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.
1. The respiratory and psychomotor effects of two benzodiazepines used mainly as anticonvulsants were compared in healthy volunteers, using a double‐blind placebo controlled design. 2. Clobazam (10 and 20 mg) produced significantly fewer psychomotor side effects than clonazepam (0.5 and 1 mg). Neither drug at either dose affected the ventilatory response to CO2. 3. Although clonazepam produced significant effects on psychomotor performance, these did not correlate with plasma drug concentration. 4. Our studies provide further evidence that at the doses chosen clobazam is considerably less sedating than clonazepam. Further investigation is required into the tolerance profile of both drugs in patients.
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