title: Remodelling of spinal nociceptive mechanisms in an animal model of monoarthritis.
abstract: Intra-articularly injected complete Freund's adjuvant creates in rats a chronic monoarthritis suitable for studying neuronal plasticity and chronic pain. Using such a model, we report electrophysiological and morphological evidence of alterations in somatosensory synaptic function. In arthritic rats, the baseline activity of dorsal spinal cord wide dynamic range or nociceptive-specific neurons was greater than in control animals. Moreover, neuronal responses elicited by an innocuous stimulation with von Frey filaments applied to the arthritic joint were greater in amplitude and produced the afterdischarge that normally characterizes a nociceptive response. In contrast to the response in control animals, passive movement of the arthritic joint produced an increase in the amplitude of the response of these neurons to iontophoretic application of glutamate receptor agonists over a time frame of 10-30 min. This potentiation was blocked by pretreatment with a neurokinin-1 (NK-1) receptor antagonist, suggesting the involvement of substance P. Ultrastructural analysis of the dorsal horn revealed that movement of the arthritic joint also induced NK-1 receptor internalization, indicative of nociception. Morphological examination revealed significantly increased expression of substance P and its receptor within the superficial dorsal horn of monoarthritic animals. These unique functional and chemical changes reflect alterations in both presynaptic and postsynaptic mechanisms in nociceptive transmission at the spinal level. Thus, although treatment of arthritis should obviously target its peripheral aetiology, targeting its central components is a logical therapeutic complementary objective.
authors.affiliation: Department of Physiology, McGill University, Montreal, QC, H3A 1A1, Canada.
authors.forename: Reza
authors.initials: R
authors.lastname: Sharif Naeini
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Cahill
authors.forename: Alfredo
authors.initials: A
authors.lastname: Ribeiro-da-Silva
authors.forename: Henri A
authors.initials: HA
authors.lastname: Ménard
authors.forename: James L
authors.initials: JL
authors.lastname: Henry
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D000818:Animals; D000842:Ankle / Q000473:pathology; D001168:Arthritis / Q000139:chemically induced / Q000150:complications* / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation / Q000379:methods; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005620:Freund's Adjuvant; D007839:Functional Laterality; D007150:Immunohistochemistry / Q000379:methods; D007478:Iontophoresis / Q000379:methods; D008297:Male; D016253:Microscopy, Immunoelectron; D016202:N-Methylaspartate / Q000494:pharmacology; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D009474:Neurons / Q000145:classification / Q000502:physiology* / Q000648:ultrastructure; D010146:Pain / Q000209:etiology* / Q000473:pathology; D010147:Pain Measurement / Q000379:methods; D017288:Pain Threshold / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018040:Receptors, Neurokinin-1 / Q000378:metabolism; D013116:Spinal Cord / Q000473:pathology*; D013373:Substance P / Q000378:metabolism; D013997:Time Factors; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
chemical_list: D018690:Excitatory Amino Acid Agonists; D018040:Receptors, Neurokinin-1; D013373:Substance P; D016202:N-Methylaspartate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D005620:Freund's Adjuvant