Pain hypersensitivity in rats with experimental autoimmune neuritis, an animal model of human inflammatory demyelinating neuropathy.
Experimental autoimmune neuritis (EAN) is a T cell mediated autoimmune disease of the peripheral nervous system that serves as an animal model of the acute inflammatory demyelinating polyradiculoneuropathy in Guillain-Barre syndrome (GBS). Although pain is a common symptom of GBS occurring in 55-85% of cases, it is often overlooked and the underlying mechanisms are poorly understood. Here we examined whether animals with EAN exhibit signs of neuropathic pain including hyperalgesia and allodynia, and assessed their peripheral nerve autoimmune inflammation. We immunized Lewis rats with peripheral myelin P2 peptide (amino acids 57-81) emulsified with complete Freund's adjuvant, or with adjuvant only as control. P2-immunized rats developed mild to modest monophasic EAN with disease onset at day 8, peak at days 15-17, and full recovery by day 28 following immunization. Rats with EAN showed a significant decrease in withdrawal latency to thermal stimuli and withdrawal threshold to mechanical stimuli, in both hindpaws and forepaws, during the course of the disease. We observed a significant infiltration of T cells bearing alphabeta receptors, and a significant increase in antigen-presenting cells expressing MHC class II as well as macrophages, in EAN-affected rats. Our results demonstrate that animals with active EAN develop significant thermal hyperalgesia and mechanical allodynia, accompanied by pronounced autoimmune inflammation in peripheral nerves. These findings suggest that EAN is a useful model for the pain seen in many GBS patients, and may facilitate study of neuroimmune mechanisms underlying pain in autoimmune neuropathies.
Moalem-Taylor
Gila
G
School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia. gila@unsw.edu.au
Allbutt
Haydn N
HN
Iordanova
Mihaela D
MD
Tracey
David J
DJ
D000818:Animals; D004195:Disease Models, Animal; D020275:Guillain-Barre Syndrome / Q000150:complications / Q000276:immunology; D006930:Hyperalgesia / Q000150:complications / Q000276:immunology*; D007114:Immunization; D008297:Male; D018996:Myelin P2 Protein / Q000276:immunology*; D009444:Neuritis, Autoimmune, Experimental / Q000150:complications / Q000276:immunology*; D010146:Pain / Q000150:complications / Q000276:immunology*; D017288:Pain Threshold / Q000502:physiology; D010446:Peptide Fragments; D051381:Rats; D011917:Rats, Inbred Lew; D012584:Sciatic Nerve / Q000166:cytology / Q000276:immunology* / Q000503:physiopathology; D013601:T-Lymphocytes / Q000276:immunology
D018996:Myelin P2 Protein; D010446:Peptide Fragments