Effects of active immunisation with myelin basic protein and myelin-derived altered peptide ligand on pain hypersensitivity and neuroinflammation

Abstract Neuropathic pain is a debilitating condition in multiple sclerosis and experimental autoimmune encephalomyelitis (EAE). Specific myelin basic protein (MBP) peptides are encephalitogenic, and myelin-derived altered peptide ligands (APLs) are capable of preventing and ameliorating EAE. We inv...

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Bibliographic Details
Published in:Journal of neuroimmunology 2015-09, Vol.286, p.59-70
Main Authors: Perera, Chamini J, Lees, Justin G, Duffy, Samuel S, Makker, Preet G.S, Fivelman, Brett, Apostolopoulos, Vasso, Moalem-Taylor, Gila
Format: Article
Language:English
Subjects:
Allergy and Immunology
Altered peptide ligand
Animals
Disease Models, Animal
Experimental autoimmune encephalomyelitis
Exploratory Behavior - drug effects
Freund's Adjuvant - toxicity
Histocompatibility Antigens Class II - metabolism
Humans
Hypersensitivity - etiology
Hypersensitivity - metabolism
Ligands
Lymphocyte Activation - immunology
Male
Microglia - drug effects
Microglia - metabolism
Myelin basic protein
Myelin Basic Protein - immunology
Myelin Basic Protein - toxicity
Myelitis - chemically induced
Myelitis - complications
Myelitis - immunology
Neuroinflammation
Neurology
Neuropathic pain
Pain - chemically induced
Pain - physiopathology
Pain hypersensitivity
Pain Measurement
Pain Threshold
Peptide Fragments - immunology
Peptide Fragments - toxicity
Rats
Rats, Inbred Lew
Spinal Cord - metabolism
Spinal Cord - pathology
T-Lymphocytes - drug effects
T-Lymphocytes - metabolism
Time Factors
Vaccination - adverse effects
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Summary:Abstract Neuropathic pain is a debilitating condition in multiple sclerosis and experimental autoimmune encephalomyelitis (EAE). Specific myelin basic protein (MBP) peptides are encephalitogenic, and myelin-derived altered peptide ligands (APLs) are capable of preventing and ameliorating EAE. We investigated the effects of active immunisation with a weakly encephalitogenic epitope of MBP (MBP87–99 ) and its mutant APL (Cyclo-87–99[A91 ,A96 ]MBP87–99 ) on pain hypersensitivity and neuroinflammation in Lewis rats. MBP-treated rats exhibited significant mechanical and thermal pain hypersensitivity associated with infiltration of T cells, MHC class II expression and microglia activation in the spinal cord, without developing clinical signs of paralysis. Co-immunisation with APL significantly decreased pain hypersensitivity and neuroinflammation emphasising the important role of neuroimmune crosstalk in neuropathic pain.
ISSN:0165-5728
1872-8421
DOI:10.1016/j.jneuroim.2015.07.004