Maione S, Oliva P, Marabese I, Palazzo E, Rossi F, Berrino L, Filippelli A
Institute of Pharmacology and Toxicology, Faculty of Medicine and Surgery, The Second University of Naples, Via Costantinopoli 16, 80138, Naples, Italy.
Pain. 2000 Mar;85(1-2):183-9. doi: 10.1016/s0304-3959(99)00269-9.
The role played by periaqueductal gray (PAG) matter metabotropic glutamate receptors (mGluRs) in the modulation of persistent noxious stimulation was investigated in mice. The formalin test was used as a model of persistent pain. Intra-PAG microinjections of (S)-3, 5-DHPG (25 and 50 nmol/mouse) and L-CCG-I (30 and 60 nmol/mouse), agonists of group I and group II mGluRs, respectively, decreased the nociceptive response (-92+/-6% and -89+/-8%, respectively) during the late phase. No change of the early nociceptive phase was observed after (S)-3,5-DHPG or L-CCG-I treatments. These effects were antagonized by a pretreatment with CPCCOEt (40 nmol/mouse) and (2S)-alpha-EGlu (30 nmol/mouse). CPCCOEt is a selective antagonist of group I mGlu receptors, while (2S)-alpha-EGlu is an antagonist of group II. Intra-PAG microinjections of L-SOP (60 and 120 nmol/mouse), a selective agonist of group III mGluRs, induced an increase of the nociceptive response (+95+/-7%) during the late hyperalgesic phase. (R,S)-alpha-M-SOP (70 nmol/mouse), a selective antagonist of group III mGluRs, completely antagonized the L-SOP-induced effect. These results show that PAG mGluRs participate in modulating the late hyperalgesic behaviours induced by formalin. It seems, therefore, possible that group I and group II mGluRs positively modulate PAG antinociceptive descending pathway following a persistent noxious stimulation, while group III mGluRs modulate it negatively.
在小鼠中研究了导水管周围灰质（PAG）代谢型谷氨酸受体（mGluRs）在持续性伤害性刺激调节中的作用。福尔马林试验被用作持续性疼痛的模型。分别向PAG内微量注射I组和II组mGluRs的激动剂（S）-3,5-二羟基苯基甘氨酸（25和50 nmol/小鼠）和L-CCG-I（30和60 nmol/小鼠），可降低后期的伤害性反应（分别为-92±6%和-89±8%）。（S）-3,5-二羟基苯基甘氨酸或L-CCG-I处理后，早期伤害性阶段未观察到变化。这些作用被预先注射CPCCOEt（40 nmol/小鼠）和（2S）-α-EGlu（30 nmol/小鼠）所拮抗。CPCCOEt是I组mGlu受体的选择性拮抗剂，而（2S）-α-EGlu是II组的拮抗剂。向PAG内微量注射III组mGluRs的选择性激动剂L-SOP（60和120 nmol/小鼠），可在后期痛觉过敏阶段诱导伤害性反应增加（+95±7%）。III组mGluRs的选择性拮抗剂（R,S）-α-M-SOP（70 nmol/小鼠）完全拮抗了L-SOP诱导的效应。这些结果表明，PAG mGluRs参与调节福尔马林诱导的后期痛觉过敏行为。因此，似乎在持续性伤害性刺激后，I组和II组mGluRs正向调节PAG抗伤害性下行通路，而III组mGluRs则负向调节该通路。
