Intracolonic Mustard Oil Induces Visceral Pain in Mice by TRPA1-Dependent and -Independent Mechanisms: Role of Tissue Injury and P2X Receptors.
Intracolonic Mustard Oil Induces Visceral Pain in Mice by TRPA1-Dependent and -Independent Mechanisms: Role of Tissue Injury and P2X Receptors.
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殖民地芥菜油通过TRPA1依赖性和非依赖性机制诱导小鼠内脏疼痛：组织损伤的作用和P2X受体。
DOI：
10.3389/fphar.2020.613068
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发表时间：
2020
影响因子：
5.6
通讯作者：
Cobos EJ
中科院分区：
文献类型：
--
作者：
Gonzalez-Cano R;Montilla-García Á;Perazzoli G;Torres JM;Cañizares FJ;Fernández-Segura E;Costigan M;Baeyens JM;Cobos EJ
TRPA 1和嘌呤能P2 X受体都被认为是治疗内脏痛的潜在靶点。我们发现，结肠内给药低剂量芥子油（0.5%），一个众所周知的TRPA 1激动剂，产生伤害性反应和腹壁涉及机械性痛觉过敏，而不诱导明显的组织损伤。通过树脂毒素（RTX）处理和TRPA 1拮抗剂AP 18消融TRPV 1表达神经元（以及随后消融TRPA 1+伤害感受器），消除了伤害性反应和牵涉性痛觉过敏。然而，较高剂量的芥子油（2.5%）损伤结肠上皮细胞，并诱导pERK激活脊髓，这些过程显然是独立的TRPV 1表达神经元消融RTX。这种较高剂量的芥子油诱导伤害性反应和机械性痛觉过敏，其对树脂毒素或AP 18不敏感或仅轻微敏感，但被P2 X拮抗剂TNP-ATP显著降低，已知TNP-ATP抑制由损伤组织释放的ATP诱导的伤害性作用。总之，低剂量的结肠内芥子油以完全依赖于TRPA 1作用的方式诱导内脏痛，而当使用高剂量的这种化学刺激物时，内脏痛变得大多不依赖于TRPA 1激活，但明显地被受损结肠上皮释放的ATP增强。因此，TRPA 1抑制不足以显著降低组织损伤期间的内脏疼痛，而嘌呤能拮抗作用似乎是更有效的策略。
Both TRPA1 and purinergic P2X receptors have been proposed as potential targets for the treatment of visceral pain. We found that the intracolonic administration of a low dose mustard oil (0.5%), a well-known TRPA1 agonist, produced nociceptive responses and abdominal wall referred mechanical hyperalgesia, without inducing apparent tissue damage. Both nociceptive responses and referred hyperalgesia were abolished by the ablation of TRPV1-expressing neurons (and the consequent ablation of TRPA1+ nociceptors) by resiniferatoxin (RTX) treatment, and by the TRPA1 antagonist AP18. However, a higher dose of mustard oil (2.5%) damaged the colonic epithelium and induced pERK activation in the spinal cord, and these processes were clearly independent of TRPV1-expressing neurons ablated by RTX. This higher dose of mustard oil induced nociceptive responses and referred mechanical hyperalgesia which were insensitive or only slightly sensitive to resiniferatoxin or AP18, but were markedly reduced by the P2X antagonist TNP-ATP, which is known to inhibit nociceptive actions induced by ATP released from injured tissues. In conclusion, whereas a low dose of intracolonic mustard oil induces visceral pain in a manner fully dependent on TRPA1 actions, when a high dose of this chemical irritant is used, visceral pain becomes mostly independent of TRPA1 activation but clearly enhanced by ATP purportedly released by the damaged colonic epithelium. Therefore, TRPA1 inhibition is not sufficient to substantially decrease visceral pain during tissue injury, whereas purinergic antagonism appears to be a more effective strategy.
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影响因子：
5.3
作者：
Amaya F;Izumi Y;Matsuda M;Sasaki M
通讯作者：
Sasaki M
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2.5
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