The Major Brain Endocannabinoid 2-AG Controls Neuropathic Pain and Mechanical Hyperalgesia in Patients with Neuromyelitis Optica
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{"title"=>"The Major Brain Endocannabinoid 2-AG Controls Neuropathic Pain and Mechanical Hyperalgesia in Patients with Neuromyelitis Optica", "type"=>"journal", "authors"=>[{"first_name"=>"Hannah L.", "last_name"=>"Pellkofer", "scopus_author_id"=>"13205463900"}, {"first_name"=>"Joachim", "last_name"=>"Havla", "scopus_author_id"=>"25824253800"}, {"first_name"=>"Daniela", "last_name"=>"Hauer", "scopus_author_id"=>"23989193000"}, {"first_name"=>"Gustav", "last_name"=>"Schelling", "scopus_author_id"=>"7005545976"}, {"first_name"=>"Shahnaz C.", "last_name"=>"Azad", "scopus_author_id"=>"7004888293"}, {"first_name"=>"Tania", "last_name"=>"Kuempfel", "scopus_author_id"=>"29067903800"}, {"first_name"=>"Walter", "last_name"=>"Magerl", "scopus_author_id"=>"6603733721"}, {"first_name"=>"Volker", "last_name"=>"Huge", "scopus_author_id"=>"15065212900"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "scopus"=>"2-s2.0-84881248473", "sgr"=>"84881248473", "pui"=>"369514800", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "pmid"=>"23951176", "doi"=>"10.1371/journal.pone.0071500"}, "id"=>"b768e88a-9fad-328d-bcbb-02c23851ab7a", "abstract"=>"Recurrent myelitis is one of the predominant characteristics in patients with neuromyelitis optica (NMO). While paresis, visual loss, sensory deficits, and bladder dysfunction are well known symptoms in NMO patients, pain has been recognized only recently as another key symptom of the disease. Although spinal cord inflammation is a defining aspect of neuromyelitis, there is an almost complete lack of data on altered somatosensory function, including pain. Therefore, eleven consecutive patients with NMO were investigated regarding the presence and clinical characteristics of pain. All patients were examined clinically as well as by Quantitative Sensory Testing (QST) following the protocol of the German Research Network on Neuropathic Pain (DFNS). Additionally, plasma endocannabinoid levels and signs of chronic stress and depression were determined. Almost all patients (10/11) suffered from NMO-associated neuropathic pain for the last three months, and 8 out of 11 patients indicated relevant pain at the time of examination. Symptoms of neuropathic pain were reported in the vast majority of patients with NMO. Psychological testing revealed signs of marked depression. Compared to age and gender-matched healthy controls, QST revealed pronounced mechanical and thermal sensory loss, strongly correlated to ongoing pain suggesting the presence of deafferentation-induced neuropathic pain. Thermal hyperalgesia correlated to MRI-verified signs of spinal cord lesion. Heat hyperalgesia was highly correlated to the time since last relapse of NMO. Patients with NMO exhibited significant mechanical and thermal dysesthesia, namely dynamic mechanical allodynia and paradoxical heat sensation. Moreover, they presented frequently with either abnormal mechanical hypoalgesia or hyperalgesia, which depended significantly on plasma levels of the endogenous cannabinoid 2-arachidonoylglycerole (2-AG). These data emphasize the high prevalence of neuropathic pain and hyperalgesia in patients with NMO. The degree of mechanical hyperalgesia reflecting central sensitization of nociceptive pathways seems to be controlled by the major brain endocannabinoid 2-AG.", "link"=>"http://www.mendeley.com/research/major-brain-endocannabinoid-2ag-controls-neuropathic-pain-mechanical-hyperalgesia-patients-neuromyel", "reader_count"=>44, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>4, "Student > Doctoral Student"=>3, "Researcher"=>6, "Student > Ph. D. Student"=>8, "Student > Postgraduate"=>4, "Student > Master"=>8, "Other"=>3, "Student > Bachelor"=>3, "Lecturer"=>1, "Lecturer > Senior Lecturer"=>1, "Professor"=>3}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>4, "Student > Doctoral Student"=>3, "Researcher"=>6, "Student > Ph. D. Student"=>8, "Student > Postgraduate"=>4, "Student > Master"=>8, "Other"=>3, "Student > Bachelor"=>3, "Lecturer"=>1, "Lecturer > Senior Lecturer"=>1, "Professor"=>3}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Environmental Science"=>1, "Biochemistry, Genetics and Molecular Biology"=>1, "Mathematics"=>1, "Agricultural and Biological Sciences"=>10, "Medicine and Dentistry"=>18, "Neuroscience"=>6, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Psychology"=>2, "Social Sciences"=>2}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>18}, "Neuroscience"=>{"Neuroscience"=>6}, "Social Sciences"=>{"Social Sciences"=>2}, "Psychology"=>{"Psychology"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>10}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}, "Mathematics"=>{"Mathematics"=>1}, "Unspecified"=>{"Unspecified"=>2}, "Environmental Science"=>{"Environmental Science"=>1}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}}, "reader_count_by_country"=>{"United States"=>1, "United Kingdom"=>1, "Germany"=>1, "Spain"=>1}, "group_count"=>3}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1148368"], "description"=>"<p><b>P</b>attern of abnormal somatosensory findings in patients with NMO encompassing sensory gains (black bars) and sensory losses (grey bars). Highly significant loss of sensitivity was prevalent for all non-nociceptive detection (except for tactile detection MDT, which exhibited also a similar number of abnormal gains in sensitivity). Highly significant gain of sensitivity was prevalent for all pain thresholds (except for cold pain threshold CPT) and for the painful dysesthesias elicited by non-noxious stroking tactile stimuli (dynamic mechanical allodynia DMA) and heat pain sensation elicited by non-noxious cold stimuli during the TSL procedure (paradoxical heat sensation PHS). Healthy controls did not exhibit abnormal frequencies in any of the 13 QST parameters. *p<0.05, **p<0.01, ***p<0.001, Yates-corrected Chi<sup>2</sup>-test.</p>", "links"=>[], "tags"=>["neuroscience", "Cognitive neuroscience", "pain", "Neurochemistry", "Neurochemicals", "endocannabinoids", "anesthesiology", "Pain management", "Diagnostic medicine", "Clinical neurophysiology", "Drugs and devices", "Neuropharmacology", "neurology", "Demyelinating disorders", "Neurodegenerative diseases", "Spinal cord diseases", "somatosensory", "findings"], "article_id"=>768525, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Hannah L. Pellkofer", "Joachim Havla", "Daniela Hauer", "Gustav Schelling", "Shahnaz C. Azad", "Tania Kuempfel", "Walter Magerl", "Volker Huge"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0071500.g003", "stats"=>{"downloads"=>0, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Abnormal_somatosensory_findings_in_NMO_/768525", "title"=>"Abnormal somatosensory findings in NMO.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-08-09 01:33:07"}
  • {"files"=>["https://ndownloader.figshare.com/files/1148381"], "description"=>"<p>Patient characteristics.</p>", "links"=>[], "tags"=>["neuroscience", "Cognitive neuroscience", "pain", "Neurochemistry", "Neurochemicals", "endocannabinoids", "anesthesiology", "Pain management", "Diagnostic medicine", "Clinical neurophysiology", "Drugs and devices", "Neuropharmacology", "neurology", "Demyelinating disorders", "Neurodegenerative diseases", "Spinal cord diseases"], "article_id"=>768538, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Hannah L. Pellkofer", "Joachim Havla", "Daniela Hauer", "Gustav Schelling", "Shahnaz C. Azad", "Tania Kuempfel", "Walter Magerl", "Volker Huge"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0071500.t001", "stats"=>{"downloads"=>1, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Patient_characteristics_/768538", "title"=>"Patient characteristics.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-08-09 01:33:07"}
  • {"files"=>["https://ndownloader.figshare.com/files/1148363"], "description"=>"<p>A: The sensory profile by comprehensive quantitative sensory testing (QST) shows significant sensory loss (negative z-values) for thermal detection (CDT, WDT, TSL) and vibration detection (VDT) in both extremities, significant sensory gain (positive z-values) for noxious heat (HPT) in the hand dorsum. B: Patients with NMO experienced pronounced dysesthesia to non-noxious mechanical and thermal stimulation in both extremities, namely pain to stroking with non-noxious light tactile stimuli (dynamic mechanical allodynia DMA) and paradoxical heat sensation (PHS) to stimulation with non-noxious cold stimuli during the TSL procedure (alternating cold and warm stimuli). *p<0.05, **p<0.01, ***p<0.001, t-test.</p>", "links"=>[], "tags"=>["neuroscience", "Cognitive neuroscience", "pain", "Neurochemistry", "Neurochemicals", "endocannabinoids", "anesthesiology", "Pain management", "Diagnostic medicine", "Clinical neurophysiology", "Drugs and devices", "Neuropharmacology", "neurology", "Demyelinating disorders", "Neurodegenerative diseases", "Spinal cord diseases", "sensory", "patients", "nmo", "deviation"], "article_id"=>768520, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Hannah L. Pellkofer", "Joachim Havla", "Daniela Hauer", "Gustav Schelling", "Shahnaz C. Azad", "Tania Kuempfel", "Walter Magerl", "Volker Huge"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0071500.g001", "stats"=>{"downloads"=>0, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Pattern_of_sensory_changes_in_patients_with_NMO_normalized_to_mean_and_standard_deviation_of_healthy_control_group_/768520", "title"=>"Pattern of sensory changes in patients with NMO (normalized to mean and standard deviation of healthy control group).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-08-09 01:33:07"}
  • {"files"=>["https://ndownloader.figshare.com/files/1148372"], "description"=>"<p>Mean plasma levels of the endogenous cannabinoid lipids 2-arachidonoylglycerol (2-AG) and N-arachidonoylethanolamide (AEA, anandamide) were increased in patients with NMO compared to age matched healthy controls. (*)p<0.10, **p<0.01.</p>", "links"=>[], "tags"=>["neuroscience", "Cognitive neuroscience", "pain", "Neurochemistry", "Neurochemicals", "endocannabinoids", "anesthesiology", "Pain management", "Diagnostic medicine", "Clinical neurophysiology", "Drugs and devices", "Neuropharmacology", "neurology", "Demyelinating disorders", "Neurodegenerative diseases", "Spinal cord diseases", "plasma"], "article_id"=>768529, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Hannah L. Pellkofer", "Joachim Havla", "Daniela Hauer", "Gustav Schelling", "Shahnaz C. Azad", "Tania Kuempfel", "Walter Magerl", "Volker Huge"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0071500.g004", "stats"=>{"downloads"=>0, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Endocannabinoid_plasma_levels_in_NMO_/768529", "title"=>"Endocannabinoid plasma levels in NMO.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-08-09 01:33:07"}
  • {"files"=>["https://ndownloader.figshare.com/files/1148366"], "description"=>"<p>A: Heat pain thresholds in patients with NMO (NMO) compared to healthy controls (HC) differed significantly in the hands, but not feet. <b>B</b>: Patients with NMO (NMO) in patients with an acute MRI-verified cervical lesion (NMO w) were significantly more heat pain-sensitive in both extremities and also tended to be more cold pain-sensitive than patients without (NMO w/o). For both thermal pain modalities the hyperalgesia tended to be more pronounced in the hands than feet. <b>C</b>: Collapsing data from both extremities revealed that patients with an acute MRI-verified cervical lesion (NMO w) were significantly more cold pain-sensitive than patients without (NMO w/o). <b>D</b>: Correlations of heat pain thresholds to the time span since the last relapse of an acute NMO attack was high in the hand (closed circles; r = 0.77) and feet (open circles; r = 0.68). This correlation also persisted at the same level, when normalized for gender and age. The correlations indicated that NMO relapses may have induced a severe heat hyperalgesia that subsided slowly during the course of remission. <sup>(</sup>*<sup>)</sup>p<0.10, *p<0.05, **p<0.01, ***p<0.001, t-test.</p>", "links"=>[], "tags"=>["neuroscience", "Cognitive neuroscience", "pain", "Neurochemistry", "Neurochemicals", "endocannabinoids", "anesthesiology", "Pain management", "Diagnostic medicine", "Clinical neurophysiology", "Drugs and devices", "Neuropharmacology", "neurology", "Demyelinating disorders", "Neurodegenerative diseases", "Spinal cord diseases", "thresholds"], "article_id"=>768523, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Hannah L. Pellkofer", "Joachim Havla", "Daniela Hauer", "Gustav Schelling", "Shahnaz C. Azad", "Tania Kuempfel", "Walter Magerl", "Volker Huge"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0071500.g002", "stats"=>{"downloads"=>0, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Thermal_thresholds_in_NMO_/768523", "title"=>"Thermal thresholds in NMO.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-08-09 01:33:07"}
  • {"files"=>["https://ndownloader.figshare.com/files/1148380"], "description"=>"<p>Clinical characteristics of neuropathic pain.</p>", "links"=>[], "tags"=>["neuroscience", "Cognitive neuroscience", "pain", "Neurochemistry", "Neurochemicals", "endocannabinoids", "anesthesiology", "Pain management", "Diagnostic medicine", "Clinical neurophysiology", "Drugs and devices", "Neuropharmacology", "neurology", "Demyelinating disorders", "Neurodegenerative diseases", "Spinal cord diseases", "neuropathic"], "article_id"=>768537, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Hannah L. Pellkofer", "Joachim Havla", "Daniela Hauer", "Gustav Schelling", "Shahnaz C. Azad", "Tania Kuempfel", "Walter Magerl", "Volker Huge"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0071500.t002", "stats"=>{"downloads"=>2, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Clinical_characteristics_of_neuropathic_pain_/768537", "title"=>"Clinical characteristics of neuropathic pain.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-08-09 01:33:07"}
  • {"files"=>["https://ndownloader.figshare.com/files/1148378"], "description"=>"a<p>QST-parameter; expressed as arithmetic mean ± SEM or as geometric mean (log<sub>10</sub>mean ± SEM; geometric mean retransformed from log<sub>10</sub>mean.</p>b<p>Thermal detection thresholds are expressed as the difference from baseline temperature (BL = 32°C).</p>c<p>Yates corrected Chi-square.</p>", "links"=>[], "tags"=>["neuroscience", "Cognitive neuroscience", "pain", "Neurochemistry", "Neurochemicals", "endocannabinoids", "anesthesiology", "Pain management", "Diagnostic medicine", "Clinical neurophysiology", "Drugs and devices", "Neuropharmacology", "neurology", "Demyelinating disorders", "Neurodegenerative diseases", "Spinal cord diseases", "sensory", "patients", "neuromyelitis", "optica", "matched", "controls"], "article_id"=>768535, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Hannah L. Pellkofer", "Joachim Havla", "Daniela Hauer", "Gustav Schelling", "Shahnaz C. Azad", "Tania Kuempfel", "Walter Magerl", "Volker Huge"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0071500.t004", "stats"=>{"downloads"=>4, "page_views"=>18, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Quantitative_sensory_testing_QST_in_patients_with_neuromyelitis_optica_NMO_vs_matched_healthy_controls_HC_/768535", "title"=>"Quantitative sensory testing (QST) in patients with neuromyelitis optica (NMO) vs. matched healthy controls (HC).", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-08-09 01:33:07"}
  • {"files"=>["https://ndownloader.figshare.com/files/1148379"], "description"=>"<p>The scales of the SF-36 score from 0–100, with 0 indicating worst health and 100 the best.</p><p>PF: Physical Functioning, RP: Role Limitations, Physical:, BP: Bodily Pain, GH: General Health, VT: Vitality, SF: Social Functioning, RE: Role Limitations, Emotional, MH: Emotional Well-Being, PCS: Physical Component Summary Score MCS: Mental Component Summary Score.</p><p>n.s.: not significant.</p><p>Z-Score: SF-36 data were normalized to a US-General population (n = 2393).</p>", "links"=>[], "tags"=>["neuroscience", "Cognitive neuroscience", "pain", "Neurochemistry", "Neurochemicals", "endocannabinoids", "anesthesiology", "Pain management", "Diagnostic medicine", "Clinical neurophysiology", "Drugs and devices", "Neuropharmacology", "neurology", "Demyelinating disorders", "Neurodegenerative diseases", "Spinal cord diseases"], "article_id"=>768536, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Hannah L. Pellkofer", "Joachim Havla", "Daniela Hauer", "Gustav Schelling", "Shahnaz C. Azad", "Tania Kuempfel", "Walter Magerl", "Volker Huge"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0071500.t003", "stats"=>{"downloads"=>6, "page_views"=>30, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Health_related_Quality_of_Life_SF_36_/768536", "title"=>"Health related Quality of Life: (SF-36).", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-08-09 01:33:07"}
  • {"files"=>["https://ndownloader.figshare.com/files/1148377"], "description"=>"<p>The figure displays correlations of quantitative sensory testing of pain sensitivity (normalized pain thresholds) to plasma concentrations of the cannabinoid lipids <i>N</i>-arachidonoylethanolamide (AEA, anandamide) and 2-arachidonoylglycerol (2-AG) in patients with NMO. Therefore, the results of all QST parameters testing mechanical (PPT, MPT) or thermal (CPT, HPT) pain sensitivity in each patient and each test site (both hands and feet) were analysed. <b>A</b>: The plasma concentration of AEA was weakly positively correlated to normalized pain thresholds collapsing estimates in the hand and feet dorsums. <b>B</b>: The plasma concentration of 2-AG was significantly negatively correlated to normalized pain thresholds. <b>C</b>: Correlation of 2-AG concentrations to normalized pain thresholds in hand and feet dorsums differed significantly between thermal (no correlation) and mechanical pain thresholds (substantial negative correlation). The latter varied by more than four standard deviations between the lowest and highest concentration of plasma 2-AG in an NMO patient. Thermal pain thresholds (open symbols), mechanical pain thresholds (closed symbols).</p>", "links"=>[], "tags"=>["neuroscience", "Cognitive neuroscience", "pain", "Neurochemistry", "Neurochemicals", "endocannabinoids", "anesthesiology", "Pain management", "Diagnostic medicine", "Clinical neurophysiology", "Drugs and devices", "Neuropharmacology", "neurology", "Demyelinating disorders", "Neurodegenerative diseases", "Spinal cord diseases", "endocannabinoid", "plasma"], "article_id"=>768534, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Hannah L. Pellkofer", "Joachim Havla", "Daniela Hauer", "Gustav Schelling", "Shahnaz C. Azad", "Tania Kuempfel", "Walter Magerl", "Volker Huge"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0071500.g005", "stats"=>{"downloads"=>0, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Correlations_between_pain_sensitivity_and_endocannabinoid_plasma_levels_/768534", "title"=>"Correlations between pain sensitivity and endocannabinoid plasma levels.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-08-09 01:33:07"}

PMC Usage Stats | Further Information

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Relative Metric

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