title: Localized Sympathectomy Reduces Mechanical Hypersensitivity by Restoring Normal Immune Homeostasis in Rat Models of Inflammatory Pain.
abstract: Some forms of chronic pain are maintained or enhanced by activity in the sympathetic nervous system (SNS), but attempts to model this have yielded conflicting findings. The SNS has both pro- and anti-inflammatory effects on immunity, confounding the interpretation of experiments using global sympathectomy methods. We performed a "microsympathectomy" by cutting the ipsilateral gray rami where they entered the spinal nerves near the L4 and L5 DRG. This led to profound sustained reductions in pain behaviors induced by local DRG inflammation (a rat model of low back pain) and by a peripheral paw inflammation model. Effects of microsympathectomy were evident within one day, making it unlikely that blocking sympathetic sprouting in the local DRGs or hindpaw was the sole mechanism. Prior microsympathectomy greatly reduced hyperexcitability of sensory neurons induced by local DRG inflammation observed 4 d later. Microsympathectomy reduced local inflammation and macrophage density in the affected tissues (as indicated by paw swelling and histochemical staining). Cytokine profiling in locally inflamed DRG showed increases in pro-inflammatory Type 1 cytokines and decreases in the Type 2 cytokines present at baseline, changes that were mitigated by microsympathectomy. Microsympathectomy was also effective in reducing established pain behaviors in the local DRG inflammation model. We conclude that the effect of sympathetic fibers in the L4/L5 gray rami in these models is pro-inflammatory. This raises the possibility that therapeutic interventions targeting gray rami might be useful in some chronic inflammatory pain conditions.
  
  
  
  Sympathetic blockade is used for many pain conditions, but preclinical studies show both pro- and anti-nociceptive effects. The sympathetic nervous system also has both pro- and anti-inflammatory effects on immune tissues and cells. We examined effects of a very localized sympathectomy. By cutting the gray rami to the spinal nerves near the lumbar sensory ganglia, we avoided widespread sympathetic denervation. This procedure profoundly reduced mechanical pain behaviors induced by a back pain model and a model of peripheral inflammatory pain. One possible mechanism was reduction of inflammation in the sympathetically denervated regions. This raises the possibility that therapeutic interventions targeting gray rami might be useful in some inflammatory conditions.
authors.affiliation: Pain Research Center, Department of Anesthesiology, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267, and.
authors.forename: Wenrui
authors.initials: W
authors.lastname: Xie
authors.affiliation: Pain Research Center, Department of Anesthesiology, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267, and.
authors.forename: Sisi
authors.initials: S
authors.lastname: Chen
authors.affiliation: Pain Research Center, Department of Anesthesiology, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267, and.
authors.forename: Judith A
authors.identifier: 0000-0001-9363-0551
authors.initials: JA
authors.lastname: Strong
authors.affiliation: Pain Research Center, Department of Anesthesiology, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267, and.
authors.forename: Ai-Ling
authors.initials: AL
authors.lastname: Li
authors.affiliation: Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229.
authors.forename: Ian P
authors.initials: IP
authors.lastname: Lewkowich
authors.affiliation: Pain Research Center, Department of Anesthesiology, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267, and Jun-Ming.Zhang@uc.edu.
authors.forename: Jun-Ming
authors.identifier: 0000-0003-4300-2121
authors.initials: JM
authors.lastname: Zhang
mesh_terms: D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005727:Ganglia, Spinal / Q000166:cytology / Q000601:surgery; D006706:Homeostasis / Q000187:drug effects / Q000276:immunology* / Q000502:physiology; D006930:Hyperalgesia / Q000209:etiology / Q000601:surgery*; D007249:Inflammation / Q000150:complications* / Q000209:etiology; D008012:Lidocaine / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D010146:Pain / Q000209:etiology* / Q000276:immunology*; D010147:Pain Measurement; D017288:Pain Threshold; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000502:physiology; D013562:Sympathectomy; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D000779:Anesthetics, Local; D016207:Cytokines; D008012:Lidocaine; D014446:Tyrosine 3-Monooxygenase
keywords: allodynia; cytokine; inflammation; sympathetic