鞘内靶向沉默5-HT_（5A）受体基因对化疗痛的影响
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摘要
目的:观察鞘内注射5-HT5AR的小干扰RNA重组腺病毒载体(Ad-5-HT5A-siRNA)前后,化疗痛大鼠脊髓5-HT5AR表达和痛觉过敏的变化情况,探讨5-HT5AR在化疗痛中的作用。
方法:第一部分雄性成年SD大鼠随机分为模型组(n=10)和对照组(n=10),模型组腹腔注射长春新碱,对照组腹腔注射生理盐水,定期测定大鼠的机械痛阈及RT-PCR检测建模结束时大鼠脊髓L4-5段5-HT5AR的mRNA表达。第二部分30只已成功建立化疗痛模型大鼠随机分为三组(n=10),实验组鞘内注射Ad-5-HT5A-siRNA,阴性对照组鞘内注射阴性对照腺病毒(Ad-X-HK),空白对照组鞘内注射生理盐水。鞘内注射后3、7d检测各组L4-5脊髓5-HT5AR的表达,并分别在鞘内注射前及注射后3、5、7d测定机械痛阈。
结果:腹腔注射长春新碱可引起模型组大鼠机械痛阈下降(P<0.01)和脊髓5-HT5AR的mRNA表达增高。而鞘内注射后7d,实验组大鼠5-HT5AR的mRNA表达下降,同时该组大鼠的机械痛阈降低(与阴性对照组、空白对照组比较,P<0.05)。
结论: 5-HT5AR参与了化疗痛的调控过程,其表达增强时可能有减轻化疗痛的作用。
Objective: To investigate the role of 5-HT5A receptors in rats with chemotherapy-evoked hyperalgesia by intrathecal injection of adenovirus-mediated small-interference RNA.
Methods: Adult male SD rats were randomly divided into 2 groups: model group (n=10, intraperitoneal injection of vincristine) and control group (n=10, intraperitoneal injection of normal saline). The mechanical hyperalgesia were measured as the paw withdrawal thresholds(PWT) and the expression of 5-HT5AR mRNA in L4-5 spinal cord were determined by RT-PCR. Thirty rats with chemotherapy-evoked hyperalgesia were randomly divided into 3 groups after the formation of chemotherapy pain model: experimental group, negative control group and blank control group, which respectively were treated with intrathecal injection of Ad-5-HT5AR-siRNA, Ad-X-HK and normal saline. Expressions of 5-HT5AR mRNA and PWT after intrathecal injection were assessed respectively.
Results: Compared with control group, PWT of rats in model group were significantly decreased (P<0.01), and levels of 5-HT5AR mRNA were increased. But after intrathecal injection, expressions of 5-HT5AR were down-regulated in experimental group. Meanwhile, PWT of rats in experimental group were lower than those in negative control group and blank control group (P<0.05).
Conclusions: 5-HT5AR is involved in the mechanism of chemotherapy-evoked hyperalgesia and may has antinociceptive effect.
方法:第一部分雄性成年SD大鼠随机分为模型组(n=10)和对照组(n=10),模型组腹腔注射长春新碱,对照组腹腔注射生理盐水,定期测定大鼠的机械痛阈及RT-PCR检测建模结束时大鼠脊髓L4-5段5-HT5AR的mRNA表达。第二部分30只已成功建立化疗痛模型大鼠随机分为三组(n=10),实验组鞘内注射Ad-5-HT5A-siRNA,阴性对照组鞘内注射阴性对照腺病毒(Ad-X-HK),空白对照组鞘内注射生理盐水。鞘内注射后3、7d检测各组L4-5脊髓5-HT5AR的表达,并分别在鞘内注射前及注射后3、5、7d测定机械痛阈。
结果:腹腔注射长春新碱可引起模型组大鼠机械痛阈下降(P<0.01)和脊髓5-HT5AR的mRNA表达增高。而鞘内注射后7d,实验组大鼠5-HT5AR的mRNA表达下降,同时该组大鼠的机械痛阈降低(与阴性对照组、空白对照组比较,P<0.05)。
结论: 5-HT5AR参与了化疗痛的调控过程,其表达增强时可能有减轻化疗痛的作用。
Objective: To investigate the role of 5-HT5A receptors in rats with chemotherapy-evoked hyperalgesia by intrathecal injection of adenovirus-mediated small-interference RNA.
Methods: Adult male SD rats were randomly divided into 2 groups: model group (n=10, intraperitoneal injection of vincristine) and control group (n=10, intraperitoneal injection of normal saline). The mechanical hyperalgesia were measured as the paw withdrawal thresholds(PWT) and the expression of 5-HT5AR mRNA in L4-5 spinal cord were determined by RT-PCR. Thirty rats with chemotherapy-evoked hyperalgesia were randomly divided into 3 groups after the formation of chemotherapy pain model: experimental group, negative control group and blank control group, which respectively were treated with intrathecal injection of Ad-5-HT5AR-siRNA, Ad-X-HK and normal saline. Expressions of 5-HT5AR mRNA and PWT after intrathecal injection were assessed respectively.
Results: Compared with control group, PWT of rats in model group were significantly decreased (P<0.01), and levels of 5-HT5AR mRNA were increased. But after intrathecal injection, expressions of 5-HT5AR were down-regulated in experimental group. Meanwhile, PWT of rats in experimental group were lower than those in negative control group and blank control group (P<0.05).
Conclusions: 5-HT5AR is involved in the mechanism of chemotherapy-evoked hyperalgesia and may has antinociceptive effect.
引文
[1]Cella D, Peterman A, Hudgens S, et al. Measuring the side effects of taxane therapy in oncology: the functional assessment of cancer therapy-taxane (FACT-taxane)[J]. Cancer, 2003, 98(4): 822-831.
[2] Xiao W, Boroujerdi A, Bennett GJ,et al. Chemotherapy-evoked painful peripheral neuropathy: analgesic effects of gabapentin and effects on expression of thealpha-2-delta type-1 calcium channel subunit.[J]. Neuroscience. 2007, 144(2):714-20.[3]
[3]Jorgensen HS. Studies on the neuroendocrine role of serotonin[J].Dan Med Bull.2007,54(4):266-288
[4] Francis C. Colpaert, Kristof Deseure. High-Efficacy 5-Hydroxytryptamine 1A Receptor Activation Counteracts Opioid Hyperallodynia and Affective Conditioning[J]' Pharmacol Exp Ther.2006, 316:892–899
[5] Obata H,Saito S,Sasaki M,et al. Antiallodynic effect of intrathecally administered 5-HT(2) agonists in rats with nerve ligation[J]. Pain, 2001, 90(1-2):73-179
[6] Karla P. Zeitz, Nicolas Guy, Annika B. Malmberg The 5-HT3 Subtype of Serotonin Receptor Contributes to Nociceptive Processing via a Novel Subset of Myelinated and Unmyelinated Nociceptors Journal Neuroscience, February 1, 2002, 22(3):1010-1019
[7] García-Alcocer G,Sarabia-Altamirano G, Martínez-Torres A,et al. Developmental expression of 5-HT 5A receptor mRNA in the rat brain[J]. Neurosci Lett, 2005; 379(2):101-105.
[8]陈晶,周亮,王亚云,等.坐骨神经分支选择性损伤模型大鼠脊髓背角内5-羟色胺4-7受体亚型mRNAs的表达变化[J].中国临床康复,2006;10(32):95-98.
[9] Wu S, Zhu M, Wang W, et al .Changes of the expression of 5-HT receptor subtype mRNAs in rat dorsal root ganglion by complete Freund's adjuvant-induced inflammation. Neurosci Lett, 2001, 20,307(3):183-186
[1] Chen JJ, Vasko MR,Wu X, et al. Multiple subtypes of serotonin receptors are expressed in rat sensory neurons in culture[J]. Pharmacol Exp Ther, 1998;287(3):1119-1127.
[2] Ohta T, Ikemi Y, Murakami M, et al. Potentiation of transient receptor potential V1functions by the activation of metabotropic 5-HT receptors in rat primary sensory neurons[J]. Physiol, 2006; 576(3):809-822.
[3]陈治军,田玉科,罗放.紫杉醇致大鼠外周NPP模型的建立[J]华中科技大学学报(医学版),2008, 37(6):785-790.
[4]Siau C, Xiao W, Bennett GJ. Paclitaxel- and vincristine-evoked painful peripheral neuropathies: loss of epidermal innervation and activation of Langerhans cells[J].Exp Neurol. 2006 ,201(2):507-514.
[5] Nishida K, Kuchiiwa S, Oiso S, et al. Up-regulation of matrix metalloproteinase-3 in the dorsal root ganglion of rats with paclitaxel-induced neuropathy[J].Cancer Sci.2008, 99(8):1618-1625.
[6] Peters CM, Jimenez-Andrade JM,Jonas BM,et al Intravenous paclitaxel administration in the rat induces a peripheral sensory neuropathy characterized by macrophage infiltration and injury to sensory neurons and their supporting cells[J]. Exp Neurol,2007,203(1):42-54.
[7]Xiao WH, Bennett GJ. Chemotherapy-evoked neuropathic pain: Abnormal spontaneous discharge in A-fiber and C-fiber primary afferent neurons and its suppression by acetyl-L-carnitine[J]. Pain.2008,135(3):262-270.
[8]Weng HR, Cordella JV, Dougherty PM.Changes in sensory processing in the spinal dorsal horn accompany vincristine-induced hyperalgesia and allodynia. [J].Pain.2003,103(1-2):131-8
[9]Xiao W, Boroujerdi A, Bennett GJ,et al. Chemotherapy-evoked painful peripheral neuropathy: analgesic effects of gabapentin and effects on expression of the alpha-2-delta type-1 calcium channel subunit.[J]. Neuroscience. 2007,144(2):714-20.
[10]李大鹏,于世英.长春新碱致神经病理性疼痛模型中胶质细胞及IL-1β、GDNF表达的变化[J].肿瘤防治研究,2007,34(2):93-95
[11]Weng HR, Cordella JV, Dougherty PM. Changes in sensory processing in the spinal dorsal horn accompany vincristine-induced hyperalgesia and allodynia[J].Pain, 2003, 103(1-2):131-138.
[12]Aley KO,Reichling DB,Levine JD. Vincristine hyperalgesia in the rat: a model of painful vincristine neuropathy in humans [J]. Neuroscience, 1996; 73(1):259-265.
[1]Natt F. siRNAs in drug discovery: target validation and beyond[J].Curr Opin Mol Ther,2007;9(3):242-7
[2]Naqvi AR, Islam MN, Choudhury NR, Haq QM. The fascinating world of RNA interference[J]. Int J Biol Sci. 2009,5(2):97-117.
[3]Amarzguioui M, Rossi JJ, Kim D. Approaches for chemically synthesized siRNA and vector-mediated RNAi[J]. FEBS Lett. 2005, 579(26):5974-5981.
[4]Vorburger SA, Hunt KK. Adenoviral gene therapy[J]. Oncologiest, 2002;7(1):46-59
[5]Huang B,Schiefer J,Sass C,et al. High-capacity adenoviral vector-mediated reduction of huntingtin aggregate load in vitro and in vivo[J]. Hum Gene Ther, 2007;18(4):303-311.
[6]Chen Y, Chen H, Hoffmann A,et al. Adenovirus-mediated small-Interference RNA for in vivo silencing of angiotensin AT1a receptors in mouse brain[J]. Hypertension,2006;47(2);230-237.
[7]Matthews DA, Cummings D, Evelegh C, et al. Development and use of a 293 cell line expressing lac repressor for the rescue of recombinant adenoviruses expressing high levels of rabies virus glycoprotein[J]. Gen Virol. 1999,80(pt2):345-353.
[8]Milligan ED, Hinde JL, Mehmert KK, et al. A method for increasing the viability of the external portion of lumbar catheters placed in the spinal subarachnoid space of rats[J]. Neurosci Methods,1999;90(1):8l-86
[9]Noda M, Yasuda S, Okada M, et al. Recombinant human serotonin 5A receptors stably expressed in C6 glioma cells couple to multiple signal transduction pathways[J]. Neurochem. 2003;84(2):222-232
[1] Cella D,Peterman A, Hudgens S, et al. Measuring the side effects of taxane therapy in oncology: the functional assessment of cancer therapy-taxane (FACT-taxane).[J].Cancer, 2003, 98(4): 822-831.
[2] Singhal M, Bakhshi S.Primary myositis coinciding with vincristine-induced neuropathic pain and urinary retention in rhabdomyosarcoma: an unusual occurrence.[J]. Pediatr Hematol Oncol,2008, 30(11):869.
[3]] Marcus AI, Peters U, Thomas SL,et al. Mitotic kinesin inhibitors induce mitotic arrest and cell death in Taxol-resistant and -sensitive cancer cells. [J]Biol Chem.2005,280(12):11569-11577.
[4] Joseph EK, Levine JD. Comparison of oxaliplatin- and cisplatin-induced painful peripheral neuropathy in the rat [J]. Pain, 2009,10(5):534-541.
[5]Park SB, Krishnan AV,Lin CS, et al. Mechanisms underlying chemotherapy-induced neurotoxicity and the potenetial for neuroprotective strategies[J].Curr Med Chem.2008, 15(29):3081-3094.
[6] Durie V, Mc Carson KE. Persistent Pain produces stress like alterations in hippocampal neurogenesis and gene expression.[J]. Pain, 2006, 7(8):544-555..
[7]陈治军,田玉科,罗放.紫杉醇致大鼠外周NPP模型的建立[J]华中科技大学学报(医学版),2008, 37(6):785-790.
[8]Siau C, Xiao W, Bennett GJ. Paclitaxel- and vincristine-evoked painful peripheral neuropathies: loss of epidermal innervation and activation of Langerhans cells[J].Exp Neurol. 2006 ,201(2):507-514.
[9] Topp KS, Tanner KD, Levine JD. Damage to the cytoskeleton of large diametersensory neurons and myelinated axons in vincristine-induced painful peripheral neuropathy in the rat[J].Comp Neurol. 2000, 424(4):563-576.
[10]Xiao WH, Bennett GJ. Chemotherapy-evoked neuropathic pain: Abnormal spontaneous discharge in A-fiber and C-fiber primary afferent neurons and its suppression by acetyl-L-carnitine[J]. Pain.2008,135(3):262-270.
[11]Chung JM,Chung K. Sodium channels and neuropathic pain[J]. Novartis Found Symp, 2004, 261:19-27.
[12]Nieto FR, Entrena JM, Cendan CM, et a1. Tetrodotoxin inhibits the development and expression of neurepathic pain induced by paclitaxel in mice[J]. Pain.,2008,137(3):520-531.
[13]Oh SB,Tran PB,Gillard SE, et a1. Chemokines and glycoprotein 120 produce pain hypersensitivity by directly exciting primary nociceptive neurons[J]. Neurosci,2001,21(14): 5027-5035.
[14] Nishida K, Kuchiiwa S, Oiso S, et al. Up-regulation of matrix metalloproteinase-3 in the dorsal root ganglion of rats with paclitaxel-induced neuropathy[J].Cancer Sci.2008, 99(8):1618-1625.
[15] Peters CM, Jimenez-Andrade JM,Jonas BM,et al Intravenous paclitaxel administration in the rat induces a peripheral sensory neuropathy characterized by macrophage infiltration and injury to sensory neurons and their supporting cells[J]. Exp Neurol,2007,203(1):42-54.
[16] Chizh BA,O'Donnell MB,Napolitano A,et al. The effects of the TRPV1 antagonist SB-705498 on TRPV1 receptor-mediated activity and inflammatory hyperalgesia in humans[J].Pain.2007 ,132(1-2):132-41.
[17] Ta LE, Bieber AJ, Carlton SM, et al.Transient Receptor Potential Vanilloid 1 is essential for cisplatin-induced heat hyperalgesia in mice[J].Mol Pain. 2010 ,6(1):15.
[18] Weng HR, Cordella JV, Dougherty PM.Changes in sensory processing in the spinal dorsal horn accompany vincristine-induced hyperalgesia and allodynia. [J].Pain.2003,103(1-2):131-8
[19] Cata JP, Weng HR, Chen JH,et al. Altered discharges of spinal wide dynamic rangeneurons and down-regulation of glutamate transporter expression in rats with paclitaxel-induced hyperalgesia[J]. Neuroscience. 2006,138(1):329-38.
[20] Xiao W, Boroujerdi A, Bennett GJ,et al. Chemotherapy-evoked painful peripheral neuropathy: analgesic effects of gabapentin and effects on expression of the alpha-2-delta type-1 calcium channel subunit.[J]. Neuroscience. 2007,144(2):714-20.
[21] Hald A. Spinal astrogliosis in pain models: cause and effects[J].Cell Mol Neurobiol. 2009, 29(5):609-19.
[22]李大鹏,于世英.长春新碱致神经病理性疼痛模型中胶质细胞及IL-1β、GDNF表达的变化[J].肿瘤防治研究,2007,34(2):93-95
[23]Cata JP, Weng HR, Dougherty PM. The effects of thalidomide and minocycline on taxol-induced hyperalgesia in rats. Brain Res. 2008 Sep 10;1229:100-10
[24] Balayssac D, Cayre A, Ling B,et al. Increase in morphine antinociceptive activity by a P-glycoprotein inhibitor in cisplatin-induced neuropathy. Neurosci Lett. 2009 Nov 6;465(1):108-12.
[25] Zhang N,Rogers TJ,Caterina M,et a1.Proinflammatory chemokines,such as C-C chemokine ligand 3, desensitize mu-opioid receptors on dorsal root ganglia neurons[J]. Immunol,2004, 173(1):594-599
[2] Xiao W, Boroujerdi A, Bennett GJ,et al. Chemotherapy-evoked painful peripheral neuropathy: analgesic effects of gabapentin and effects on expression of thealpha-2-delta type-1 calcium channel subunit.[J]. Neuroscience. 2007, 144(2):714-20.[3]
[3]Jorgensen HS. Studies on the neuroendocrine role of serotonin[J].Dan Med Bull.2007,54(4):266-288
[4] Francis C. Colpaert, Kristof Deseure. High-Efficacy 5-Hydroxytryptamine 1A Receptor Activation Counteracts Opioid Hyperallodynia and Affective Conditioning[J]' Pharmacol Exp Ther.2006, 316:892–899
[5] Obata H,Saito S,Sasaki M,et al. Antiallodynic effect of intrathecally administered 5-HT(2) agonists in rats with nerve ligation[J]. Pain, 2001, 90(1-2):73-179
[6] Karla P. Zeitz, Nicolas Guy, Annika B. Malmberg The 5-HT3 Subtype of Serotonin Receptor Contributes to Nociceptive Processing via a Novel Subset of Myelinated and Unmyelinated Nociceptors Journal Neuroscience, February 1, 2002, 22(3):1010-1019
[7] García-Alcocer G,Sarabia-Altamirano G, Martínez-Torres A,et al. Developmental expression of 5-HT 5A receptor mRNA in the rat brain[J]. Neurosci Lett, 2005; 379(2):101-105.
[8]陈晶,周亮,王亚云,等.坐骨神经分支选择性损伤模型大鼠脊髓背角内5-羟色胺4-7受体亚型mRNAs的表达变化[J].中国临床康复,2006;10(32):95-98.
[9] Wu S, Zhu M, Wang W, et al .Changes of the expression of 5-HT receptor subtype mRNAs in rat dorsal root ganglion by complete Freund's adjuvant-induced inflammation. Neurosci Lett, 2001, 20,307(3):183-186
[1] Chen JJ, Vasko MR,Wu X, et al. Multiple subtypes of serotonin receptors are expressed in rat sensory neurons in culture[J]. Pharmacol Exp Ther, 1998;287(3):1119-1127.
[2] Ohta T, Ikemi Y, Murakami M, et al. Potentiation of transient receptor potential V1functions by the activation of metabotropic 5-HT receptors in rat primary sensory neurons[J]. Physiol, 2006; 576(3):809-822.
[3]陈治军,田玉科,罗放.紫杉醇致大鼠外周NPP模型的建立[J]华中科技大学学报(医学版),2008, 37(6):785-790.
[4]Siau C, Xiao W, Bennett GJ. Paclitaxel- and vincristine-evoked painful peripheral neuropathies: loss of epidermal innervation and activation of Langerhans cells[J].Exp Neurol. 2006 ,201(2):507-514.
[5] Nishida K, Kuchiiwa S, Oiso S, et al. Up-regulation of matrix metalloproteinase-3 in the dorsal root ganglion of rats with paclitaxel-induced neuropathy[J].Cancer Sci.2008, 99(8):1618-1625.
[6] Peters CM, Jimenez-Andrade JM,Jonas BM,et al Intravenous paclitaxel administration in the rat induces a peripheral sensory neuropathy characterized by macrophage infiltration and injury to sensory neurons and their supporting cells[J]. Exp Neurol,2007,203(1):42-54.
[7]Xiao WH, Bennett GJ. Chemotherapy-evoked neuropathic pain: Abnormal spontaneous discharge in A-fiber and C-fiber primary afferent neurons and its suppression by acetyl-L-carnitine[J]. Pain.2008,135(3):262-270.
[8]Weng HR, Cordella JV, Dougherty PM.Changes in sensory processing in the spinal dorsal horn accompany vincristine-induced hyperalgesia and allodynia. [J].Pain.2003,103(1-2):131-8
[9]Xiao W, Boroujerdi A, Bennett GJ,et al. Chemotherapy-evoked painful peripheral neuropathy: analgesic effects of gabapentin and effects on expression of the alpha-2-delta type-1 calcium channel subunit.[J]. Neuroscience. 2007,144(2):714-20.
[10]李大鹏,于世英.长春新碱致神经病理性疼痛模型中胶质细胞及IL-1β、GDNF表达的变化[J].肿瘤防治研究,2007,34(2):93-95
[11]Weng HR, Cordella JV, Dougherty PM. Changes in sensory processing in the spinal dorsal horn accompany vincristine-induced hyperalgesia and allodynia[J].Pain, 2003, 103(1-2):131-138.
[12]Aley KO,Reichling DB,Levine JD. Vincristine hyperalgesia in the rat: a model of painful vincristine neuropathy in humans [J]. Neuroscience, 1996; 73(1):259-265.
[1]Natt F. siRNAs in drug discovery: target validation and beyond[J].Curr Opin Mol Ther,2007;9(3):242-7
[2]Naqvi AR, Islam MN, Choudhury NR, Haq QM. The fascinating world of RNA interference[J]. Int J Biol Sci. 2009,5(2):97-117.
[3]Amarzguioui M, Rossi JJ, Kim D. Approaches for chemically synthesized siRNA and vector-mediated RNAi[J]. FEBS Lett. 2005, 579(26):5974-5981.
[4]Vorburger SA, Hunt KK. Adenoviral gene therapy[J]. Oncologiest, 2002;7(1):46-59
[5]Huang B,Schiefer J,Sass C,et al. High-capacity adenoviral vector-mediated reduction of huntingtin aggregate load in vitro and in vivo[J]. Hum Gene Ther, 2007;18(4):303-311.
[6]Chen Y, Chen H, Hoffmann A,et al. Adenovirus-mediated small-Interference RNA for in vivo silencing of angiotensin AT1a receptors in mouse brain[J]. Hypertension,2006;47(2);230-237.
[7]Matthews DA, Cummings D, Evelegh C, et al. Development and use of a 293 cell line expressing lac repressor for the rescue of recombinant adenoviruses expressing high levels of rabies virus glycoprotein[J]. Gen Virol. 1999,80(pt2):345-353.
[8]Milligan ED, Hinde JL, Mehmert KK, et al. A method for increasing the viability of the external portion of lumbar catheters placed in the spinal subarachnoid space of rats[J]. Neurosci Methods,1999;90(1):8l-86
[9]Noda M, Yasuda S, Okada M, et al. Recombinant human serotonin 5A receptors stably expressed in C6 glioma cells couple to multiple signal transduction pathways[J]. Neurochem. 2003;84(2):222-232
[1] Cella D,Peterman A, Hudgens S, et al. Measuring the side effects of taxane therapy in oncology: the functional assessment of cancer therapy-taxane (FACT-taxane).[J].Cancer, 2003, 98(4): 822-831.
[2] Singhal M, Bakhshi S.Primary myositis coinciding with vincristine-induced neuropathic pain and urinary retention in rhabdomyosarcoma: an unusual occurrence.[J]. Pediatr Hematol Oncol,2008, 30(11):869.
[3]] Marcus AI, Peters U, Thomas SL,et al. Mitotic kinesin inhibitors induce mitotic arrest and cell death in Taxol-resistant and -sensitive cancer cells. [J]Biol Chem.2005,280(12):11569-11577.
[4] Joseph EK, Levine JD. Comparison of oxaliplatin- and cisplatin-induced painful peripheral neuropathy in the rat [J]. Pain, 2009,10(5):534-541.
[5]Park SB, Krishnan AV,Lin CS, et al. Mechanisms underlying chemotherapy-induced neurotoxicity and the potenetial for neuroprotective strategies[J].Curr Med Chem.2008, 15(29):3081-3094.
[6] Durie V, Mc Carson KE. Persistent Pain produces stress like alterations in hippocampal neurogenesis and gene expression.[J]. Pain, 2006, 7(8):544-555..
[7]陈治军,田玉科,罗放.紫杉醇致大鼠外周NPP模型的建立[J]华中科技大学学报(医学版),2008, 37(6):785-790.
[8]Siau C, Xiao W, Bennett GJ. Paclitaxel- and vincristine-evoked painful peripheral neuropathies: loss of epidermal innervation and activation of Langerhans cells[J].Exp Neurol. 2006 ,201(2):507-514.
[9] Topp KS, Tanner KD, Levine JD. Damage to the cytoskeleton of large diametersensory neurons and myelinated axons in vincristine-induced painful peripheral neuropathy in the rat[J].Comp Neurol. 2000, 424(4):563-576.
[10]Xiao WH, Bennett GJ. Chemotherapy-evoked neuropathic pain: Abnormal spontaneous discharge in A-fiber and C-fiber primary afferent neurons and its suppression by acetyl-L-carnitine[J]. Pain.2008,135(3):262-270.
[11]Chung JM,Chung K. Sodium channels and neuropathic pain[J]. Novartis Found Symp, 2004, 261:19-27.
[12]Nieto FR, Entrena JM, Cendan CM, et a1. Tetrodotoxin inhibits the development and expression of neurepathic pain induced by paclitaxel in mice[J]. Pain.,2008,137(3):520-531.
[13]Oh SB,Tran PB,Gillard SE, et a1. Chemokines and glycoprotein 120 produce pain hypersensitivity by directly exciting primary nociceptive neurons[J]. Neurosci,2001,21(14): 5027-5035.
[14] Nishida K, Kuchiiwa S, Oiso S, et al. Up-regulation of matrix metalloproteinase-3 in the dorsal root ganglion of rats with paclitaxel-induced neuropathy[J].Cancer Sci.2008, 99(8):1618-1625.
[15] Peters CM, Jimenez-Andrade JM,Jonas BM,et al Intravenous paclitaxel administration in the rat induces a peripheral sensory neuropathy characterized by macrophage infiltration and injury to sensory neurons and their supporting cells[J]. Exp Neurol,2007,203(1):42-54.
[16] Chizh BA,O'Donnell MB,Napolitano A,et al. The effects of the TRPV1 antagonist SB-705498 on TRPV1 receptor-mediated activity and inflammatory hyperalgesia in humans[J].Pain.2007 ,132(1-2):132-41.
[17] Ta LE, Bieber AJ, Carlton SM, et al.Transient Receptor Potential Vanilloid 1 is essential for cisplatin-induced heat hyperalgesia in mice[J].Mol Pain. 2010 ,6(1):15.
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