A quantitative approach to measure joint pain in experimental osteoarthritis--evidence of a role for nitric oxide.
OBJECTIVE
To describe a method to study joint pain in experimental osteoarthritis (OA) and to study nitric oxide (NO) participation in experimental OA.


METHODS
Rats were subjected to anterior cruciate ligament transection (ACLT) (OA group) of the right knee and evaluated during 28 days. A sham group was false operated and a naive group received no manipulation. Joint pain was measured by recording the time the right hind paw fails to touch the surface while walking. Cell influx (CI) and nitrite levels were measured in joint exudates. Expression of inducible NO synthase (iNOS) in synovia was detected by immunostaining. For the specific purpose of pharmacological manipulation, groups received either indomethacin (2 mg/kg/day s.c. (subcutaneous)), meloxicam (6 mg/kg/day s.c.), morphine (200 microg intra-articularly), the non-selective NOS inhibitor L-N(G)-nitroarginine methyl ester (L-NAME; 30 mg/kg/bid i.p. (intra-peritoneal)) or the selective iNOS inhibitor 1400W (0.5 mg/kg/day s.c.), given 30 min prior (prophylactic) or 4 days after (therapeutic) ACLT, until sacrifice, at 7 days. The respective non-treated groups received the vehicles.


RESULTS
The OA group developed joint pain, as compared to sham and control groups (P<0.05). Significantly increased nitrite levels and iNOS immunostaining were seen in the OA group. Both indomethacin and meloxicam inhibited joint pain (P<0.05). Morphine inhibited joint pain, whereas this effect was blocked by co-administration of the mu-opioid receptor naloxone. CI was similar among all groups. Prophylactic but not therapeutic L-NAME or 1400W reduced joint pain.


CONCLUSIONS
We describe a method to quantitate joint pain associated to weight bearing in the ACLT model. The joint pain is sensitive to classical antinociceptive compounds. NO release is associated to joint pain though NOS inhibition does not inhibit ongoing pain.
Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Brazil.
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Castro
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Cunha
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Silva
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Rocha
D000578:Amidines / Q000494:pharmacology; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D018771:Arthralgia / Q000188:drug therapy / Q000209:etiology*; D001596:Benzylamines / Q000494:pharmacology; D005122:Exudates and Transudates / Q000737:chemistry; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D000077239:Meloxicam; D023421:Models, Animal; D009020:Morphine / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052247:Nitric Oxide Synthase Type II / Q000032:analysis / Q000037:antagonists & inhibitors; D009573:Nitrites / Q000032:analysis; D010003:Osteoarthritis / Q000378:metabolism / Q000523:psychology*; D051381:Rats; D017208:Rats, Wistar; D013314:Stress, Mechanical; D013583:Synovial Membrane / Q000378:metabolism*; D013843:Thiazines / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology
D000578:Amidines; D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001596:Benzylamines; C104820:N-(3-(aminomethyl)benzyl)acetamidine; D009573:Nitrites; D013843:Thiazines; D013844:Thiazoles; D009569:Nitric Oxide; D009020:Morphine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D019331:NG-Nitroarginine Methyl Ester; D000077239:Meloxicam; D007213:Indomethacin