Changes in dorsal root ganglion CGRP expression in a chronic inflammatory model of the rat knee joint: differential modulation by rofecoxib and paracetamol.
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.
Staton
Penny C
PC
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.com
Wilson
Alex W
AW
Bountra
Chas
C
Chessell
Iain P
IP
Day
Nicola C
NC
D000082:Acetaminophen / Q000494:pharmacology*; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology; D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D048429:Cell Size; D002908:Chronic Disease; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D004195:Disease Models, Animal; D005620:Freund's Adjuvant; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism*; D006930:Hyperalgesia / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D007150:Immunohistochemistry; D007783:Lactones / Q000494:pharmacology*; D008297:Male; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism; D020370:Osteoarthritis, Knee / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D051381:Rats; D013450:Sulfones / Q000494:pharmacology*
D018712:Analgesics, Non-Narcotic; D052246:Cyclooxygenase 2 Inhibitors; D007783:Lactones; D013450:Sulfones; C116926:rofecoxib; D000082:Acetaminophen; D005620:Freund's Adjuvant; D015740:Calcitonin Gene-Related Peptide