BACKGROUND: Both facilitatory and inhibitory effects of the sympathetic nervous system (SNS) on experimental arthritis have been reported. It is unknown whether such bidirectional effects are inherent to all experimental arthritis models and/or whether critical time windows exist for influences of the SNS on inflammation. OBJECTIVES: To assess the effect of sympathectomy at different time points on the course and severity of murine antigen-induced arthritis (AIA). METHODS: AIA was induced in mice. Chemical sympathectomy with 6-hydroxydopamine was carried out either neonatally, in the immunisation phase, or immediately before AIA elicitation, or during the chronic phase. In sympathectomised and non-sympathectomised AIA mice the inflammatory process (joint swelling, histopathology of inflammation and joint destruction), pain-related behaviour and cellular and humoral immune responses were analysed. RESULTS: Sympathectomy during AIA induction or neonatal sympathectomy significantly reduced the severity of acute AIA. Neither sympathectomy in the immunisation phase nor in the chronic phase influenced AIA. Flare-up reactions were reduced by sympathectomy just before flare-up or during the initial acute AIA stage. Sympathectomised AIA mice showed less hyperalgesia. Sympathectomy significantly reduced interleukin (IL) 2, IL-17 and transforming growth factor β in supernatants from lymph nodes and/or spleen cells and antigen-specific Th1-associated IgG2a in serum; IgG1 titres were unaffected. The ß blocker, propranolol, and the norepinephrine reuptake inhibitor bupropion produced similar anti-inflammatory effects, whereas the ß-adrenergic agonist isoproterenol increased AIA severity in neonatally sympathectomised mice. CONCLUSIONS: Sympathetic activity mainly increases the severity of acute episodes of immune-mediated arthritis. Therapeutic reduction of sympathetic activity at acute stages attenuates inflammation, hyperalgesia and proinflammatory immune parameters.
BACKGROUND: Both facilitatory and inhibitory effects of the sympathetic nervous system (SNS) on experimental arthritis have been reported. It is unknown whether such bidirectional effects are inherent to all experimental arthritis models and/or whether critical time windows exist for influences of the SNS on inflammation. OBJECTIVES: To assess the effect of sympathectomy at different time points on the course and severity of murine antigen-induced arthritis (AIA). METHODS: AIA was induced in mice. Chemical sympathectomy with 6-hydroxydopamine was carried out either neonatally, in the immunisation phase, or immediately before AIA elicitation, or during the chronic phase. In sympathectomised and non-sympathectomised AIA mice the inflammatory process (joint swelling, histopathology of inflammation and joint destruction), pain-related behaviour and cellular and humoral immune responses were analysed. RESULTS: Sympathectomy during AIA induction or neonatal sympathectomy significantly reduced the severity of acute AIA. Neither sympathectomy in the immunisation phase nor in the chronic phase influenced AIA. Flare-up reactions were reduced by sympathectomy just before flare-up or during the initial acute AIA stage. Sympathectomised AIA mice showed less hyperalgesia. Sympathectomy significantly reduced interleukin (IL) 2, IL-17 and transforming growth factor β in supernatants from lymph nodes and/or spleen cells and antigen-specific Th1-associated IgG2a in serum; IgG1 titres were unaffected. The ß blocker, propranolol, and the norepinephrine reuptake inhibitor bupropion produced similar anti-inflammatory effects, whereas the ß-adrenergic agonist isoproterenol increased AIA severity in neonatally sympathectomised mice. CONCLUSIONS: Sympathetic activity mainly increases the severity of acute episodes of immune-mediated arthritis. Therapeutic reduction of sympathetic activity at acute stages attenuates inflammation, hyperalgesia and proinflammatory immune parameters.
Authors: H-G Schaible; H-D Chang; S Grässel; H Haibel; A Hess; T Kamradt; A Radbruch; G Schett; C Stein; R H Straub Journal: Z Rheumatol Date: 2018-05 Impact factor: 1.372
Authors: Manish K Jha; Abu Minhajuddin; Bharathi S Gadad; Tracy Greer; Bruce Grannemann; Abigail Soyombo; Taryn L Mayes; A John Rush; Madhukar H Trivedi Journal: Psychoneuroendocrinology Date: 2017-01-24 Impact factor: 4.905
Authors: Manish K Jha; Abu Minhajuddin; Bharathi S Gadad; Tracy L Greer; Taryn L Mayes; Madhukar H Trivedi Journal: Brain Behav Immun Date: 2017-07-08 Impact factor: 7.217
Authors: Christina Van; Michael C Condro; Kenny Lov; Ruoyan Zhu; Patrick T Ricaflanca; Henly H Ko; Anna L Diep; Anh Q Hoang; Joseph Pisegna; Hermann Rohrer; James A Waschek Journal: J Mol Neurosci Date: 2018-07-30 Impact factor: 3.444
Authors: Enrico Leipold; Lutz Liebmann; G Christoph Korenke; Theresa Heinrich; Sebastian Giesselmann; Jonathan Baets; Matthias Ebbinghaus; R Oliver Goral; Tommy Stödberg; J Christopher Hennings; Markus Bergmann; Janine Altmüller; Holger Thiele; Andrea Wetzel; Peter Nürnberg; Vincent Timmerman; Peter De Jonghe; Robert Blum; Hans-Georg Schaible; Joachim Weis; Stefan H Heinemann; Christian A Hübner; Ingo Kurth Journal: Nat Genet Date: 2013-09-15 Impact factor: 38.330