Anti-inflammatory effects of contralateral administration of the kappa-opioid agonist U-50,488H in rats with unilaterally induced adjuvant arthritis.
OBJECTIVE
The effect of repeated contralateral treatment with the kappa-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 kappa-opioid receptor agonist diminishes the development of a symmetrical joint disorder.
Bileviciute-Ljungar
I
I
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden. indre.ljungar@ds.se
Saxne
T
T
Spetea
M
M
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000008:administration & dosage / Q000627:therapeutic use*; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D000843:Ankle Joint / Q000473:pathology; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001169:Arthritis, Experimental / Q000473:pathology / Q000517:prevention & control*; D001835:Body Weight; D004334:Drug Administration Schedule; D004487:Edema / Q000188:drug therapy / Q000473:pathology; D005260:Female; D006614:Hindlimb / Q000473:pathology; D010146:Pain / Q000517:prevention & control; D010147:Pain Measurement; D051381:Rats; D011917:Rats, Inbred Lew; D017473:Receptors, Opioid, kappa / Q000819:agonists; D012720:Severity of Illness Index
D018712:Analgesics, Non-Narcotic; D018501:Antirheumatic Agents; D017473:Receptors, Opioid, kappa; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer