Peripheral effects of morphine and expression of μ-opioid receptors in the dorsal root ganglia during neuropathic pain: nitric oxide signaling.
Peripheral effects of morphine and expression of μ-opioid receptors in the dorsal root ganglia during neuropathic pain: nitric oxide signaling.
复制标题
DOI：
10.1186/1744-8069-7-25
复制
发表时间：
2011-04-12
期刊：
影响因子：
3.3
通讯作者：
Pol O
中科院分区：
文献类型：
--
作者：
Hervera A;Negrete R;Leánez S;Martín-Campos JM;Pol O
μ-阿片受体（莫尔）激动剂的局部给药可减轻神经病理性疼痛，但这种作用涉及的确切机制尚未完全阐明。本研究旨在探讨神经型和诱导型一氧化氮合酶（NOS 1和NOS 2）合成的一氧化氮是否能通过激活外周一氧化氮-cGMP-蛋白激酶G（PKG）-ATP敏感性K+（KATP）通道信号通路调节吗啡的局部抗痛觉超敏作用，并影响背根神经节莫尔的表达。在野生型（WT）小鼠中，足底给药吗啡剂量依赖性地降低了由坐骨神经慢性收缩（CCI）诱导的机械和热异常性疼痛，在与不同亚镇痛剂量的选择性NOS 1（N-[（4S）-4-氨基-5-[（2-氨乙基）氨基]戊基]-N '-硝基胍三（三氟乙酸）盐; NANT），NOS 2（L-N（6）-（1-亚氨基乙基）-赖氨酸，L-鸟苷酸环化酶（1H-[1，2，4]恶二唑并[4，3-a]喹喔啉-1-酮; ODQ），PKG（（Rp）-8-（对氯苯硫基）鸟苷-3 '，5'-环状单硫代磷酸酯; Rp-8-pCPT-cGMP）抑制剂或KATP通道阻断剂（格列本脲）。在手术后21天，对来自假手术和坐骨神经损伤的WT、NOS 1敲除（KO）和NOS 2-KO小鼠的背根神经节中的莫尔表达的评价表明，尽管WT和两种NOS-KO动物之间的莫尔的基础mRNA和蛋白水平相似，但神经损伤仅降低了WT小鼠中的MOR表达。这些结果表明，外周NO-cGMP-PKG-KATP信号通路的激活参与了坐骨神经损伤后吗啡的局部抗异常性疼痛作用，NOS 1和NOS 2合成的NO参与了神经病理性疼痛时背根神经节对莫尔的下调。
The local administration of μ-opioid receptor (MOR) agonists attenuates neuropathic pain but the precise mechanism implicated in this effect is not completely elucidated. We investigated if nitric oxide synthesized by neuronal (NOS1) or inducible (NOS2) nitric oxide synthases could modulate the local antiallodynic effects of morphine through the peripheral nitric oxide-cGMP-protein kinase G (PKG)-ATP-sensitive K+ (KATP) channels signaling pathway activation and affect the dorsal root ganglia MOR expression during neuropathic pain. In wild type (WT) mice, the subplantar administration of morphine dose-dependently decreased the mechanical and thermal allodynia induced by the chronic constriction of the sciatic nerve (CCI), which effects were significantly diminished after their co-administration with different subanalgesic doses of a selective NOS1 (N-[(4S)-4-amino-5-[(2-aminoethyl)amino]pentyl]-N'-nitroguanidine tris(trifluoroacetate) salt; NANT), NOS2 (L-N(6)-(1-iminoethyl)-lysine; L-NIL), L-guanylate cyclase (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one; ODQ), PKG ((Rp)-8-(para-chlorophenylthio)guanosine-3',5'-cyclic monophosphorothioate; Rp-8-pCPT-cGMPs) inhibitor or a KATP channel blocker (glibenclamide). The evaluation of the expression of MOR in the dorsal root ganglia from sham-operated and sciatic nerve-injured WT, NOS1 knockout (KO) and NOS2-KO mice at 21 days after surgery demonstrated that, although the basal mRNA and protein levels of MOR were similar between WT and both NOS-KO animals, nerve injury only decreased their expression in WT mice. These results suggest that the peripheral nitric oxide-cGMP-PKG-KATP signaling pathway activation participates in the local antiallodynic effects of morphine after sciatic nerve injury and that nitric oxide, synthesized by NOS1 and NOS2, is implicated in the dorsal root ganglia down-regulation of MOR during neuropathic pain.
登录
查看更多内容
影响因子：
7.4
作者：
Obara, Ilona;Parkitna, Jan Rodriguez;Przewlocki, Ryszard
通讯作者：
Przewlocki, Ryszard
影响因子：
7.4
作者：
Guan, Yun;Johanek, Lisa M.;Raja, Srinivasa N.
通讯作者：
Raja, Srinivasa N.
DOI：
10.1124/jpet.110.167585
发表时间：
2010-09-01
影响因子：
3.5
作者：
Hervera, Arnau;Negrete, Roger;Pol, Olga
通讯作者：
Pol, Olga
影响因子：
4.7
作者：
Pol, O;Murtra, P;Maldonado, R
通讯作者：
Maldonado, R
影响因子：
3.3
作者：
Zoga V;Kawano T;Liang MY;Bienengraeber M;Weihrauch D;McCallum B;Gemes G;Hogan Q;Sarantopoulos C
通讯作者：
Sarantopoulos C