徳島大学 教育・研究者情報データベース(EDB)

1. 樋浦 明夫

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2. 中川 弘([徳島大学.病院.診療科.小児歯科])

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(英) Changes in response behaviors to noxious heat and mechanical stimuli after carrageenan-induced inflammation in mice treated with capsaicin 2 or 15 days after birth

(英) The aim of the present study was to investigate thecause of normal response behaviors to noxious heatdespite the marked loss of small neurons in the dorsalroot ganglion (DRG) as a result of neonatal capsaicintreatment. Capsaicin (50 mg/kg) was injectedsubcutaneously (s.c.) into mice on either day P2 orP15; control mice received a vehicle injection. Twentydays after the capsaicin injection, 2% carrageenan (20μL) was injected into the right hind paw of each animal.Twenty-four hours after the carrageenan injection,behavioral tests using noxious heat stimuli (NHS;Hargreaves method) and noxious mechanical stimuli(NMS; von Frey method) were performed using thecontrol and capsaicin-treated mice. Pre-carrageenanmeasurements were used as the baseline values foreach group. After the experiments, the mice wereperfused with a mixture of 4% paraformaldehyde and0.2% picric acid in a 0.1-M phosphate buffer (pH 7.4).The L4 and L5 DRGs were extracted, sectioned usinga cryostat, and immunostained using a TRPV1antibody and reacted with isolectin IB4. The P2capsaicin-injected mice exhibited a marked increase intheir analgesic responses to NHS, compared with boththeir baseline values and the respective control mice.Both the capsaicin-treated and control animalsexhibited significant hyperalgesia in response to NMS.Naturally, the control P15 mice exhibited a shorterresponse time to NHS than their baseline values, whilethe capsaicin-injected P15 mice exhibited increasedalgesia comparable to the baseline values of thecontrol. The capsaicin-injected mice also exhibitedalgesia in response to NMS. The number ofTRPV1-immunoreactive (ir) small neurons decreasedby 90% in the P2 capsaicin-injected mice and 45% inthe P15 capsaicin-injected mice, whereas an increasein IB4-positive neurons was seen in both the P2 andP15 capsaicin-injected mice. In association with thedecrease in larger neurons, the numbers of smallerneurons were increased in both P2 and P15capsaicin-injected mice. TRPV1-ir small neurons areclosely correlated with inflammatory heat painperception, suggesting the enhancement of anunknown acute noxious heat sensor in the presentstudy. The present findings indicate that noxiousmechanical stimuli can be sensed despite thepresence or absence of TRPV1-ir or IB4-positiveneurons.