| Budget Amount *help |
¥15,000,000 (Direct Cost: ¥15,000,000)
Fiscal Year 2005: ¥7,200,000 (Direct Cost: ¥7,200,000)
Fiscal Year 2004: ¥7,800,000 (Direct Cost: ¥7,800,000)
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| Research Abstract |
In animal, heat stimulation is transmitted to central nervous system (CNS) via sensory neuron, and is recognized as heat or pain. Various levels of heat sensations activate the multi functional pain receptors, TRPV channels that expressed in sensory ganglia. Many behavioral tests had been established to measure the pain sensitivity in rodents by investigating behavioral response from the aversive pain stimuli. Hot plate test displays the ability of pain recognition system or analgesic system based on upper CNS. The tail flick test displays the pain sensitivity based on nociceptive reflex. In the present study, we conducted QTL analyses to characterize genetic loci involved in the different sensitivity to heat evoked pain between two mouse strains, C57BL/6 and KJR. In the study, we applied hot plate test and tail flick test to assess the two types of pain sensitivity of BKF2 progeny generated form F1 progeny of C57BL/6 and KJR. In the analyses, we detected three significant loci for hot
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plate test, Hpq1, Hpq2 and Hpq3 and two significant loci for tail flick test, Tfq1 and Tfq2. The pain associated quantitative traits loci, Hpq1, Hpq2, Hpq3, Tfq1, and Tfq2 were located on the chromosomes, 2,10,18,8 and 10, respectively. Hpq2 and Tfq1 were overlapped on the same region of chromosome 10. These data suggested that genetic mechanism for strain difference of pain sensitivities between C57BL/6 and KJR that mediated by upper CNS and reflection system are mostly different but partly shared.
To elucidate phenotype of thermo-sensation, we conducted recording of femoral nerve activity in vivo and intracellular free calcium (iCa) response to heat in vitro in mice of KJR. KJR is the mice strain known to be resistant to hot-plate test. Increment in neuronal activity from 25 C to 40 C was not different in KJR compared to the control. Whereas that from 25 C to 50 C was was different in KJR, when the degree of the increment was compared with C57BL/6 by two-way ANOVA. DRG neurons were isolated from these mice and iCa was measured by ratio methods with fluo-3 and fura-red. Surprisingly, all of the phenotypes including capsaicin resistance in KJR are not reproduced in isolated DRG neurons : We observed rise in iCa in some DRG neurons of KJR to heat and capsaicin. These results may suggest that thermo-sensation is a complicated sensory process involving contribution of proteins other than TRP channels and that the experiments in vitro and in vivo are needed to substantiate the phenotype. Less
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