Decreased Brain Neurokinin-1 Receptor Availability in Chronic Tennis Elbow

Substance P is released in painful and inflammatory conditions, affecting both peripheral processes and the central nervous system neurokinin 1 (NK1) receptor. There is a paucity of data on human brain alterations in NK1 expression, how this system may be affected by treatment, and interactions betw...

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Published inPloS one Vol. 11; no. 9; p. e0161563
Main Authors Linnman, Clas, Catana, Ciprian, Svärdsudd, Kurt, Appel, Lieuwe, Engler, Henry, Långström, Bengt, Sörensen, Jens, Furmark, Tomas, Fredrikson, Mats, Borsook, David, Peterson, Magnus
Format Journal Article
LanguageEnglish
Published United States Public Library of Science 22.09.2016
Public Library of Science (PLoS)
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Online AccessGet full text
ISSN1932-6203
1932-6203
DOI10.1371/journal.pone.0161563

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Abstract Substance P is released in painful and inflammatory conditions, affecting both peripheral processes and the central nervous system neurokinin 1 (NK1) receptor. There is a paucity of data on human brain alterations in NK1 expression, how this system may be affected by treatment, and interactions between central and peripheral tissue alterations. Ten subjects with chronic tennis elbow (lateral epicondylosis) were selected out of a larger (n = 120) randomized controlled trial evaluating graded exercise as a treatment for chronic tennis elbow (lateral epicondylosis). These ten subjects were examined by positron emission tomography (PET) with the NK1-specific radioligand 11C-GR205171 before, and eight patients were followed up after treatment with graded exercise. Brain binding in the ten patients before treatment, reflecting NK1-receptor availability (NK1-RA), was compared to that of 18 healthy subjects and, longitudinally, to the eight of the original ten patients that agreed to a second PET examination after treatment. Before treatment, patients had significantly lower NK1-RA in the insula, vmPFC, postcentral gyrus, anterior cingulate, caudate, putamen, amygdala and the midbrain but not the thalamus and cerebellum, with the largest difference in the insula contralateral to the injured elbow. No significant correlations between brain NK1-RA and pain, functional severity, or peripheral NK1-RA in the affected limb were observed. In the eight patients examined after treatment, pain ratings decreased in everyone, but there were no significant changes in NK1-RA. These findings indicate a role for the substance P (SP) / NK1 receptor system in musculoskeletal pain and tissue healing. As neither clinical parameters nor successful treatment response was reflected in brain NK1-RA after treatment, this may reflect the diverse function of the SP/NK1 system in CNS and peripheral tissue, or a change too small or slow to capture over the three-month treatment.
AbstractList Substance P is released in painful and inflammatory conditions, affecting both peripheral processes and the central nervous system neurokinin 1 (NK1) receptor. There is a paucity of data on human brain alterations in NK1 expression, how this system may be affected by treatment, and interactions between central and peripheral tissue alterations. Ten subjects with chronic tennis elbow (lateral epicondylosis) were selected out of a larger (n = 120) randomized controlled trial evaluating graded exercise as a treatment for chronic tennis elbow (lateral epicondylosis). These ten subjects were examined by positron emission tomography (PET) with the NK1-specific radioligand 11C-GR205171 before, and eight patients were followed up after treatment with graded exercise. Brain binding in the ten patients before treatment, reflecting NK1-receptor availability (NK1-RA), was compared to that of 18 healthy subjects and, longitudinally, to the eight of the original ten patients that agreed to a second PET examination after treatment. Before treatment, patients had significantly lower NK1-RA in the insula, vmPFC, postcentral gyrus, anterior cingulate, caudate, putamen, amygdala and the midbrain but not the thalamus and cerebellum, with the largest difference in the insula contralateral to the injured elbow. No significant correlations between brain NK1-RA and pain, functional severity, or peripheral NK1-RA in the affected limb were observed. In the eight patients examined after treatment, pain ratings decreased in everyone, but there were no significant changes in NK1-RA. These findings indicate a role for the substance P (SP) / NK1 receptor system in musculoskeletal pain and tissue healing. As neither clinical parameters nor successful treatment response was reflected in brain NK1-RA after treatment, this may reflect the diverse function of the SP/NK1 system in CNS and peripheral tissue, or a change too small or slow to capture over the three-month treatment.
Audience Academic
Author Appel, Lieuwe
Långström, Bengt
Borsook, David
Svärdsudd, Kurt
Peterson, Magnus
Engler, Henry
Catana, Ciprian
Sörensen, Jens
Fredrikson, Mats
Linnman, Clas
Furmark, Tomas
AuthorAffiliation 3 Department of Public Health and Caring Sciences, Family Medicine and Clinical Epidemiology, Uppsala University, Uppsala, Sweden
6 Department of Biochemistry and Organic Chemistry, Uppsala University, Uppsala, Sweden
8 Department of Psychology, Uppsala University, Uppsala, Sweden
7 Neuropsychopharmacology Section, Faculty of Medicine, Imperial College, London, United Kingdom
1 Center for Pain and the Brain, Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children’s Hospital, Harvard Medical School, Boston, MA, United States of America
4 Uppsala PET Centre, Department of Radiology, Oncology and Radiation Sciences, Uppsala University, Uppsala, Sweden
5 Uruguayan Centre of Molecular Imaging (CUDIM), Faculty of Medicine and Faculty of Sciences, University of the Republic, Montevideo, Uruguay
9 Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden
Charite Universitatsmedizin Berlin, GERMANY
2 Martinos Center for Biomedical Imaging, Massachusetts General
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CitedBy_id crossref_primary_10_3389_fnins_2021_684926
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2016 Linnman et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.
2016 Linnman et al 2016 Linnman et al
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– notice: 2016 Linnman et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.
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Competing Interests: The authors have declared that no competing interests exist.
Conceived and designed the experiments: CL KS MP.Performed the experiments: CL KS MP LA HE BL JS MF TF.Analyzed the data: CL MP CC DB MF TF LA BL.Wrote the paper: CL MP MF TF CC DB LA.
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SubjectTerms Amygdala
Anesthesiology
Biology and Life Sciences
Brain
Brain-derived neurotrophic factor
Care and treatment
Central nervous system
Cerebellum
Clinical trials
Elbow
Elbow (anatomy)
Epidemiology
Gene expression
Hospitals
Hostages
Inflammation
Injuries
Medicine
Medicine and Health Sciences
Mesencephalon
Neurokinin NK1 receptors
Neurosciences
Oncology
Pain
Pain management
Patients
Positron emission
Positron emission tomography
Postcentral gyrus
Public health
Putamen
Research and Analysis Methods
Rodents
Social Sciences
Sports injuries
Substance P
Tennis
Tennis elbow
Thalamus
Tomography
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Title Decreased Brain Neurokinin-1 Receptor Availability in Chronic Tennis Elbow
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