confirmed in larger data sets and serial PWI examinations.

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Spreading depression induced by microinjection of enkephalins into the hippocampus and neocortex

Cited by 35 publications

References 32 publications

Forebrain delta opioid receptors regulate the response of delta agonist in models of migraine and opioid-induced hyperalgesia

Forebrain delta opioid receptors regulate the response of delta agonist in models of migraine and opioid-induced hyperalgesia

δ‐Opioid receptor agonists inhibit migraine‐related hyperalgesia, aversive state and cortical spreading depression in mice

Value of Dynamic Susceptibility Contrast Perfusion MRI in the Acute Phase of Transient Global Amnesia

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