title: 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 investigated the effects of active immunisation with a weakly encephalitogenic epitope of MBP (MBP87-99) and its mutant APL (Cyclo-87-99[A(91),A(96)]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.
authors: School of Medical Sciences, UNSW Medicine, UNSW Australia, Sydney, NSW 2052, Australia. Electronic address: h.c.perera@student.unsw.edu.au.
authors: Chamini J
authors: CJ
authors: Perera
authors: School of Medical Sciences, UNSW Medicine, UNSW Australia, Sydney, NSW 2052, Australia. Electronic address: justin.lees@unsw.edu.au.
authors: Justin G
authors: JG
authors: Lees
authors: School of Medical Sciences, UNSW Medicine, UNSW Australia, Sydney, NSW 2052, Australia. Electronic address: s.duffy@student.unsw.edu.au.
authors: Samuel S
authors: SS
authors: Duffy
authors: School of Medical Sciences, UNSW Medicine, UNSW Australia, Sydney, NSW 2052, Australia. Electronic address: preet.singh@student.unsw.edu.au.
authors: Preet G S
authors: PG
authors: Makker
authors: School of Medical Sciences, UNSW Medicine, UNSW Australia, Sydney, NSW 2052, Australia. Electronic address: brett.fivelman@gmail.com.
authors: Brett
authors: B
authors: Fivelman
authors: Centre for Chronic Disease, College of Health and Biomedicine, Victoria University, Melbourne, VIC Australia. Electronic address: vasso@scientist.com.
authors: Vasso
authors: V
authors: Apostolopoulos
authors: School of Medical Sciences, UNSW Medicine, UNSW Australia, Sydney, NSW 2052, Australia. Electronic address: gila@unsw.edu.au.
authors: Gila
authors: G
authors: Moalem-Taylor
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000187:drug effects; D005620:Freund's Adjuvant / Q000633:toxicity; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006801:Humans; D006967:Hypersensitivity / Q000209:etiology* / Q000378:metabolism; D008024:Ligands; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D004676:Myelin Basic Protein / Q000276:immunology / Q000633:toxicity*; D009187:Myelitis / Q000139:chemically induced / Q000150:complications / Q000276:immunology; D010146:Pain / Q000139:chemically induced / Q000503:physiopathology*; D010147:Pain Measurement; D017288:Pain Threshold; D010446:Peptide Fragments / Q000276:immunology / Q000633:toxicity*; D051381:Rats; D011917:Rats, Inbred Lew; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors; D014611:Vaccination / Q000009:adverse effects
chemical_list: D000949:Histocompatibility Antigens Class II; D008024:Ligands; D004676:Myelin Basic Protein; D010446:Peptide Fragments; C107908:myelin basic protein 85-99; D005620:Freund's Adjuvant
keywords: Altered peptide ligand; Experimental autoimmune encephalomyelitis; Myelin basic protein; Neuroinflammation; Neuropathic pain; Pain hypersensitivity