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

Abstract

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.

The use of motion analysis to measure pain-related behaviour in a rat model of degenerative tendon injuries

“…The observed increase in DS as an indicator of pain was consistent to previous reports on inflammatory pain (Coulthard, 2002;Coulthard, 2003;Simjee 2004), which was explained as an adaptive mechanism to reduce mechanical agitation to the injured limb to avoid pain.…”

“…Significant changes in the gait parameters of the contralateral limbs in collagenase-treated rats suggested adaptive motions to reduce mechanical allodynia in the injured limbs. Our results indicate that motion analysis was useful for the detection of knee pain associated with patellar tendon injuries at longer time points post injury as compared to previous studies which worked on relatively short-term inflammatory pain (Coulthard, 2003), Achilles tendon injuries (Messner, 1999) or arthritic knee (Simjee 2004). …”

“…Analysis of ankle data would further increase number of comparisons on the same set of data. Previous studies on animal gait (Coulthard, 2002;Coulthard, 2003;Simjee 2004) also faced the same problem of multiple comparisons, Page 21 of 37 A c c e p t e d M a n u s c r i p t 20 but adjustments were made only to multiple 2-group comparisons. In our study, we analyzed the data with MANOVA and ANOVA with repeated measures but post hoc multiple group comparisons were not performed.…”

“…However, there was no clear distinction between the two in previous reports (Coulthard, 2002;Coulthard, 2003). Since DS is identified as a sensitive parameter to characterize pain (Simjee, 2004), it is necessary to distinguish the two for the use of DS as a valid measurement for pain. Thirdly, the influences of repeated measurements as training effect were evaluated when comparing the results of follow-up study with those of end-point measurement.…”

Inflammation-Induced Reduction of Spontaneous Activity by Adjuvant: A Novel Model to Study the Effect of Analgesics in Rats

“…However, the predictive utility of this model is currently unknown because it has yet to be validated with standard analgesic agents such as opioids or nonsteroidal anti-inflammatory drugs. The only drug administration paradigms tested by this approach are infusions of muscimol and bicuculline (Simjee et al, 2004). Finally, other approaches being developed to address problems with evoked stimuli have been focusing on cognitive processing; for example, the measurement of nonselective, nonsustained attention in rats with chronic visceral inflammation (Millecamps et al, 2004), and operant escape from a cold stimulus (Vierck et al, 2005).…”