Chronic secondary hypersensitivity of dorsal horn neurones following inflammation of the knee joint

Abstract 

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 timecourse 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 55–59days following FCA injection. The magnitude of responses and the proportion of dorsal horn neurones receiving inputs from Aβ- Aδ- and C-fibre afferents were monitored. At all timepoints, there was a significant increase in the ongoing activity of deep dorsal horn neurones when compared to naı¨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 13–17days following FCA injection. However, while there was still behavioural hypersensitivity at 55–59days 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.

Keywords: Joint inflammation, In vivo electrophysiology, Dorsal horn, Central sensitisation, Secondary hypersensitivity