Rheumatology Advance Access originally published online on October 25, 2005
Rheumatology 2006 45(3):295-302; doi:10.1093/rheumatology/kei156
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Anti-inflammatory effects of contralateral administration of the 
-opioid agonist U-50,488H in rats with unilaterally induced adjuvant arthritis
1 Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden, 2 Department of Surgical Sciences, Section of Orthopaedics, Karolinska Institutet, Orthopaedic Research Laboratory M3:02, Karolinska Hospital, Stockholm, Sweden, 3 Department of Rheumatology, Lund University Hospital, Lund, Sweden and 4 Department of Pharmaceutical Chemistry, Institute of Pharmacy and Center for Molecular Biosciences Innsbruck, University of Innsbruck, Austria. 5 Present address: University Clinic of Rehabilitation Medicine Stockholm, Danderyd Hospital, Building 32, 182 88 Stockholm, Sweden.
Correspondence to: I. Bileviciute-Ljungar, University Clinic of Rehabilitation Medicine Stockholm, Danderyd Hospital, Building 32, 182 88 Stockholm, Sweden. E-mail: indre.ljungar{at}ds.se
Objective. The effect of repeated contralateral treatment with the 
-opioid receptor agonist U-50,488H {trans-(±)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]-benzene acetamide methanesulphonate} was investigated in rats with unilaterally induced adjuvant arthritis.
Methods. Arthritis was induced by injection of Mycobacterium butyricum into the right hindpaw. Inflammatory parameters, nociceptive behaviour and cartilage turnover were evaluated up to 21 days after induction of arthritis.
Results. Contralateral treatment with 0.3 mg U-50,488H into the left hindpaw twice per week reduced the hindpaw oedema, ankle joint inflammation, pain behaviour to mechanical stimuli and severity score of inflammation in the hindpaws of both sides as well as the systemic spread of inflammation to other areas, e.g. tail and/or forepaws, compared with saline-treated animals. Moreover, a significant decrease in the levels of cartilage oligomeric matrix protein was found in animals treated with U-50,488H, suggesting reduction of cartilage damage. The anti-inflammatory and chondroprotective effects of U-50,488H were abolished by administration of the peripheral opioid receptor antagonist naloxone methiodide.
Conclusions. This is the first report demonstrating that repeated contralateral administration of a -opioid receptor agonist diminishes the development of a symmetrical joint disorder.
KEY WORDS: Contralateral treatment, -Opioid agonist, U-50, 488H, Cartilage oligomeric matrix protein, Adjuvant arthritis, Rats