2005 Fiscal Year Final Research Report Summary
Analysis of peripheral mechanism for cold-induced aggravation of pain in inflammation and nerve injury models
| Project/Area Number |
15390070
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Environmental physiology (including Physical medicine and Nutritional physiology)
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| Research Institution | Nagoya University |
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Principal Investigator |
MIZUMURA Kazue Nagoya Univ., Research Inst.Environ.Med., Prof., 環境医学研究所, 教授 (00109349)
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| Co-Investigator(Kenkyū-buntansha) |
SATO Jun Nagoya Univ., Research Inst.Environ.Med., Associate Prof., 環境医学研究所, 助教授 (00235350)
KOZAKI Yasuko Nagoya Univ., Research Inst.Environ.Med., Assist.Prof., 環境医学研究所, 助手 (20126882)
KATANOSAKA Kimiaki Nagoya Univ., Research Inst.Environ.Med., Assist.Prof., 環境医学研究所, 助手 (50335006)
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| Project Period (FY) |
2003 – 2005
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| Keywords | nociceptor / cold / mechanical hyperalgesia / ATP / muscle C-fiber receptors / noradrenaline / heat response / lengthening contraction |
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| Research Abstract |
To clarify the peripheral mechanism for cold-induced aggravation of pain in inflammation and nerve injury models, following experiments were carried out.
1) We examined cold sensitivity of cultured dorsal root ganglion (DRG) neurons obtained from adjuvant-monoarthritic rats using Ca-imaging technique. The percentage of neurons responding to cold down to 10℃ was about 80% both in normal and inflamed animals. Percentage of neurons sensitive to mustard oil (MO, a TRPA1 agonist) was 56% in inflamed animals, much higher than 20% in normal group. The great majority of neurons sensitive to menthol (MT, a TRPM8 agonist) was also sensitive to MO. The threshold temperature to cooling of MO-sensitive and MT-insensitive neurons was 18.4℃ in inflamed group, higher than 14.0℃ in the normal group.
2) We demonstrated the temperature dependency of acid sensitivity in cultured DRG neurons.
3) Mechanical hyperalgesia in adjuvant-monoarthritic rats was worsened by exposure to cold (15℃).
4) To know the basic mechanism for inflammatory hyperalgesia, we examined effects of ATP on C-fiber receptors. ATP suppressed through P2X receptors the heat response of nociceptors at a low concentration (10μM), while it facilitated the heat response through P2Y receptors at a high concentration (1mM).
5) To clarify the interaction of various inflammatory mediators, we examined effects of bradykinin (BK) and noradrenaline (NA) on single C-fiber receptor activities. BK-induced discharges were enhanced by pretreatment with NA, vice versa. This result suggests that despite of its weak excitatory effect by itself, NA in co-operation with other mediators induces larger effects.
6) We induced muscle mechanical hyperalgesia by lengthening contraction of the dorsi-flexors of the lower hindpaw. We demonstrated that the mechanical sensitivity of muscle C-fiber receptors was increased in this hyperalgesic muscle.
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