title: Development of monosodium acetate-induced osteoarthritis and inflammatory pain in ageing mice.
abstract: Most conditions associated with ageing result from an age-related loss in the function of cells and tissues that maintain body homeostasis. In osteoarthritis (OA) patients, an inadequate response to stress or joint injury can lead to tissue destruction which can result in chronic pain. Here, we evaluated the development of monoiodoacetate (MIA)-induced OA in 3-, 15- and 22-month-old mice and assessed the pain-like behaviours and the spinal microglial changes associated with MIA administration. We observed that in aged mice, nocifensive behaviour was significantly attenuated in comparison to young adults despite similar knee joint pathology. Specifically referred mechanical allodynia associated with the MIA initial inflammatory phase (0-10 days) was significantly attenuated in 22-month-old mice. In contrast, the late phase of MIA-induced mechanical allodynia was comparable between age groups. Significant increase of microglia cell numbers was detected in 3, but not 15- and 22-month-old spinal cords. Furthermore, in the zymosan model of acute inflammation, mechanical allodynia was attenuated, and microglial response was less robust in 22 compared to 3-month-old mice. This study suggests that nocifensive responses to damaging stimuli are altered with advancing age and microglial response to peripheral damage is less robust.
authors.affiliation: Wolfson Centre for Age-Related Diseases, King's College London, Guy's Campus, London Bridge, London, SE1 1UL, UK.
authors.forename: Andrea C
authors.initials: AC
authors.lastname: Ogbonna
authors.forename: Anna K
authors.initials: AK
authors.lastname: Clark
authors.forename: Marzia
authors.initials: M
authors.lastname: Malcangio
mesh_terms: D000375:Aging / Q000473:pathology*; D000818:Animals; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000473:pathology*; D001522:Behavior, Animal; D007150:Immunohistochemistry; D007249:Inflammation / Q000473:pathology; D019807:Iodoacetic Acid; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000473:pathology; D020370:Osteoarthritis, Knee / Q000473:pathology*; D010812:Physical Stimulation; D013116:Spinal Cord / Q000166:cytology / Q000473:pathology; D016474:Weight-Bearing
chemical_list: D019807:Iodoacetic Acid