title: Decreased Brain Neurokinin-1 Receptor Availability in Chronic Tennis Elbow.
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.
authors.affiliation: 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.
authors.forename: Clas
authors.initials: C
authors.lastname: Linnman
authors.affiliation: Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States of America.
authors.forename: Ciprian
authors.initials: C
authors.lastname: Catana
authors.affiliation: Department of Public Health and Caring Sciences, Family Medicine and Clinical Epidemiology, Uppsala University, Uppsala, Sweden.
authors.forename: Kurt
authors.initials: K
authors.lastname: Svärdsudd
authors.affiliation: Uppsala PET Centre, Department of Radiology, Oncology and Radiation Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Lieuwe
authors.initials: L
authors.lastname: Appel
authors.affiliation: Uppsala PET Centre, Department of Radiology, Oncology and Radiation Sciences, Uppsala University, Uppsala, Sweden.|Uruguayan Centre of Molecular Imaging (CUDIM), Faculty of Medicine and Faculty of Sciences, University of the Republic, Montevideo, Uruguay.
authors.forename: Henry
authors.initials: H
authors.lastname: Engler
authors.affiliation: Uppsala PET Centre, Department of Radiology, Oncology and Radiation Sciences, Uppsala University, Uppsala, Sweden.|Department of Biochemistry and Organic Chemistry, Uppsala University, Uppsala, Sweden.|Neuropsychopharmacology Section, Faculty of Medicine, Imperial College, London, United Kingdom.
authors.forename: Bengt
authors.initials: B
authors.lastname: Långström
authors.affiliation: Uppsala PET Centre, Department of Radiology, Oncology and Radiation Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Jens
authors.initials: J
authors.lastname: Sörensen
authors.affiliation: Department of Psychology, Uppsala University, Uppsala, Sweden.
authors.forename: Tomas
authors.initials: T
authors.lastname: Furmark
authors.affiliation: Department of Psychology, Uppsala University, Uppsala, Sweden.|Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.
authors.forename: Mats
authors.initials: M
authors.lastname: Fredrikson
authors.affiliation: 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.
authors.forename: David
authors.initials: D
authors.lastname: Borsook
authors.affiliation: Department of Public Health and Caring Sciences, Family Medicine and Clinical Epidemiology, Uppsala University, Uppsala, Sweden.
authors.forename: Magnus
authors.initials: M
authors.lastname: Peterson