OPTOGENETIC ANALYSIS OF THE DESCENDING PAIN INHIBITORY SYSTEM VIA 5-HT NEURONS IN THE NUCLEUS RAPHE MAGNUS

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  • 大縫線核セロトニン神経による疼痛抑制の光遺伝学的解析
  • ダイホウセンカク セロトニン シンケイ ニ ヨル トウツウ ヨクセイ ノ ヒカリ イデンガクテキ カイセキ

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Abstract

The descending serotonergic pathways originate from the nucleus raphe magnus （NRM） in the rostroventromedial medulla. These pathways mediate pronociceptive action in addition to antinociceptive action. Pain controlled by manipulating serotonin （5-hydroxytryptamine, 5-HT） neurons has not yet been evaluated in free-moving animals. In the present study, we used optogenetics to examine how the excitation of intrinsic 5-HT neurons in the NRM affects pain thresholds in free-moving mice exposed to intermittent cold stress （ICS group）. The mice （Tph2-tTA::tetO-ChR2[C128S]-EYFP） were anesthetized, and an optical fiber was implanted just above the NRM. After a recovery period of three to five days, the mice in the ICS group were housed at 4℃ for three nights, and exposed to room temperatures alternating between 24℃and 4℃ every 30 minutes for two days, to induce neurodegeneration. Pain was evaluated before and after blue light illumination to optogenetically stimulate 5-HT neurons in the NRM. The von Frey and hot plate tests were performed as mechanical- and thermal-pain tests, respectively. Blue light illumination increased the pain thresholds of mice in the sham ICS and ICS groups in the hot plate test, but did not affect their pain thresholds in the von Frey test. These findings suggest that 5-HT neurons in the NRM mediating the descending pain inhibitory system increased the thermal-nociceptive threshold.

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