کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
6272028 1614776 2015 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Sensory neuron subpopulation-specific dysregulation of intracellular calcium in a rat model of chemotherapy-induced peripheral neuropathy
ترجمه فارسی عنوان
اختلال در تنظیم غلظت کلسیم داخل سلولی در یک مدل موش مبتلا به نوروپاتی محیطی ناشی از شیمیدرمانی
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب (عمومی)
چکیده انگلیسی


- Paclitaxel-induced mechanical hypersensitivity is specific to the glabrous skin.
- Paclitaxel-induced Ca2+ dysregulation is sensory neuron subpopulation-specific.
- The largest paclitaxel-induced changes occur in glabrous skin putative nociceptors.
- Mechanisms underlying these changes may suggest therapeutic targets for CIPN.

The purpose of the present study was to test the prediction that the unique manifestation of chemotherapeutic-induced peripheral neuropathy (CIPN) would be reflected in a specific pattern of changes in the regulation of the intracellular Ca2+ concentration ([Ca2+]i) in subpopulations of cutaneous neurons. To test this prediction, we characterized the pattern of changes in mechanical nociceptive threshold associated with paclitaxel administration (2 mg/kg, iv, every other day for four days), as well as the impact of target of innervation and paclitaxel treatment on the regulation of [Ca2+]i in subpopulations of putative nociceptive and non-nociceptive neurons. Neurons innervating the glabrous and hairy skin of the hindpaw as well as the thigh were identified with retrograde tracers, and fura-2 was used to assess changes in [Ca2+]i. Paclitaxel was associated with a persistent decrease in mechanical nociceptive threshold in response to stimuli applied to the glabrous skin of the hindpaw, but not the hairy skin of the hindpaw or the thigh. However, in both putative nociceptive and non-nociceptive neurons, resting [Ca2+]i was significantly lower in neurons innervating the thigh after treatment. The magnitude of the depolarization-evoked Ca2+ transient was also lower in putative non-nociceptive thigh neurons. More interestingly, while paclitaxel had no detectable influence on either resting or depolarization-evoked Ca2+ transients in putative non-nociceptive neurons, in putative nociceptive neurons there was a subpopulation-specific decrease in the duration of the evoked Ca2+ transient that was largely restricted to neurons innervating the glabrous skin. These results suggest that peripheral nerve length alone, does not account for the selective distribution of CIPN symptoms. Rather, they suggest the symptoms of CIPN reflect an interaction between the toxic actions of the therapeutic and unique properties of the neurons deleteriously impacted.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuroscience - Volume 300, 6 August 2015, Pages 210-218
نویسندگان
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