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Changes in dorsal root ganglion CGRP expression in a chronic inflammatory model of the rat knee joint: differential modulation by rofecoxib and paracetamol.
Eur J Pain. 2007 Apr; 11(3):283-9.EJ

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.

Authors+Show Affiliations

Pain Research Department, Neurology and GI Centre of Excellence for Drug Discovery, GlaxoSmithKline Research and Development Ltd., New Frontiers Science Park, Third Avenue, Harlow, Essex, CM19 5AW, United Kingdom. Penny.C.Staton@gsk.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

16690336

Citation

Staton, Penny C., et al. "Changes in Dorsal Root Ganglion CGRP Expression in a Chronic Inflammatory Model of the Rat Knee Joint: Differential Modulation By Rofecoxib and Paracetamol." European Journal of Pain (London, England), vol. 11, no. 3, 2007, pp. 283-9.
Staton PC, Wilson AW, Bountra C, et al. Changes in dorsal root ganglion CGRP expression in a chronic inflammatory model of the rat knee joint: differential modulation by rofecoxib and paracetamol. Eur J Pain. 2007;11(3):283-9.
Staton, P. C., Wilson, A. W., Bountra, C., Chessell, I. P., & Day, N. C. (2007). Changes in dorsal root ganglion CGRP expression in a chronic inflammatory model of the rat knee joint: differential modulation by rofecoxib and paracetamol. European Journal of Pain (London, England), 11(3), 283-9.
Staton PC, et al. Changes in Dorsal Root Ganglion CGRP Expression in a Chronic Inflammatory Model of the Rat Knee Joint: Differential Modulation By Rofecoxib and Paracetamol. Eur J Pain. 2007;11(3):283-9. PubMed PMID: 16690336.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Changes in dorsal root ganglion CGRP expression in a chronic inflammatory model of the rat knee joint: differential modulation by rofecoxib and paracetamol. AU - Staton,Penny C, AU - Wilson,Alex W, AU - Bountra,Chas, AU - Chessell,Iain P, AU - Day,Nicola C, Y1 - 2006/05/11/ PY - 2005/12/08/received PY - 2006/03/09/revised PY - 2006/03/27/accepted PY - 2006/5/13/pubmed PY - 2007/4/20/medline PY - 2006/5/13/entrez SP - 283 EP - 9 JF - European journal of pain (London, England) JO - Eur J Pain VL - 11 IS - 3 N2 - 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. SN - 1090-3801 UR - https://www.unboundmedicine.com/medline/citation/16690336/Changes_in_dorsal_root_ganglion_CGRP_expression_in_a_chronic_inflammatory_model_of_the_rat_knee_joint:_differential_modulation_by_rofecoxib_and_paracetamol_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1090-3801(06)00056-5 DB - PRIME DP - Unbound Medicine ER -