Changes in dorsal root ganglion CGRP expression in a chronic inflammatory model of the rat knee joint: Differential modulation by rofecoxib and paracetamol

Abstract

Neuropeptide-expressing small diameter sensory neurones are thought to be vital in generating inflammatory hyperalgesic responses. Within the dorsal root ganglion (DRG), both the levels of the neuropeptide calcitonin gene-related peptide (CGRP) and the numbers of CGRP-immunoreactive (CGRP-IR) DRG neurones have been shown to increase in a number of acute adjuvant-induced inflammatory pain models. The aim of this study was to look specifically at changes in numbers of CGRP-IR DRG neurones in a chronic model of inflammatory joint pain following complete Freund's adjuvant (CFA) injection into the rat knee. In this model, there were significant increases in the number of ipsilateral CGRP-IR small DRG neurones at days 1, 16 and 35 following intra-articular CFA, compared to saline-injected sham animals. This correlated with the behavioural readouts of hypersensitivity and knee joint inflammation at the same time points. There was also a significant increase in the number of ipsilateral CGRP-IR medium DRG neurones and contralateral CGRP-IR small DRG neurones at day 1. Following dosing of CFA-injected rats with rofecoxib (Vioxx) or paracetamol, there was a significant decrease in the number of ipsilateral CGRP-IR small and medium DRG neurones in rofecoxib- but not paracetamol-treated rats. These data also correlated with behavioural readouts where hypersensitivity and knee joint inflammation were significantly reduced by rofecoxib but not paracetamol treatment. In conclusion, these data show that changes in ipsilateral CGRP expression within small DRG neurones are consistent with behavioural readouts in both time course, rofecoxib and paracetamol studies in this model of chronic inflammatory pain.

Efficacy of zoledronic acid in treatment of teoarthritis is dependent on the disease progression stage in rat medial meniscal tear model

“…Osteoarthritic conditions activate the nociceptive system, and CGRP is elevated in the DRGs [25,34] . A decrease in the number of CGRP-positive DRG neurons was also consistent with improved pain behavior [25,35] . In accordance with a previous study, our data show that the percentage of CGRP-positive neurons was markedly increased at advanced stages in the MMT model, whereas ZOL treatment initiated at early stages reduced the expression of CGRP.…”

Neuronal Injury Marker ATF-3 Is Induced in Primary Afferent Neurons of Monoarthritic Rats

“…Additionally, ketoprofen-treated rats showed higher CGRP expression, particularly in the 4d MA+2d Ket group. Staton et al [48] observed decreased CGRP expression following oral administration of rofecoxib to CFA knee-injected rats between days 13 and 17. Separated quantification of small-or medium-sized cells, but particularly the differing treatments (ways of administration and timepoints) may account for the disagreement with our data in MA.…”

Changes in calcitonin gene-related peptide expression following joint immobilization in rats

“…Secondly, changes in CGRP expression within the dorsal root ganglion (DRG) have been studied in various pain models. The number of CGRP-immunoreactive (CGRP-IR) DRG neurons increased or decreased in inflammatory and neuropathic pain models [11,14,21]. In these studies, phenotypic changes in DRG CGRP expression have included both a change in the number of CGRP-IR neurons and a switch to CGRP expression in small or large DRG neurons.…”