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.
Simjee
Shabana U
SU
School of Biological Sciences, The University of Manchester, Oxford Road, Manchester M13 9PT, UK University Dental Hospital of Manchester, Higher Cambridge Street, Manchester M15 6FH, UK.
Pleuvry
Barbara J
BJ
Coulthard
Paul
P
D000818:Animals; D018771:Arthralgia / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D001169:Arthritis, Experimental / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D018682:GABA Agents / Q000494:pharmacology* / Q000627:therapeutic use; D018755:GABA Agonists / Q000494:pharmacology / Q000627:therapeutic use; D018756:GABA Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D058787:GABA-A Receptor Antagonists; D007596:Joints / Q000187:drug effects / Q000294:innervation / Q000503:physiopathology; D007794:Lameness, Animal / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D009118:Muscimol / Q000494:pharmacology / Q000627:therapeutic use; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D010523:Peripheral Nervous System Diseases / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D051381:Rats; D011917:Rats, Inbred Lew; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D011963:Receptors, GABA-A / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D018682:GABA Agents; D018755:GABA Agonists; D018756:GABA Antagonists; D058787:GABA-A Receptor Antagonists; D011963:Receptors, GABA-A; D009118:Muscimol; D005680:gamma-Aminobutyric Acid