Effect of streptozotocin-diabetes on knee joint inflammation-induced changes in substance P and nerve growth factor in the rat

Abstract

Given the involvement of the sensory nervous system in the aetiology of neurogenic inflammation, we have investigated the effect of experimental diabetes and any associated sensory nerve dysfunction on the development of complete Freund's adjuvant-induced inflammation in the rat knee. Twenty-four hours after induction of inflammation in non-diabetic rats, γ-preprotachykinin mRNA expression was increased in the L 4/L 5 dorsal root ganglia. Substance P levels were increased in dorsal root ganglia and sciatic nerve whilst synovial levels of substance P were significantly decreased. Nerve growth factor, which regulates expression of γ-preprotachykinin mRNA, was significantly increased in synovium and sciatic nerve after induction of inflammation. After 24 weeks of streptozotocin-diabetes, there was a non-significant reduction in γ-preprotachykinin mRNA expression whilst substance P levels in dorsal root ganglia, sciatic nerve and synovium and nerve growth factor levels in the sciatic nerve were significantly decreased. Conversely, synovial levels of nerve growth factor were significantly increased. Injection of complete Freund's adjuvant into the knee of diabetic 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 significantly increased in synovium and sciatic nerve suggesting an uncoupling 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-diabetes. Deficits in γ-preprotachykinin mRNA expression and substance P and the altered levels of nerve growth factor indicate sensory neuronal dysfunction may play a major role in this abnormal response.