Capsaicin receptors are expressed in primary sensory neurons and excited by heat and protons. We examined the in¯ammation-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 in¯ammation, 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 in¯ammation induces the axonal transport of VR1 mRNA, which may be involved in the hypersensitivity of primary afferents to capsaicin and the production of in¯ammatory hyperalgesia. Keywords: axonal transport, capsaicin sensitivity, carrageenan in¯ammation, glutamate release, primary afferent, VR1 capsaicin receptor mRNA.Subcutaneous injection of carrageenan into the hind paw induces in¯ammation, a decrease in nociceptive threshold (Kayser et al. 1991) and hyperexcitability of primary afferents (Coggeshall et al. 1983). Nociceptive primary afferents are sensitive to capsaicin. Capsaicin induces the excitation of nociceptors (Such and Jancso 1986; Holzer 1991) and the release of pain transmitters such as glutamate (Ueda et al. 1993; and neuropeptides (Yaksh et al. 1980;Saria et al. 1986). Capsaicin receptor is called a`proton sensor' and`hot sensor' because of its sensitivity to protons and heat stimulation, respectively (Caterina et al. 1997). When in¯ammation occurs in the periphery, the concentration of protons is increased in injured tissues. Therefore, the activation of capsaicin receptors on the peripheral terminals of primary afferents may be partly involved in in¯ammatory hyperalgesia (Caterina et al. 2000). With regard to the spinal cord, glutamate (Okano et al. 1998) and neuropeptides (Satoh et al. 1992;Okano et al. 1998) are also involved in in¯ammatory hyperalgesia. Peripheral in¯ammation increases capsaicin-evoked release of glutamate and neuropeptides ) from the dorsal horn. Although an increase in the biosynthesis of neurotransmitters in primary sensory neurons may be partly responsible for an increase in capsaicin-evoked release of the neurotransmitters Ohno et al. 1990), it is unclear whether peripheral in¯ammation alters, especially increases, the sensitivity of primary afferent
Attention has recently been paid to the duodenum as the pathophysiologic center of functional dyspepsia. However, the precise mechanisms of symptom generation remain unknown. We here investigated the effect of acid on duodenal prostaglandin E 2 and localization of prostaglandin E 2 related receptors. Sprague-Dawley rats were used for this study. Hydrochloric acid was administered in the duodenum, then prostaglandin E 2 levels in the duodenum were measured using the ELISA. The expression and localization of prostaglandin receptors (EP1-4) and the mRNAs of prostaglandin synthases were investigated using in situ hybridization histochemistry in duodenal tissue. After acid perfusion, prostaglandin E 2 levels in the duodenum significantly increased. EP3 was expressed mainly at the myenteric plexus in the duodenal mucosa, and EP4 at both the epithelial surface and myenteric plexus. Contrary, EP2 was sparsely distributed in the villi and EP1 were not clearly seen on in situ hybridization histochemistry. Prostaglandin-synthetic enzymes were also distributed in the duodenal mucosa. The prostaglandin E 2 levels in the duodenum increased after acidification. Prostaglandin E 2 receptors and prostaglandin E 2 -producing enzymes were both observed in rat duodenum. These observations suggest that duodenal prostaglandin E 2 possibly play a role in the symptom generation of functional dyspepsia.
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