Modulation of the gait deficit in arthritic rats by infusions of muscimol and bicuculline.

Gait analysis in the adjuvant-induced arthritic rat model of chronic pain was used to examine the role of GABA(A) receptors in the development of pain. Drug solutions were administered continuously at 5+/-0.75 microl/h for 14 days via Alzet osmotic pumps (2ML2) placed under the skin of the back. The GABA(A) receptor agonist, muscimol, produces a dose-dependent reversal of the gait deficits seen in arthritic rats without reducing the tibiotarsal joints inflammatory edema or the histological picture of joint erosion and inflammation. The higher infusion rate for muscimol, 20 microg/h, caused the gait for the arthritic rats to be indistinguishable from that of normal non-arthritic rats. In normal, non-arthritic rats, muscimol did not show any effect on gait. The GABA(A) receptor antagonist bicuculline showed small but significant exacerbation of stride length (P < 0.05) single and double stance time (P < 0.05) and swing time deficits (P < 0.05) in the arthritic rats, but no changes in measures of gait in the normal control rat. The results suggest that the development of arthritic pain is increased in the absence of GABA(A) receptor tone and that increasing GABA(A) receptor tone can reduce arthritic pain but does not affect the disease process.

Gait analysis as a correlate of pain induced by carrageenan intraplantar injection.

The aim of this study was to investigate whether gait changes occurring during the development of carrageenan induced rodent paw inflammation could be measured to provide an objective marker of persistent pain. The objectives were to measure hind limb tibiotarsal joint diameter as an indication of inflammatory oedema and to analyse gait during the development of the carrageenan induced persistent pain. Rear paw intraplantar injection of 6 mg (150 microl) lambda-carrageenan resulted in significant swelling of rear limbs at 90 min (P=0.002). Analysis of gait, using video recordings of spontaneous animal ambulations demonstrated significant changes in gait over a 90-min period. These were primarily changes in temporal measures of gait and consisted of a reduction in velocity (P=0.005) and stride length (P=0.006) and increase in dual stance time (P=0.009). It is hypothesised that the temporal and spatial changes in gait observed in this model of acute inflammatory hyperalgesia may have been due to avoidance of the normally non-noxious mechanical stimulation induced by walking. It is suggested that gait analysis may be a suitable method for measuring early behavioural change associated with inflammatory hyperalgesia.

Gait analysis as an objective measure in a chronic pain model.

The aim of this study was to investigate objective characterisation of gait as a marker of the chronic pain of adjuvant arthritis (AA). Video recorded images of spontaneous rat ambulations were analysed to quantify various temporal and spatial parameters and compare these between the AA and control groups. Changes were also recorded after the administration of a single dose of buprenorphine (15 ?g). Individual temporal parameters were significantly reduced (velocity (P=0.05), stride length (P=0.007), single stance time (P<0.001), swing time (P=0.001)), or increased (dual stance time (P<0.001)) at 10 days in the AA group compared to control. The rear paws showed reduced ground contact and the fore paws an increase in proximal pad and decrease in digit area, although these changes were not all statistically significant. Some of the gait parameters showed significant reversal following administration of buprenorphine (velocity (P<0.001) and stride length (P<0.001) were increased and single stance time (P=0.014) reduced). It is proposed that changes in gait are a marker of AA chronic pain in this model. These behavioural changes were significant at a very early stage (day 10), before the development of physical deformities and increase in paw volume and might permit an earlier detection of pain than other models.