Effects of systemic resiniferatoxin treatment on substance P mRNA in rat dorsal root ganglia and substance P receptor mRNA in the spinal dorsal horn.
Capsaicin depletes the sensory neuropeptide substance P (SP) in the rat due to a combination of neuron loss and decreased synthesis in the surviving cells. Resiniferatoxin (RTX) mimics most, but not all, capsaicin actions. In the present study, the effects of RTX (300 microg/kg, s.c.) were examined on mRNA levels for SP and its receptor in the adult rat. The percentage of dorsal root ganglia (DRG) neuronal profiles showing an in situ hybridization signal for preprotachykinin mRNAs encoding SP was not altered following RTX treatment (up to 8 weeks), though the signal became perceptibly weaker. In accord, 2 weeks after RTX administration a 60% decrease was observed in the steady-state levels of SP-encoding mRNAs using Northern blot analysis, leaving the ratio of beta- and gamma-preprotachykinin mRNAs unchanged. No change was, however, observed in mRNA levels encoding tachykinins NK-1 receptors in the dorsal horn, the spinal targets for SP. The present findings suggest that RTX does not kill SP-positive DRG neurons, though it suppresses the synthesis of SP. Since RTX treatment does not alter NK-1 receptor expression, this reduced SP synthesis is likely to play a central role in the analgesic actions of RTX.
Szallasi
A
A
Department of Pharmacology, Karolinska Institute, S-171 77, Stockholm, Sweden.szallasi@exchange.nih.gov
Farkas-Szallasi
T
T
Tucker
J B
JB
Lundberg
J M
JM
Hökfelt
T
T
Krause
J E
JE
D000287:Administration, Topical; D000818:Animals; D002211:Capsaicin / Q000008:administration & dosage; D004224:Diterpenes / Q000008:administration & dosage*; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism*; D017403:In Situ Hybridization; D007279:Injections, Subcutaneous; D008297:Male; D064729:Neurokinin-1 Receptor Antagonists; D009498:Neurotoxins / Q000008:administration & dosage*; D059408:Pain Management; D011498:Protein Precursors / Q000235:genetics; D012333:RNA, Messenger / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018040:Receptors, Neurokinin-1 / Q000235:genetics / Q000378:metabolism*; D012260:Ribonucleases / Q000378:metabolism; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*; D013373:Substance P / Q000037:antagonists & inhibitors / Q000235:genetics*; D015320:Tachykinins / Q000235:genetics
D004224:Diterpenes; D064729:Neurokinin-1 Receptor Antagonists; D009498:Neurotoxins; D011498:Protein Precursors; D012333:RNA, Messenger; D018040:Receptors, Neurokinin-1; D015320:Tachykinins; C044206:preprotachykinin; D013373:Substance P; C024353:resiniferatoxin; D012260:Ribonucleases; D002211:Capsaicin