Axonal transport of VR1 capsaicin receptor mRNA in primary afferents and its participation in inflammation-induced increase in capsaicin sensitivity.
Capsaicin receptors are expressed in primary sensory neurons and excited by heat and protons. We examined the inflammation-induced changes of the level of VR1 capsaicin receptor mRNA in sensory neurons and the sensitivity of primary afferents to capsaicin. Carrageenan treatment induced axonal transport of VR1 mRNA, but not that of preprotachykinin mRNA, from the dorsal root ganglia to central and peripheral axon terminals. The sensitivity of central terminals to capsaicin, which was estimated by measuring the capsaicin-evoked release of glutamate from the dorsal horn, was increased by peripheral inflammation, and such an increase was suppressed by inhibiting the RNA translation in the dorsal horn with cycloheximide and an intrathecal injection of VR1 antisense oligonucleotides. Thus, peripheral inflammation induces the axonal transport of VR1 mRNA, which may be involved in the hypersensitivity of primary afferents to capsaicin and the production of inflammatory hyperalgesia.
Research Center for Ethnomedicines, Institute of Natural Medicine, Toyama Medical and Pharmaceutical University, Toyama, Japan.
C
C
Tohda
M
M
Sasaki
T
T
Konemura
T
T
Sasamura
M
M
Itoh
Y
Y
Kuraishi
D000344:Afferent Pathways / Q000502:physiology* / Q000503:physiopathology; D000818:Animals; D001370:Axonal Transport; D002211:Capsaicin / Q000493:pharmacokinetics / Q000494:pharmacology*; D003078:Colchicine / Q000494:pharmacology; D007839:Functional Laterality; D005727:Ganglia, Spinal / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation; D006930:Hyperalgesia / Q000503:physiopathology; D007249:Inflammation / Q000503:physiopathology*; D008297:Male; D009411:Nerve Endings / Q000187:drug effects / Q000502:physiology; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology; D010146:Pain / Q000503:physiopathology*; D020671:Posterior Horn Cells / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011955:Receptors, Drug / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012584:Sciatic Nerve / Q000502:physiology*; D014158:Transcription, Genetic
D020319:Oligodeoxyribonucleotides, Antisense; D012333:RNA, Messenger; D011955:Receptors, Drug; D002211:Capsaicin; D003078:Colchicine