Role of NFkappaB in an animal model of complex regional pain syndrome-type I (CRPS-I).
NFkappaB is involved in several pathogenic mechanisms that are believed to underlie the complex regional pain syndrome (CRPS), including ischemia, inflammation and sensitization. Chronic postischemia pain (CPIP) has been developed as an animal model that mimics the symptoms of CRPS-I. The possible involvement of NFkappaB in CRPS-I was studied using CPIP rats. Under sodium pentobarbital anesthesia, a tourniquet was placed around the rat left ankle joint, producing 3 hours of ischemia, followed by rapid reperfusion (IR injury). NFkappaB was measured in nuclear extracts of muscle and spinal cord tissue using ELISA. Moreover, the anti-allodynic (mechanical and cold) effect was tested for systemic, intrathecal, or intraplantar treatment with the NFkappaB inhibitor pyrrolidine dithiocarbamate (PDTC). At 2 and 48 hours after IR injury, NFkappaB was elevated in muscle and spinal cord of CPIP rats compared to shams. At 7 days, NFkappaB levels were normalized in muscle, but still elevated in spinal cord tissue. Systemic PDTC treatment relieved mechanical and cold allodynia in a dose-dependent manner, lasting for at least 3 hours. Intrathecal-but not intraplantar-administration also relieved mechanical allodynia. The results suggest that muscle and spinal NFkappaB plays a role in the pathogenesis of CPIP and potentially of human CRPS.


CONCLUSIONS
Using the CPIP model, we demonstrate that NFkappaB is involved in the development of allodynia after a physical injury (ischemia and reperfusion) without direct nerve trauma. Since CPIP animals exhibit many features of human CRPS-I, this observation indicates a potential role for NFkappaB in human CRPS.
de Mos
Marissa
M
Department of Medical Informatics & Epidemiology and Biostatistics, Erasmus Medical Center, Rotterdam, the Netherlands. m.vrolijk-demos@erasmusmc.nl
Laferrière
André
A
Millecamps
Magali
M
Pilkington
Mercedes
M
Sturkenboom
Miriam C J M
MC
Huygen
Frank J P M
FJ
Coderre
Terence J
TJ
D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D003080:Cold Temperature; D020918:Complex Regional Pain Syndromes / Q000188:drug therapy / Q000378:metabolism*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010147:Pain Measurement; D010812:Physical Stimulation; D011759:Pyrrolidines / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D020318:Rats, Long-Evans; D015427:Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism; D013116:Spinal Cord / Q000378:metabolism; D013859:Thiocarbamates / Q000008:administration & dosage / Q000494:pharmacology; D013997:Time Factors
D016328:NF-kappa B; D011759:Pyrrolidines; D013859:Thiocarbamates; C020972:pyrrolidine dithiocarbamic acid