Evidence for the modulation of nociception in mice by central mast cells.

Evidence for the modulation of nociception in mice by central mast cells.
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DOI:
10.1002/ejp.1086
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发表时间:
2017-11
期刊:
European journal of pain (London, England)
影响因子:
--
通讯作者:
Larson AA
Larson AA
中科院分区:
其他
文献类型:
--
作者:
Kissel CL;Kovács KJ;Larson AA

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Hyperalgesia that develops following nerve ligation corresponds temporally and in magnitude with the number of thalamic mast cells located contralateral to the ligature. We tested the possibility that mast cells modulate nociception centrally, similar to their role in the periphery. We examined the central effect of two hyperalgesic compounds that also induce mast cell degranulation and stabilized mast cells using cromolyn. Thermal hyperalgesia (tail flick) induced by nerve growth factor (NGF, a neurotrophic compound) and mechanical hyperalgesia (von Frey) induced by dynorphin A (1–17) (opioid compound) each correlated with the percent of thalamic mast cells that were degranulated. Degranulation of these mast cells by the central injection of compound 48/80, devoid of neurotrophic or opioid activity, was sufficient to recapitulate thermal hyperalgesia. Stabilization of mast cells by central injections of cromolyn produced no analgesic effect on baseline tail flick or von Frey fiber sensitivity, but inhibited thermal hyperalgesia produced by compound 48/80 and tactile hyperalgesia induced by dynorphin and by Freund’s complete adjuvant. Finally, chemical nociception produced by the direct activation of nociceptors by formalin (phase I) was not inhibited by centrally injected cromolyn whereas chemical nociception dependent on central sensitization (formalin-phase II and acetic acid-induced abdominal stretches) was. These convergent lines of evidence suggest that degranulation of centrally located mast cells sensitizes central nociceptive pathways leading to hyperalgesia and tonic chemical sensitivity.
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