Elevated substance-P-like immunoreactivity levels in spinal dialysates during the formalin test in normal and diabetic rats

Pharmacologic studies implicate the involvement of substance P in spinal no ciceptive processing during the formalin test. However, no direct measureme nt of the temporal changes in substance P levels within the spinal cord of conscious animals has been reported. Further, dissociation between substanc e P levels and formalin-evoked nocifensive behavior may exist in diabetic r ats, as exaggerated hyperalgesic behavior coexists with reduced peripheral nerve substance P levels. The present study was performed to directly measu re the appearance of substance-P-like immunoreactivity (SP-LI) in spinal CS F of conscious, unrestrained rats using microdialysis techniques following injection of formalin into the hindpaw. The effect of diabetes upon formali n-evoked SP-LI levels in spinal CSF dialysates was also determined. In cont rol rats, SP-LI increased in spinal dialysates following formalin injection and levels were maximal 20-30 min after injection, rising to 325% of basal values (p < 0.02). Diabetic mts exhibited reduced (p < 0.05) SP-LI in thei r spinal roots, while basal levels in spinal CSF were not different from co ntrols. Formalin-evoked nocifensive behavior was increased in diabetic rats but SP-LI levels in spinal CSF dialysates after paw formalin injection wer e significantly (p < 0.05) attenuated, reaching a maximum of only 161% of b asal levels. This was accompanied by attenuated swelling at the formalin in jection site and increased thermal response latencies. While increased SP-L I in spinal CSF coincides with phase 2 behavior in the formalin test and ma p contribute to spinal nociceptive processing during this period, exaggerat ed spinal substance P release is unlikely to underlie the increased nocifen sive behavior seen in diabetic rats. (C) 2000 Elsevier Science B.V. All rig hts reserved.