Activation of transient receptor potential vanilloid 1 (TRPV1), a calcium permeable channel expressed in primary sensory neurons, induces the release of glutamate from their central and peripheral afferents during normal acute and pathological pain. However, little information is available regarding the glutamate release mechanism associated with TRPV1 activation in primary sensory neurons. To address this issue, we investigated the expression of vesicular glutamate transporter (VGLUT) in TRPV1-immunopositive (+) neurons in the rat trigeminal ganglion (TG) under normal and complete Freund’s adjuvant (CFA)-induced inflammatory pain conditions using behavioral testing as well as double immunofluorescence staining with antisera against TRPV1 and VGLUT1 or VGLUT2. TRPV1 was primarily expressed in small and medium-sized TG neurons. TRPV1+ neurons constituted approximately 27% of all TG neurons. Among all TRPV1+ neurons, the proportion of TRPV1+ neurons coexpressing VGLUT1 (VGLUT1+/ TRPV1+ neurons) and VGLUT2 (VGLUT2+/TRPV1+ neurons) was 0.4% ± 0.2% and 22.4% ± 2.8%, respectively. The proportion of TRPV1+ and VGLUT2+ neurons was higher in the CFA group than in the control group (TRPV1+ neurons: 31.5% ± 2.5% vs. 26.5% ± 1.2%, VGLUT2+ neurons: 31.8% ± 1.1% vs. 24.6% ± 1.5%, p < 0.05), whereas the proportion of VGLUT1+, VGLUT1+/TRPV1+, and VGLUT2+/TRPV1+ neurons did not differ significantly between the CFA and control groups. These findings together suggest that VGLUT2, a major isoform of VGLUTs, is involved in TRPV1 activation-associated glutamate release during normal acute and inflammatory pain.

Transient receptor potential melastatin 8 (TRPM8) plays a crucial role in innocuous cool sensation, acute cold pain and cold-induced hyperalgesia during pathologic conditions. To help understand TRPM8-mediated cold perception in the dental pulp and periodontal tissues, we examined the distribution of TRPM8-immunopositive (+) axons in molar and incisor pulp and periodontal tissues using transgenic mice expressing a genetically encoded axonal tracer in TRPM8+ neurons. In the radicular pulp of the molar teeth, a small number of TRPM8+ axons were observed. TRPM8+ axons branched frequently and extensively in the core of coronal pulp, forming a network in the peripheral pulp. Some TRPM8+ axons ascended between odontoblasts and were observed in the dentinal tubule. TRPM8+ axons were linear-shaped in the radicular pulp, whereas many TRPM8+ axons showed portions shaped like beads connected with thin axonal stands at the peripheral pulp. TRPM8 was densely expressed in the bead portions. In the incisor pulp, TRPM8+ axons were occasionally observed in the core of the coronal pulp and rarely observed at the peripheral pulp. TRPM8+ axons were occasionally observed and showed a linear shape rather than a bead-like appearance in the periodontal ligament and lamina propria of the gingival tissue. These findings, showing differential distribution of TRPM8+ axons between radicular and coronal portions of the molar pulp, between incisor and molar pulp, and between dental pulp and periodontal tissues, may reflect differential cold sensitivity in these regions.

Temperature as a major environmental factor affects on organisms on various levels including molecular, physiological, behavioral and ecological levels. Transient receptor potential channels (TRPs) are a cation channel family. Among them, thermo-TRPs are known as a thermosensor. The potential role of thermo-TRPs have been identified in the fruit fly, Drosophila melanogaster, in thermotaxis and in thermal acclimation. With RNA interference (RNAi) technique, the role of thermo-TRPs in the red flour beetle, Tribolium castaneum, was identified by measuring thermal avoidance behavior in a behavioral assay. RNAi of trpA1 reduced high temperature avoidance, 39 and 42 °C. Moreover, the effects of RNAi of thermo-TRPs on the heat-induced knockout and the death after short exposure to high temperature was measured after one minute exposure at 52 °C, either with or without a 42 °C 10-minute thermal acclimation period. Even though it was relatively short time exposure to high temperature, it was enough to induce high temperature thermal acclimation. RNAi of trpA1 made faster knockout at 52 °C. With RNAi of painless, the recovery rates from heat-induced knockout after thermal acclimation. RNAi of pyrexia reduced long-term total survivorship without thermal acclimation.

UV 뿐 아니라 가시광선, 적외선에 의해 발생된 열로 인해 피부 온도 상승, MMP-1의 증가에 따른 피부 노화가 진행된다. 따라서 열에 의한 노화에서 피부 온도 조절은 노화 억제에 중요한 핵심 요소이다. 일시적인 수용체 전위 통로인 TRPM8은 멘솔 수용체(CMR1)로써 25 ℃ 이하의 온도에서 활성화되고 시원한 감각을 발생시키는 냉 수용체로 보고되어 있다. TRPM8 조절을 통해 시원한 감각과 피부 온도를 조절하는 연구가 활발히 진행되고 있다. 본 연구에서는 천연물인 영지버섯을 이용하여 냉 수용체인 TRPM8 발현에 어떠한 영향을 주는지 확인하였다. 영지버섯추출물 및 용매 분획물의 TRPM8 발현에 대한 영향을 측정한 결과, 영지버섯추출물, n-hexane 분획물 및 water 분획물에서 농도의존적으로 TRPM8 발현이 증가함을 확인하였 다. Hex 분획물에서 유효성분을 찾고자 크로마토그래피를 실시하여 1개의 화합물을 분리하였으며 1H 및 13C NMR spectrum 분석을 통하여 화학구조를 동정하였다. 분리된 화합물은 에르고스테롤로 TRPM8 발현 증가에 효과가 있음을 확인하였다. 결과를 토대로, 영지버섯추출물 및 에르고스테롤은 화장품 분야에서 새로운 쿨링 소재로서 개발가능성이 있다고 사료된다.