Chronic secondary hypersensitivity of dorsal horn neurones following inflammation of the knee joint.
Intra-articular injection of Freund's complete adjuvant (FCA) into the rat knee joint produces a swelling of the joint and long lasting hypersensitivity. In this study we have used this model and in vivo electrophysiology to investigate the time course of spinal changes underlying chronic secondary hypersensitivity, by stimulating the ankle joint (an area outside the site of primary hypersensitivity), and have compared the results with behavioural data from the same population of animals at 4-8, 13-17 and 55-59 days following FCA injection. The magnitude of responses and the proportion of dorsal horn neurones receiving inputs from A beta- A delta- and C-fibre afferents were monitored. At all time points, there was a significant increase in the ongoing activity of deep dorsal horn neurones when compared to nai ve rats, correlating well with the behavioural hypersensitivity. Both the magnitude of neuronal responses, and the proportion of neurones responding to electrical or mechanical stimulation in an area of secondary hypersensitivity, were significantly increased 4-8 and 13-17 days following FCA injection. However, while there was still behavioural hypersensitivity at 55-59 days there was a substantial decline in the responses to mechanical stimulation and A-fibre responses to electrical stimulation, although the proportion of neurones responding in the C-fibre latency remained elevated. These results suggest that the behavioural hypersensitivity is due to hyperexcitability at the level of the dorsal horn reflected as an increase of both C-fibre responses and spontaneous activity.
Martindale
J C
JC
Pain Research, Neurology and GI Centre of Excellence for Drug Discovery, GlaxoSmithKline, New Frontiers Science Park, Third Avenue, Harlow, Essex CM19 5AW, UK. Jo.C.Martindale@GSK.com
Wilson
A W
AW
Reeve
A J
AJ
Chessell
I P
IP
Headley
P M
PM
D000818:Animals; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000150:complications* / Q000473:pathology*; D001522:Behavior, Animal; D004195:Disease Models, Animal; D005620:Freund's Adjuvant; D007839:Functional Laterality; D006930:Hyperalgesia / Q000209:etiology* / Q000473:pathology*; D007719:Knee Joint / Q000187:drug effects / Q000473:pathology*; D008297:Male; D020671:Posterior Horn Cells / Q000503:physiopathology*; D051381:Rats; D013997:Time Factors
D005620:Freund's Adjuvant