An antagonist of substance P N-terminal fragments, D-substance P(1-7), reveals that both nociceptive and antinociceptive effects are induced by substance P N-terminal activity during noxious chemical stimulation
An antagonist of substance P N-terminal fragments, D-substance P(1-7), reveals that both nociceptive and antinociceptive effects are induced by substance P N-terminal activity during noxious chemical stimulation
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DOI：
10.1016/s0006-8993(97)01146-3
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发表时间：
1998-01-05
期刊：
影响因子：
2.9
通讯作者：
Larson, AA
中科院分区：
文献类型：
--
作者：
Goettl, VM;Larson, AA
已知P物质（SP） n端片段在鞘内注射或在辣椒素作用下释放时可改变痛觉。然而，尚不清楚在有害刺激过程中是否有足够浓度的SP n端代谢物积累来调节伤害感受。为了避免这种情况，我们研究了SP（1-7）拮抗剂D-SP（1-7）在小鼠鞘内注射对两种不同外源性SP（1-7）影响的伤害性实验的影响：醋酸诱导的扭曲被抑制，福尔马林诱导的行为被SP（1-7）增强。1 nmol的D-SP（1-7）足以阻断SP（1-7）对扭体的急性（30min）抗伤感受作用。当以高剂量（10-100 nmol）单独注射时，D-SP（1-7）抑制扭动。在福尔马林试验中，SP（1-7）在任何剂量下对第一阶段的反应都没有急性影响（30分钟），但D-SP（1-7）在注射低剂量（2-1000 pmol）后5分钟增加了反应，但没有高剂量（10和100 nmol）。注射SP(1-7) 24 h后，扭体受到抑制，福尔马林反应增强。D-SP（1-7）阻止了SP（1-7）的这些作用，但单独注射时没有作用，这表明未暴露于有害刺激的小鼠没有补性SP n端活性。因此，乙酸和福尔马林分别诱导内源性SP n端活性，产生对D-SP相对不敏感的促伤害作用（1-7）和对D-SP抑制非常敏感的抗伤害作用（1-7）。(C) 1998爱思唯尔科学有限公司
Substance P (SP) N-terminal fragments are known to alter nociception when injected intrathecally or when released in response to capsaicin. However, it is not known whether a sufficient concentration of SP N-terminal metabolites accumulate during noxious stimulation to modulate nociception. To lest this, we examined the effect of the SP(1-7) antagonist, D-SP(1-7), injected intrathecally in mice, on two nociceptive assays that are differentially affected by exogenous SP(1-7): acetic acid-induced writhing that is inhibited and formalin-induced behaviors that are enhanced by SP(1-7). One nmol of D-SP(1-7) is sufficient to block the acute (30 min) antinociceptive effects of SP(1-7) on writhing. When injected alone at much higher doses (10-100 nmol), D-SP(1-7) inhibited writhing. In the formalin assay, SP(1-7) had no acute effect (30 min) on responses during Phase 1 at any dose tested, but D-SP(1-7) increased responses 5 min after injection of low (2-1000 pmol), but not high doses (10 and 100 nmol). Twenty-four hours after injection of SP(1-7), writhing was inhibited and formalin responses were increased. D-SP(1-7) prevented these effects of SP(1-7) but had no effect when injected alone, indicating that there is no tonic SP N-terminal activity in mice not exposed to noxious stimuli. Thus, acetic acid and formalin each induce endogenous SP N-terminal activity, respectively, producing a pro-nociceptive effect that is relatively insensitive to D-SP(1-7) and antinociception that is very sensitive to inhibition by D-SP(1-7). (C) 1998 Elsevier Science B.V.