Abstract | UNLABELLED: 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. PERSPECTIVE: 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.
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Authors | Marissa de Mos, André Laferrière, Magali Millecamps, Mercedes Pilkington, Miriam C J M Sturkenboom, Frank J P M Huygen, Terence J Coderre |
Journal | The journal of pain
(J Pain)
Vol. 10
Issue 11
Pg. 1161-9
(Nov 2009)
ISSN: 1528-8447 [Electronic] United States |
PMID | 19878863
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- NF-kappa B
- Pyrrolidines
- Thiocarbamates
- pyrrolidine dithiocarbamic acid
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Topics |
- Animals
- Cell Nucleus
(metabolism)
- Cold Temperature
- Complex Regional Pain Syndromes
(drug therapy, metabolism)
- Disease Models, Animal
- Dose-Response Relationship, Drug
- Male
- Muscle, Skeletal
(metabolism)
- NF-kappa B
(antagonists & inhibitors, metabolism)
- Pain Measurement
- Physical Stimulation
- Pyrrolidines
(administration & dosage, pharmacology)
- Rats
- Rats, Long-Evans
- Reperfusion Injury
(drug therapy, metabolism)
- Spinal Cord
(metabolism)
- Thiocarbamates
(administration & dosage, pharmacology)
- Time Factors
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