Evidence for the involvement of spinal endogenous ATP and P2X receptors in nociceptive responses caused by formalin and capsaicin in mice
Evidence for the involvement of spinal endogenous ATP and P2X receptors in nociceptive responses caused by formalin and capsaicin in mice
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DOI：
10.1038/sj.bjp.0702960
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发表时间：
1999-12-01
影响因子：
7.3
通讯作者：
Inoue, K
中科院分区：
文献类型：
--
作者：
Tsuda, M;Ueno, S;Inoue, K
1本研究的目的是探讨脊髓内源性ATP和P2 X受体在神经源性疼痛和炎性疼痛中的作用。我们研究了鞘内注射P2 X受体拮抗剂对福尔马林和辣椒素诱导的小鼠伤害性行为的影响。2鞘内注射一般P2受体拮抗剂磷酸吡哆醛-6-偶氮苯基-2 '，4'-二磺酸（PPADS）预处理，可显著抑制福尔马林诱导的伤害性行为的第一和第二阶段。第二阶段的伤害性反应也被抑制鞘内治疗PPADS后的第一阶段。此外，还用P2 X（1）、P2 X（3）和P2 X（2+3）受体的选择性拮抗剂2 ′，3 ′-O-（2，4，6-三硝基苯基）腺苷5 ′-三磷酸（TNP-ATP）预处理。第一个阶段明显减少，但第二个阶段没有减少。鞘内注射TNP-ATP后，第二时相也没有受到抑制。3辣椒素诱导的伤害性行为已被证明是神经源性疼痛的模型，也被鞘内注射PPADS或TNP-ATP显著抑制。4福尔马林试验和辣椒素试验第一时相的伤害性行为被鞘内注射α，β-亚甲基ATP显著抑制（α，β meATP：5 μ g小鼠（-1）），注射福尔马林或辣椒素前15分钟。这种治疗之前已经在小鼠体内显示出脊髓P2 X（3）受体亚型脱敏。5这些发现表明脊髓内源性ATP可能在（1）福尔马林和辣椒素诱导的神经源性疼痛中起作用，通过PPADS和TNP-ATP敏感的P2 X受体，β-meATP（可能是P2 X（3）受体亚型）和（2）福尔马林通过PPDS敏感性、TNP-ATP和α，β-meATP不敏感性P2 X（和/或P2 Y）受体诱导的炎性疼痛。
1 The aim of the present study is to characterize the role of spinal endogenous ATP and P2X receptors in the generation of neurogenic and inflammatory pain. We examined the effects of intrathecal treatment with P2X receptor antagonists on the formalin- and capsaicin-induced nociceptive behaviours in mice.2 Intrathecal pretreatment with the general P2 receptor antagonist, pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS), significantly suppressed both the first and second phases of the formalin-induced nociceptive behaviour. The second phase of the nociceptive response was also suppressed by intrathecal treatment with PPADS after the first phase. Furthermore, pretreatment with the selective antagonist for the P2X(1), P2X(3) and P2X(2+3); receptors, 2',3'-O-(2,4,6-trinitrophenyl)adenosine 5'-triphosphate (TNP-ATP). significantly reduced the first phase, but not the second phase. The second phase was also not suppressed by intrathecal TNP-ATP after the first phase.3 Capsaicin-induced nociceptive behaviour that has been shown to be a model for neurogenic pain, was also significantly suppressed by intrathecal pretreatment with PPADS or TNP-ATP.4 Nociceptive behaviour in the first phase of the formalin test and in the capsaicin test were significantly inhibited by intrathecal pretreatment with alpha,beta-methylene ATP (alpha,beta meATP: 5 mu g mouse(-1)) 15 min prior to injection of formalin or capsaicin. This treatment has been previously mouse shown to desensitize spinal P2X(3) receptor subtypes in vivo.5 These findings suggest that spinal endogenous ATP may play a role in (1) the formalin- and capsaicin-induced neurogenic pain via the PPADS- and TNP-ATP-sensitive P2X receptors which are also desensitized by alpha,beta meATP (perhaps the P2X(3) receptor subtype) and (2) formalin-induced inflammatory pain via PPADS-sensitive, TNP-ATP- and alpha,beta meATP-insensitive P2X (and/or P2Y) receptors.