Glial activation in the collagenase model of nociception associated with osteoarthritis.
Background Experimental osteoarthritis entails neuropathic-like changes in dorsal root ganglia (DRG) neurons. Since glial activation has emerged as a key player in nociception, being reported in numerous models of neuropathic pain, we aimed at evaluating if glial cell activation may also occur in the DRG and spinal cord of rats with osteoarthritis induced by intra-articular injection of collagenase. Methods Osteoarthritis was induced by two injections, separated by three days, of 500 U of type II collagenase into the knee joint of rats. Movement-induced nociception was evaluated by the Knee-Bend and CatWalk tests during the following six weeks. Glial fibrillary acidic protein (GFAP) expression in satellite glial cells of the DRG was assessed by immunofluorescence and Western Blot analysis; the pattern of GFAP and activating transcription factor-3 (ATF-3) expression was also compared through double immunofluorescence analysis. GFAP expression in astrocytes and IBA-1 expression in microglia of the L3-L5 spinal cord segments was assessed by immunohistochemistry and Western Blot analysis. The effect of the intrathecal administration of fluorocitrate, an inhibitor of glial activation, on movement-induced nociception was evaluated six weeks after the first collagenase injection. Results GFAP expression in satellite glial cells of collagenase-injected animals was significantly increased six weeks after osteoarthritis induction. Double immunofluorescence showed GFAP upregulation in satellite glial cells surrounding ATF-3-positive neurons. In the spinal cord of collagenase-injected animals, an ipsilateral upregulation of GFAP and IBA-1 was also observed. The inhibition of glial activation with fluorocitrate decreased movement- and loading-induced nociception. Conclusion Collagenase-induced knee osteoarthritis leads to the development of nociception associated with movement of the affected joint and to the activation of glial cells in both the DRG and the spinal cord. Inhibition of glial cell activation by fluorocitrate decreases these osteoarthritis-associated nociceptive behaviours. These results suggest that glial cell activation may play a role in the development of chronic pain in this experimental model of osteoarthritis.
1 Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.|2 Morphysiology of the Somatosensory System Group, Instituto de Biologia Molecular e Celular, Porto, Portugal.|3 Departamento de Biologia Experimental, Faculdade de Medicina da Universidade do Porto, Porto, Portugal.
Sara
S
Adães
1 Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.|2 Morphysiology of the Somatosensory System Group, Instituto de Biologia Molecular e Celular, Porto, Portugal.|3 Departamento de Biologia Experimental, Faculdade de Medicina da Universidade do Porto, Porto, Portugal.
Lígia
L
Almeida
1 Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.|2 Morphysiology of the Somatosensory System Group, Instituto de Biologia Molecular e Celular, Porto, Portugal.|3 Departamento de Biologia Experimental, Faculdade de Medicina da Universidade do Porto, Porto, Portugal.
Catarina S
CS
Potes
1 Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.
Ana Rita
AR
Ferreira
1 Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.|2 Morphysiology of the Somatosensory System Group, Instituto de Biologia Molecular e Celular, Porto, Portugal.|3 Departamento de Biologia Experimental, Faculdade de Medicina da Universidade do Porto, Porto, Portugal.
José M
JM
Castro-Lopes
1 Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.|2 Morphysiology of the Somatosensory System Group, Instituto de Biologia Molecular e Celular, Porto, Portugal.|3 Departamento de Biologia Experimental, Faculdade de Medicina da Universidade do Porto, Porto, Portugal.
Joana
J
Ferreira-Gomes
1 Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.|2 Morphysiology of the Somatosensory System Group, Instituto de Biologia Molecular e Celular, Porto, Portugal.|3 Departamento de Biologia Experimental, Faculdade de Medicina da Universidade do Porto, Porto, Portugal.
Fani L
FL
Neto
D051700:Activating Transcription Factor 3 / Q000378:metabolism; D000818:Animals; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002951:Citrates / Q000627:therapeutic use; D004195:Disease Models, Animal; D005727:Ganglia, Spinal / Q000473:pathology; D005904:Glial Fibrillary Acidic Protein; D008297:Male; D020784:Matrix Metalloproteinase 8 / Q000633:toxicity*; D008840:Microfilament Proteins / Q000378:metabolism; D009068:Movement / Q000502:physiology; D009437:Neuralgia / Q000209:etiology*; D009457:Neuroglia / Q000473:pathology*; D059225:Nociception / Q000187:drug effects / Q000502:physiology*; D010003:Osteoarthritis / Q000139:chemically induced* / Q000150:complications* / Q000188:drug therapy; D051381:Rats; D017208:Rats, Wistar; D018709:Statistics, Nonparametric
D051700:Activating Transcription Factor 3; C100745:Aif1 protein, rat; C497108:Atf3 protein, rat; D002135:Calcium-Binding Proteins; D002951:Citrates; D005904:Glial Fibrillary Acidic Protein; D008840:Microfilament Proteins; C007744:fluorocitrate; D020784:Matrix Metalloproteinase 8
animal model; astrocytes; fluorocitrate; microglia; satellite glial cells