PMID- 16887276 OWN - NLM STAT- MEDLINE DCOM- 20070103 LR - 20220310 IS - 0306-4522 (Print) IS - 0306-4522 (Linking) VI - 142 IP - 3 DP - 2006 Oct 27 TI - Robust increase of cutaneous sensitivity, cytokine production and sympathetic sprouting in rats with localized inflammatory irritation of the spinal ganglia. PG - 809-22 AB - We investigated the role and mechanisms of inflammatory responses within the dorsal root ganglion (DRG) in the development of chemogenic pathological pain. DRG inflammation was induced by a single deposit of the immune activator zymosan in incomplete Freund's adjuvant in the epidural space near the L5 DRG via a small hole drilled through the transverse process. After a single zymosan injection, rats developed bilateral mechanical hyperalgesia and allodynia which began by day 1 after surgery, peaked at days 3-7, and lasted up to 28 days. The number of macrophages in ipsilateral and contralateral DRGs increased significantly, lasting over 14 days. Robust glial activation was observed in inflamed ganglia. Cytokine profile analysis using a multiplexing protein array system showed that, in normal DRG, all but interleukin (IL)-5, IL-10 and granulocyte-macrophage colony stimulating factor (GM-CSF) were detectable with concentrations of up to 180 pg/mg protein. Local inflammatory irritation selectively increased IL-1beta, IL-6, IL-18, monocyte chemoattractant protein-1 (MCP-1), and growth-related oncogene (GRO/KC) up to 17-fold, and decreased IL-2 and IL-12 (p70) up to threefold. Inflaming the DRG also remarkably increased the incidence of spontaneous activity of A- and C-fibers recorded in the dorsal root. Many of the spontaneously active A-fibers exhibited a short-bursting discharge pattern. Changes in cytokines and spontaneous activity correlated with the time course of pain behaviors, especially light stroke-evoked tactile allodynia. Finally, local inflammation induced extensive sprouting of sympathetic fibers, extending from vascular processes within the inflamed DRG. These results demonstrate the feasibility of inducing chronic localized inflammatory responses in the DRG in the absence of traumatic nerve damage, and highlight the possible contribution of several inflammatory cytokines/chemokines to the generation of spontaneous activity and development and persistence of chemogenic pathologic pain. FAU - Xie, W-R AU - Xie WR AD - Department of Anesthesiology, University of Cincinnati College of Medicine, 231 Albert Sabin Way, P.O. Box 670531, Cincinnati, OH 45267-0531, USA. FAU - Deng, H AU - Deng H FAU - Li, H AU - Li H FAU - Bowen, T L AU - Bowen TL FAU - Strong, J A AU - Strong JA FAU - Zhang, J-M AU - Zhang JM LA - eng GR - R01 NS039568/NS/NINDS NIH HHS/United States GR - R01 NS045594/NS/NINDS NIH HHS/United States GR - NS39568/NS/NINDS NIH HHS/United States GR - NS45594/NS/NINDS NIH HHS/United States PT - Comparative Study PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20060802 PL - United States TA - Neuroscience JT - Neuroscience JID - 7605074 RN - 0 (Cytokines) RN - 0 (Glial Fibrillary Acidic Protein) RN - 9010-72-4 (Zymosan) RN - EC 1.14.16.2 (Tyrosine 3-Monooxygenase) SB - IM MH - Action Potentials/drug effects/physiology MH - Animals MH - Cytokines/*metabolism MH - Dose-Response Relationship, Drug MH - Functional Laterality/physiology MH - Ganglia, Spinal/drug effects/pathology/*physiopathology MH - Glial Fibrillary Acidic Protein/metabolism MH - Hyperalgesia/chemically induced/*physiopathology MH - Immunohistochemistry/methods MH - Inflammation/chemically induced/*pathology MH - Male MH - Neurons/drug effects/metabolism MH - Pain Measurement/methods MH - Protein Array Analysis/methods MH - Rats MH - Rats, Sprague-Dawley MH - Reaction Time/drug effects/physiology MH - Skin/*innervation/physiopathology MH - Sympathetic Fibers, Postganglionic/drug effects/*physiopathology MH - Time Factors MH - Tyrosine 3-Monooxygenase/metabolism MH - Zymosan PMC - PMC1661830 MID - NIHMS13085 EDAT- 2006/08/05 09:00 MHDA- 2007/01/04 09:00 PMCR- 2008/01/29 CRDT- 2006/08/05 09:00 PHST- 2006/04/17 00:00 [received] PHST- 2006/06/20 00:00 [revised] PHST- 2006/06/22 00:00 [accepted] PHST- 2006/08/05 09:00 [pubmed] PHST- 2007/01/04 09:00 [medline] PHST- 2006/08/05 09:00 [entrez] PHST- 2008/01/29 00:00 [pmc-release] AID - S0306-4522(06)00876-1 [pii] AID - 10.1016/j.neuroscience.2006.06.045 [doi] PST - ppublish SO - Neuroscience. 2006 Oct 27;142(3):809-22. doi: 10.1016/j.neuroscience.2006.06.045. Epub 2006 Aug 2.