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 nociceptive processing during the formalin test. However, no direct measurement of the temporal changes in substance P levels within the spinal cord of conscious animals has been reported. Further, dissociation between substance P levels and formalin-evoked nocifensive behavior may exist in diabetic rats, as exaggerated hyperalgesic behavior coexists with reduced peripheral nerve substance P levels. The present study was performed to directly measure the appearance of substance-P-like immunoreactivity (SP-LI) in spinal CSF of conscious, unrestrained rats using microdialysis techniques following injection of formalin into the hindpaw. The effect of diabetes upon formalin-evoked SP-LI levels in spinal CSF dialysates was also determined. In control 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 rats exhibited reduced (p<0.05) SP-LI in their spinal roots, while basal levels in spinal CSF were not different from controls. Formalin-evoked nocifensive behavior was increased in diabetic rats but SP-LI levels in spinal CSF dialysates after paw formalin injection were significantly (p<0.05) attenuated, reaching a maximum of only 161% of basal levels. This was accompanied by attenuated swelling at the formalin injection site and increased thermal response latencies. While increased SP-LI in spinal CSF coincides with phase 2 behavior in the formalin test and may contribute to spinal nociceptive processing during this period, exaggerated spinal substance P release is unlikely to underlie the increased nocifensive behavior seen in diabetic rats.
Calcutt
N A
NA
Department of Pathology, University of California San Diego, La Jolla, CA, USA. ncalcutt@ucsd.edu
Stiller
C
C
Gustafsson
H
H
Malmberg
A B
AB
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000134:cerebrospinal fluid / Q000503:physiopathology*; D005260:Female; D005557:Formaldehyde / Q000633:toxicity; D006614:Hindlimb; D006358:Hot Temperature; D010146:Pain / Q000139:chemically induced / Q000503:physiopathology*; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D013373:Substance P / Q000134:cerebrospinal fluid / Q000378:metabolism*
D001786:Blood Glucose; D005557:Formaldehyde; D013373:Substance P