Excitation of Mouse Superficial Dorsal Horn Neurons by Histamine and/or PAR-2 Agonist: Potential Role in Itch

Excitation of Mouse Superficial Dorsal Horn Neurons by Histamine and/or PAR-2 Agonist: Potential Role in Itch
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DOI:
10.1152/jn.00463.2009
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发表时间:
2009-10-01
影响因子:
2.5
通讯作者:
Carstens, E.
Carstens, E.
中科院分区:
医学3区
文献类型:
--
作者:
Akiyama, Tasuku;Carstens, Mirela Iodi;Carstens, E.

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Akiyama T,Carstens MI,Carstens E.组胺和/或PAR-2激动剂对小鼠背角浅层神经元的兴奋:在瘙痒中的潜在作用。神经生理学杂志102:2176-2183,2009。2009年7月22日首次出版;DOI:10.1152/jn.00463.2009。最近的研究表明,组胺和非组胺能性痒存在不同的转导机制和感觉通路。我们研究了与非组胺能瘙痒相关的组胺和一种蛋白水解酶激活受体(PAR)-2激动剂是否能兴奋小鼠背角神经元。用戊巴比妥钠麻醉成年ICR小鼠,在腰背角浅层记录到单个单位。使用皮内注射组胺或PAR-2激动剂SLIGRL-NH2寻找单位活性。分离的单位随后用皮内组胺攻击,然后是SLIGRL-NH_2(每个50微克/毫升L)或相反的顺序,然后是机械刺激、热刺激和致过敏刺激。43个单位分为宽动态范围(62%)、伤害特异型(22%)和机械不敏感型(16%)。20个单位对皮内注射组胺有较长时间(平均10分钟)放电;76%对随后的SLIGRL-NH2有反应,通常更短暂。此外,单位还对有毒的高温(63%)、降温(43%)、外用芥子油(53%)和皮内辣椒素(67%)有反应。另外22个单位对最初皮内注射SLIGRL-NH2有较长时间(平均5分钟)的反应;85%对随后的皮内组胺有反应。他们还对剧热(75%)、芥末油(93%)、辣椒素(63%)和一种降温有反应。大多数浅层背角神经元同时被组胺和PAR-2激动剂兴奋,提示组胺和非组胺介导的瘙痒的通路重叠。由于绝大多数瘙痒反应神经元也对伤害性刺激有反应,瘙痒可能至少部分是由种群编码发出的。
Akiyama T, Carstens MI, Carstens E. Excitation of mouse superficial dorsal horn neurons by histamine and/or PAR-2 agonist: potential role in itch. J Neurophysiol 102: 2176-2183, 2009. First published July 22, 2009; doi: 10.1152/jn.00463.2009. Recent studies have suggested the existence of separate transduction mechanisms and sensory pathways for histamine and nonhistaminergic types of itch. We studied whether histamine and an agonist of the protease-activated receptor (PAR)-2, associated with nonhistaminergic itch, excite murine dorsal horn neurons. Single units were recorded in superficial lumbar dorsal horn of adult ICR mice anesthetized with pentobarbital. Unit activity was searched using a small intradermal hindpaw injection of histamine or the PAR-2 agonist SLIGRL-NH2. Isolated units were subsequently challenged with intradermal histamine followed by SLIGRL-NH2 (each 50 mu g/I mu l) or reverse order, followed by mechanical, thermal, and algogenic stimuli. Forty-three units were classified as wide dynamic range (62%), nociceptive specific (22%), or mechano insensitive (16%). Twenty units gave prolonged (mean, 10 min) discharges to intradermal injection of histamine; 76% responded to subsequent SLIGRL-NH2, often more briefly. Units additionally responded to noxious heat (63%), cooling (43%), topical mustard oil (53%), and intradermal capsaicin (67%). Twenty-two other units gave prolonged (mean, 5 min) responses to initial intradermal injection of SLIGRL-NH2; 85% responded to subsequent intradermal histamine. They also responded to noxious heat (75%), mustard oil (93%), capsaicin (63%), and one to cooling. Most superficial dorsal horn neurons were excited by both histamine and the PAR-2 agonist, suggesting overlapping pathways for histamine-and non-histamine-mediated itch. Because the large majority of pruritogen-responsive neurons also responded to noxious stimuli, itch may be signaled at least partly by a population code.