Peri-sciatic proinflammatory cytokines, reactive oxygen species, and complement induce mirror-image neuropathic pain in rats.
In inflammatory neuropathy, immune activation near intact peripheral nerves induces mechanical allodynia. The identity of the peripheral immune product(s) that lead to these changes in pain behavior is unknown. The present series of studies utilized the sciatic inflammatory neuropathy (SIN) model to examine this question. Here, inflammatory neuropathy is created by injecting an immune activator (zymosan) around one sciatic nerve via an indwelling catheter. Our prior studies demonstrated that peri-sciatic zymosan activated macrophages and neutrophils to release proinflammatory cytokines and reactive oxygen species (ROS). In addition, zymosan is a classical activator of the complement cascade. Thus the present series of experiments examined whether any of these inflammatory mediators are involved in the initial induction of SIN-induced ipsilateral or bilateral allodynias. Peri-sciatic injection of selective inhibitors/antagonists revealed that a number of immune products are early mediators of the resultant allodynias, including proinflammatory cytokines (tumor necrosis factor, interleukin-1, and interleukin-6), ROS, and complement. Thus these immune-derived substances can markedly alter sensory nerve function at mid-axon.
Department of Psychology and the Center for Neuroscience, University of Colorado at Boulder, Campus Box 345. Boulder, CO 80309-0345, USA.
Carin M
CM
Twining
Evan M
EM
Sloane
Erin D
ED
Milligan
Marucia
M
Chacur
David
D
Martin
Stephen
S
Poole
Henry
H
Marsh
Steven F
SF
Maier
Linda R
LR
Watkins
D000818:Animals; D000906:Antibodies / Q000008:administration & dosage; D001522:Behavior, Animal; D002352:Carrier Proteins / Q000627:therapeutic use; D002374:Catalase / Q000008:administration & dosage; D003165:Complement System Proteins; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D007839:Functional Laterality; D006930:Hyperalgesia / Q000139:chemically induced / Q000276:immunology; D053590:Interleukin 1 Receptor Antagonist Protein; D015850:Interleukin-6 / Q000276:immunology; D008297:Male; D009437:Neuralgia / Q000188:drug therapy / Q000209:etiology / Q000276:immunology*; D010147:Pain Measurement; D010812:Physical Stimulation; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D011951:Receptors, Complement / Q000008:administration & dosage; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use; D047888:Receptors, Tumor Necrosis Factor, Type I; D012584:Sciatic Nerve / Q000276:immunology / Q000473:pathology; D020426:Sciatic Neuropathy / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism*; D012795:Sialoglycoproteins / Q000008:administration & dosage; D013482:Superoxide Dismutase / Q000008:administration & dosage; D053319:Tumor Necrosis Factor Decoy Receptors; D015054:Zymosan / Q000633:toxicity
D000906:Antibodies; D002352:Carrier Proteins; D016207:Cytokines; D053590:Interleukin 1 Receptor Antagonist Protein; D015850:Interleukin-6; D017382:Reactive Oxygen Species; D011951:Receptors, Complement; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D012795:Sialoglycoproteins; D053319:Tumor Necrosis Factor Decoy Receptors; C069521:recombinant human tumor necrosis factor-binding protein-1; D003165:Complement System Proteins; D015054:Zymosan; D002374:Catalase; D013482:Superoxide Dismutase