EFFECT OF STREPTOZOTOCIN-DIABETES ON KNEE-JOINT INFLAMMATION-INDUCED CHANGES IN SUBSTANCE-P AND NERVE GROWTH-FACTOR IN THE RAT

Given the involvement of the sensory nervous system in the aetiology o f neurogenic inflammation, we have investigated the effect of experime ntal diabetes and any associated sensory nerve dysfunction on the deve lopment of complete Freund's adjuvant-induced inflammation in the rat knee. Twenty-four hours after induction of inflammation in non-diabeti c rats, gamma-preprotachykinin mRNA expression was increased in the L( 4)/L(5) dorsal root ganglia. Substance P levels were increased in dors al root ganglia and sciatic nerve whilst synovial levels of substance P were significantly decreased. Nerve growth factor, which regulates e xpression of gamma-preprotachykinin mRNA, was significantly increased in synovium and sciatic nerve after induction of inflammation. After 2 4 weeks of streptozotocin-diabetes, there was a non-significant reduct ion in gamma-preprotachykinin mRNA expression whilst substance P level s in dorsal root ganglia, sciatic nerve and synovium and nerve growth factor levels in the sciatic nerve were significantly decreased. Conve rsely, synovial levels of nerve growth factor were significantly incre ased. Injection of complete Freund's adjuvant into the knee of diabeti c rats produced diminished joint swelling compared to that observed in non-diabetic rats. Substance P levels were unaltered compared to non- arthritic diabetic rats whilst nerve growth factor levels were signifi cantly increased in synovium and sciatic nerve suggesting an uncouplin g of substance P from nerve growth factor control in the inflammatory response in diabetic rats. The results show a significant reduction in the inflammatory response in rats with chronic streptozotocin-diabete s. Deficits in gamma-preprotachykinin mRNA expression and substance P and the altered levels of nerve growth factor indicate sensory neurona l dysfunction may play a major role in this abnormal response.