Complement activation in the peripheral nervous system following the spinal nerve ligation model of neuropathic pain.
Neuroinflammatory and neuroimmune mechanisms, as exemplified by infiltrating immune cells and activation of resident endothelial/glial cells, respectively, are known to be involved in the establishment and maintenance of chronic pain. An immune system pathway that may be involved in the activation of both immune and glial cells is complement. The complement pathway is made up of a large number of distinct plasma proteins which react with one another to opsonize pathogens and induce a series of inflammatory responses to help fight infection. Cleaved products and complexes produced by complement activation are responsible for a range of effects including mediation of immune infiltration, activation of phagocytes, opsonization/lysis of pathogens and injured cells, and production of vasoactive amines such as histamine and serotonin. Gene-expression microarray-analysis performed on the rat spinal nerve ligation (SNL) model of neuropathic pain revealed that multiple complement components including the C1 inhibitor, C1q alpha, beta, and gamma, C1r, C1s, C2, C3, C4, C7, and factors B, D, H, and P, were up-regulated while DAF was down-regulated. Regulation of C3 and DAF was confirmed by real-time RT-PCR and in situ hybridization. To test the hypothesis that complement plays a role in neuropathic pain, SNL rats were treated with cobra venom factor (CVF) to deplete plasma of complement component C3. Pain behavior was significantly attenuated in SNL rats treated with CVF as was complement activity at the ipsilateral dorsal root ganglia. Our results suggest the complement pathway might be a novel target for the development of neuropathic pain therapeutics.
Levin
Margaret E
ME
Galenea, 300 Technology Square 2nd Floor, Cambridge, MA 02139, USA MaxyBio Corporation, 675 U.S. Highway One, North Brunswick, NJ 08902, USA Bristol Myers Squibb, 311 Pennington Rocky Hill, Pennington, NJ 08534, USA Program in Molecular Structure and Function, Hospital for Sick Children, MaRS East Tower, Toronto, Ont., Canada M5G 1L7 Empi, Inc., 599 Cardigan Rd, St. Paul, MN 55126, USA Chromocell Corporation, 675 U.S. Highway One, North Brunswick, NJ 0890, USA Wyeth Research, 865 Ridge Road, Monmouth Junction, NJ 08852, USA Aestus Therapeutics, Inc., 675 U.S. Highway One, No. Brunswick, NJ 0890, USA.
Jin
Jason G
JG
Ji
Rui-Ru
RR
Tong
Jeifei
J
Pomonis
James D
JD
Lavery
Daniel J
DJ
Miller
Scott W
SW
Chiang
Lillian W
LW
D000818:Animals; D003167:Complement Activation / Q000235:genetics / Q000502:physiology*; D004195:Disease Models, Animal; D008026:Ligation; D009437:Neuralgia / Q000235:genetics / Q000276:immunology* / Q000503:physiopathology*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D017933:Peripheral Nervous System / Q000276:immunology / Q000473:pathology / Q000502:physiology; D051381:Rats; D013127:Spinal Nerves / Q000276:immunology / Q000473:pathology / Q000502:physiology*