Capsaicin-evoked substance P release in rat dorsal horn increases after peripheral inflammation: a microdialysis study.
Numerous in vitro studies suggest that inflammation is associated with enhanced release of substance P (SP) in the dorsal horn. To test the hypothesis that inflammation increases the evoked concentration of SP in the intact animal, we used in vivo microdialysis with a highly sensitive radioimmunoassay to monitor SP-like immunoreactivity (SP-LI) in the dorsal horn. Seven days after the induction of persistent unilateral inflammation with hindpaw injection of complete Freund's adjuvant, perfusion of the microdialysis probe with 10 microM capsaicin (a concentration which failed to induce SP-LI release in rats without inflammation) induced a significant increase of microdialysate SP-LI. Inclusion of an NMDA antagonist in the perfusion fluid completely blocked this capsaicin-evoked SP release. Administration of a five-fold higher dose of capsaicin did not further increase SP release. These results in a rat model of chronic arthritis suggest that persistent inflammatory signaling facilitates capsaicin-evoked SP release in the dorsal horn in vivo.
Warsame Afrah
Abdullahi
A
Division of Pharmacological Pain Research, Department of Physiology and Pharmacology, Karolinska Institutet, S-17177 Stockholm, Sweden.
Gustafsson
Henrik
H
Olgart
Leif
L
Brodin
Ernst
E
Stiller
Carl-Olav
CO
Taylor
Bradley K
BK
D000818:Animals; D002211:Capsaicin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005620:Freund's Adjuvant; D008297:Male; D017551:Microdialysis / Q000379:methods*; D020078:Neurogenic Inflammation / Q000139:chemically induced / Q000378:metabolism*; D020671:Posterior Horn Cells / Q000187:drug effects* / Q000378:metabolism; D011863:Radioimmunoassay / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000166:cytology*; D013373:Substance P / Q000378:metabolism*; D013997:Time Factors; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology
D018690:Excitatory Amino Acid Agonists; D013373:Substance P; C056639:2-amino-5-phosphopentanoic acid; D005620:Freund's Adjuvant; D014633:Valine; D002211:Capsaicin