Activation of the spinal cord complement cascade might contribute to mechanical allodynia induced by three animal models of spinal sensitization.
The present series of experiments examined whether the complement cascade might play a key role in the expression of mechanical allodynia. Soluble complement receptor 1 (sCR1) was used to block the activation of the membrane attack pathway of the complement cascade. In doing so, sCR1 prevents the formation of the biologically active end products C3a, C5a, and membrane attack complexes (MACs). Intrathecal sCR1 had no effect on the behavioral responses of control groups. In contrast, blockade of this pathway abolished the expression of mechanical allodynia induced by peripheral nerve inflammation (sciatic inflammatory neuropathy model), partial sciatic nerve injury (chronic constriction injury model), and intrathecal injection of human immunodeficiency virus type 1 gp120, a viral envelope protein that activates glia. The fact that enhanced nociception was prevented or reversed in all 3 paradigms suggests that complement might be broadly involved in spinally mediated pain enhancement. The mechanisms whereby complement activation might potentially affect the functioning of microglia, astrocytes, and neurons are discussed. The complement cascade has not been previously implicated in spinal sensitization. These data suggest that complement activation within the spinal cord might contribute to enhanced pain states and provide additional evidence for immune regulation of pain transmission.
Twining
Carin M
CM
Department of Psychology and the Center of Neuroscience, University of Colorado at Boulder, 80309, USA.
Sloane
Evan M
EM
Schoeniger
Diana K
DK
Milligan
Erin D
ED
Martin
David
D
Marsh
Henry
H
Maier
Steven F
SF
Watkins
Linda R
LR
D000818:Animals; D002908:Chronic Disease; D015926:Complement C3a / Q000276:immunology; D015936:Complement C5a / Q000276:immunology; D003165:Complement System Proteins / Q000276:immunology*; D004195:Disease Models, Animal; D015699:HIV Envelope Protein gp120 / Q000494:pharmacology; D007278:Injections, Spinal; D008297:Male; D009619:Nociceptors / Q000276:immunology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011951:Receptors, Complement; D011994:Recombinant Proteins / Q000494:pharmacology; D020426:Sciatic Neuropathy / Q000188:drug therapy / Q000276:immunology* / Q000503:physiopathology*; D013116:Spinal Cord / Q000276:immunology / Q000503:physiopathology*
D015699:HIV Envelope Protein gp120; D011951:Receptors, Complement; D011994:Recombinant Proteins; C082885:soluble complement inhibitor 1; D015926:Complement C3a; D015936:Complement C5a; D003165:Complement System Proteins