Glial activation in the collagenase model of nociception associated with osteoarthritis

Abstract

BackgroundExperimental 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.MethodsOsteoarthritis 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.ResultsGFAP 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.ConclusionCollagenase-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.

TDAG8 deficiency reduces satellite glial number and pro-inflammatory macrophage number to relieve rheumatoid arthritis disease severity and chronic pain

“…Moreover, neuron-glia interactions play a role in the chronic phase. Consistent with previous studies in monoarthritis or osteoarthritis [13,14], our RA mice showed increased number of SGCs. With TDAG8 deficiency, the increased number of SGCs was completely inhibited.…”

“…It suggests that polyarthritis occurred in RA mice. In a monoarthritis model or collagenase arthritis model, arthritic rats showed SGC proliferation and activation [13,14]. To determine whether the number of SGCs was also increased in our RA mice, DRG from RA mice were immunostained for anti-GFAP (a SGC marker).…”

“…In a monoarthritis or collagenase arthritis model, arthritic rats showed satellite glial cell (SGC) proliferation and activation in dorsal root ganglia (DRG) [13,14]. Intrathecal injection of a glial inhibitor (fluorocitrate) blocked collagenase-induced nociception [14], which suggests that SGCs play some roles in arthritic pain. IL-17A may act on glial cells to sensitize neuron function [15].…”

Gait Assessment of Pain and Analgesics: Comparison of the DigiGait™ and CatWalk™ Gait Imaging Systems

“…Another CatWalk ™ study revealed abnormal coordination and intensity data after intraplantar CFA injection [43]. In similar adjuvant-induced mono-arthritis models, CatWalk ™ revealed abnormal gait data [44–54], and the intensity data were highly correlated with punctate allodynia and knee-bend score [55]. Moreover, all gait parameters were partially improved by analgesic therapies [45, 48, 50].…”

Amylin, a peptide expressed by nociceptors, modulates chronic neuropathic pain

“…The acute intrathecal injection aimed at reaching the lumbar spinal segments and was performed according to our protocol (Adaes et al, ) which was adapted from (De la Calle & Paino, ; Ossipov, Suarez, & Spaulding, ). Briefly, rats were anesthetized with isoflurane as described above and the rats’ abdomen‐pelvic region was lifted to create a slight curvature in the vertebral column at vertebral level L5–S1, which was localized using the anterior part of the iliac crest as a tactile reference point for the L6 vertebra.…”