钙调蛋白激酶Ⅱ在神经病理痛中的作用及其痛觉调控通路概况
|
摘要
钙调蛋白激酶Ⅱ(Ca2+/calmodulin-dependent protein kinase,Ca MKⅡ)是一种多功能的丝氨酸/苏氨酸蛋白激酶,在神经元中大量存在,广泛参与疼痛调制。神经病理痛是一种由疾病或躯体感觉系统的损伤引起的慢性难治性疼痛。钙调蛋白激酶Ⅱ在中枢、外周神经病理痛、代谢型神经病理痛和药物引起神经病理痛等各种类型的神经病理痛的发生发展中发挥着重要的作用。本文拟将从钙调激酶Ⅱ介导的各型神经病理痛及其上下游的调控两个方面进行综述,以期为今后钙调蛋白激酶Ⅱ在神经病理痛领域的研究提供一定参考。
Ca~(2+)/calmodulin-dependent protein kinase Ⅱ( Ca MKII) is a multifunctional serine/threonine protein kinase in a large number of neurons and is widely involved in pain modulation. Neuropathic pain is chronic refractory pain caused by disease or damage to the somatosensory system. Ca MKII plays an important role in the occurrence and development of various types of neuropathic pain such as central,peripheral,diabetic and drug-induced neuropathic pain.This review focuses on the regulation of Ca MKII-mediated neuropathic pain and its upstream and downstream pathways to provide a reference for the future study of Ca MKII in the field of neuropathic pain.
Ca~(2+)/calmodulin-dependent protein kinase Ⅱ( Ca MKII) is a multifunctional serine/threonine protein kinase in a large number of neurons and is widely involved in pain modulation. Neuropathic pain is chronic refractory pain caused by disease or damage to the somatosensory system. Ca MKII plays an important role in the occurrence and development of various types of neuropathic pain such as central,peripheral,diabetic and drug-induced neuropathic pain.This review focuses on the regulation of Ca MKII-mediated neuropathic pain and its upstream and downstream pathways to provide a reference for the future study of Ca MKII in the field of neuropathic pain.
引文
[1] Soderling TR. Cam-kinases:Modulators of synaptic plasticity[J]. Curr Opin Neurobiol,2000,10(3):375-380.
[2] Kemp BE, Parker MW, Hu S, et al. Substrate and pseudosubstrate interactions with protein kinases:Determinants of specificity[J]. Trends Biochem Sci,1994,19(11):440-444.
[3] Lisman J,Schulman H,Cline H. The molecular basis of CaMKII function in synaptic and behavioural memory[J]. Nat Rev Neurosci,2002,3(3):175-190.
[4] Crown ED. The role of mitogen activated protein kinase signaling in microglia and neurons in the initiation and maintenance of chronic pain[J]. Exp Neurol,2012,234(2):330-339.
[5] Ataei N,Sabzghabaee AM,Movahedian A. Calcium/calmodulindependent protein kinase II is a ubiquitous molecule in human long-term memory synaptic plasticity:A systematic review[J].Int J Prev Med,2015,6:88.
[6] Liu XB, Murray KD. Neuronal excitability and calcium/calmodulin-dependent protein kinase type II:Location,location,location[J]. Epilepsia,2012,53(s1):45-52.
[7] Wayman GA,Tokumitsu H,Davare MA,et al. Analysis of CaM-kinase signaling in cells[J]. Cell Calcium,2011,50(1):1-8.
[8] Brüggemann I,Schulz S,Wiborny D,et al. Colocalization of theμ-opioid receptor and calcium/calmodulin-dependent kinase II in distinct pain-processing brain regions[J]. Brain Res Mol Brain Res,2000,85(1):239-250.
[9] Carlton SM. Localization of CaMKIIαin rat primary sensory neurons:Increase in inflammation[J]. Brain Res,2002,947(2):252-259.
[10] Carlton SM, Hargett GL. Stereological analysis of Ca2+/calmodulin-dependent protein kinase II alpha-containing dorsal root ganglion neurons in the rat:Colocalization with isolectin Griffonia simplicifolia, calcitonin gene-related peptide, or vanilloid receptor 1[J]. J Comp Neurol,2002,448(1):102-110.
[11] Kojundzic SL,Puljak L,Hogan Q,,et al. Depression of Ca2+/calmodulin-dependent protein kinase II in dorsal root ganglion neurons after spinal nerve ligation[J]. J Comp Neurol,2010,518(1):64-74.
[12] Garry EM,Moss A,Delaney A,et al. Neuropathic sensitization of behavioral reflexes and spinal NMDA receptor/cam receptor/CaM kinase II interactions are disrupted in PSD-95 mutant mice[J]. Curr Biol,2003,13(4):321-328.
[13] Dai Y,Wang H,Ogawa A,et al. Ca2+/calmodulin-dependent protein kinase II in the spinal cord contributes to neuropathic pain in a rat model of mononeuropathy[J]. Eur J Neurosci,2015,21(9):2467-2474.
[14] Hasegawa S,Kohro Y,Tsuda M,et al. Activation of cytosolic phospholipase A2in dorsal root ganglion neurons by Ca2+/calmodulin-dependent protein kinase II after peripheral nerve injury[J]. Mol Pain,2009,5(1):22.
[15] Chen Y,Luo F,Yang C,et al. Acute inhibition of Ca2+/calmodulin-dependent protein kinase II reverses experimental neuropathic pain in mice[J]. J Pharmacol Exp Ther,2009,330(2):650-659.
[16] Wang Y,Cheng X,Xu J,et al. Anti-hyperalgesic effect of CaMKII inhibitor is associated with downregulation of phosphorylated CREB in rat spinal cord[J]. J Anesth,2011,25(1):87-92.
[17] Bian H,Yu LC. Intra-nucleus accumbens administration of the calcium/calmodulin-dependent protein kinase II inhibitor AIP induced antinociception in rats with mononeuropathy[J].Neurosci Lett,2014,583:6-10.
[18] Bangaru MLY,Meng J,Kaiser DJ,et al. Differential expression of CaMKII isoforms and overall kinase activity in rat dorsal root ganglia after injury[J]. Neuroscience,2015,300:116-127.
[19] Ogawa A,Dai Y,Yamanaka H,et al. Ca2+/calmodulin-protein kinase IIalpha in the trigeminal subnucleus caudalis contributes to neuropathic pain following inferior alveolar nerve transection[J]. Exp Neurol,2005,192(2):310-319.
[20] Shimada SG,La Motte RH. Behavioral differentiation between itch and pain in mouse[J]. Pain,2008,139(3):681-687.
[21] Wang Y,Fu X,Huang L,et al. Increased asics expression via the Camkii-CREB pathway in a novel mouse model of trigeminal pain[J]. Cell Physiol Biochem,2018,46(2):568-578.
[22] Han D,Wu C,Xiong Q,et al. Anti-inflammatory mechanism of bone marrow mesenchymal stem cell transplantation in rat model of spinal cord injury[J]. Cell Biochem Biophys,2015,71(3):1341-1347.
[23] Siddall PJ,Loeser JD. Pain following spinal cord injury[J].Spinal Cord,2001,39(2):63-73.
[24] Frese A,Husstedt IW,Ringelstein EB,et al. Pharmacologic treatment of central post-stroke pain[J]. Clin J Pain,2006,22(3):252-260.
[25] Osterberg A,Boivie J,Thuomas KA. Central pain in multiple sclerosis-prevalence and clinical characteristics[J]. Eur J Pain,2005,9(5):531-542.
[26] Hulsebosch CE,Xu GY,Perezpolo JR,et al. Rodent model of chronic central pain after spinal cord contusion injury and effects of gabapentin[J]. J Neurotrauma,2000,17(12):1205-1217.
[27] Cadete MA,Temugin B,Stefnia F,et al. Lipoxin A4 inhibits microglial activation and reduces neuroinflammation and neuropathic pain after spinal cord hemisection[J]. J Neuroinflammation,2016,13(1):75.
[28] Yezierski RP,Liu S,Ruenes GL,et al. Excitotoxic spinal cord injury:Behavioral and morphological characteristics of a central pain model[J]. Pain,1998,75(1):141-155.
[29] Gwak YS,Hassler SE,Hulsebosch CE. Reactive oxygen species contribute to neuropathic pain and locomotor dysfunction via activation of CamKII in remote segments following spinal cord contusion injury in rats[J]. Pain,2013,154(9):1699-1708.
[30] Lu HF,Xu CY,Zhang L,et al. A new central post-stroke pain rat model:Autologous blood injected thalamic hemorrhage involved increased expression of P2X4 receptor[J]. Neurosci Lett,2018,687:124-130.
[31] Shih HC, Kuan YH, Shyu BC. Targeting brain-derived neurotrophic factor in the medial thalamus for the treatment of central poststroke pain in a rodent model[J]. Pain,2017,158(7):1302-1313.
[32] Doyle KP, Simon RP, Stenzel-Poore MP. Mechanisms of ischemic brain damage[J]. Neuropharmacology,2008,55(3):310-318.
[33] Boric M, Jelicic Kadic A, Ferhatovic L, et al. Calcium/calmodulin-dependent protein kinase in dorsal horn neurons in long-term diabetes[J]. Neuroreport,2013,24(17):992-996.
[34] Ferhatovic L,Banozic A,Kostic S,et al. Sex differences in pain-related behavior and expression of calcium/calmodulindependent protein kinase II in dorsal root ganglia of rats with diabetes type 1 and type 2[J]. Acta Histochem,2013,115(5):496-504.
[35] Boric M,Jelicic Kadic A,Puljak L. The expression of calcium/calmodulin-dependent protein kinase II in the dorsal horns of rats with type 1 and type 2 diabetes[J]. Neurosci Lett,2014,579:151-156.
[36] Ferhatovic L,Jelicic Kadic A,Boric M,et al. Changes of calcium/calmodulin-dependent protein kinase II expression in dorsal root ganglia during maturation in long-term diabetes[J].Histol Histopathol,2014,29(5):649-658.
[37] Jelicic Kadic A,Boric M,Ferhatovic L, et al. Intrathecal inhibition of calcium/calmodulin-dependent protein kinase II in diabetic neuropathy adversely affects pain-related behavior[J].Neurosci Lett,2013,554(1):126-130.
[38] Jelicic Kadic AJ,Boric M,Kostic S,et al. The effects of intraganglionic injection of calcium/calmodulin-dependent protein kinase II inhibitors on pain-related behavior in diabetic neuropathy[J]. Neuroscience,2014,256(1):302-308.
[39] Lucchesi W,Mizuno K,Giese KP. Novel insights into CaMKII function and regulation during memory formation[J]. Brain Res Bull,2011,85(1-2):2-8.
[40] Sasaki A,Mabuchi T,Serizawa K,et al. Different roles of nitric oxide synthase-1 and-2 between herpetic and postherpetic allodynia in mice[J]. Neuroscience,2007,150(2):459-466.
[41] Meller ST,Gebhart GF. Nitric oxide(no)and nociceptive processing in the spinal cord[J]. Pain,1993,52(2):127-136.
[42] Garthwaite J. Concepts of neural nitric oxide-mediated transmission[J]. Eur J Neurosci,2008,27(11):2783-2802.
[43] Sakurai M,Egashira N,Kawashiri T,et al. Oxaliplatin-induced neuropathy in the rat:Involvement of oxalate in cold hyperalgesia but not mechanical allodynia[J]. Pain,2009,147(1-3):165-174.
[44] Shirahama M,Ushio S,Egashira N,et al. Inhibition of Ca2+/calmodulin-dependent protein kinase II reverses oxaliplatininduced mechanical allodynia in rats[J]. Mol Pain,2012,8:26.
[45] Jiang M,Zhang W,Cheng C,et al. Intrathecal injection of KN93 attenuates paradoxical remifentanil-induced postoperative hyperalgesia by inhibiting spinal CaMKII phosphorylation in rats[J]. Pharmacol Biochem Behav,2015,134:35-41.
[46] Monshausen GB. Visualizing Ca2+signatures in plants[J]. Curr Opin Plant Biol,2012,15(6):677-682.
[47] Swulius MT,Waxham MN. Ca2+/calmodulin-dependent protein kinases[J]. Cell Mol Life Sci,2008,65(17):2637-2657.
[48] Erickson JR,Joiner ML,Guan X,et al. A dynamic pathway for calcium-independent activation of CaMKII by methionine oxidation[J]. Cell,2008,133(3):462-474.
[49] Liu X,Ma C,Xing R,et al. The calmodulin-dependent protein kinase II inhibitor KN-93 protects rat cerebral cortical neurons from N-methyl-D-aspartic acid-induced injury[J]. Neural Regen Res,2013,8(2):111-120.
[50] Matsumura S,Kunori S, Mabuchi T, et al. Impairment of CaMKII activation and attenuation of neuropathic pain in mice lacking NR2B phosphorylated at Tyr1472[J]. Eur J Neurosci,2010,32(5):798-810.
[51] Zhang Y,Li A,Xin J,et al. Electroacupuncture alleviates chemotherapy-induced pain through inhibiting phosphorylation of spinal CaMKII in rats[J]. Eur J Pain,2018,22(4):679-690.
[52] Andrei SR,Ghosh M,Sinharoy P,et al. TRPA1 ion channel stimulation enhances cardiomyocyte contractile function via a CaMKII-dependent pathway[J]. Channels(Austin),2017,11(6):587-603.
[53] Suo ZW,Fan QQ,Yang X,et al. Ca2+/calmodulin-dependent protein kinase II in spinal dorsal horn contributes to the pain hypersensitivity induced byγ-aminobutyric acid type a receptor inhibition[J]. J Neurosci Res,2013,91(11):1473-1482.
[54] Liu S,Mi WL,Li Q,et al. Spinal IL-33/ST2 signaling contributes to neuropathic pain via neuronal CaMKII-CREB and astroglial JAK2-STAT3 cascades in mice[J]. Anesthesiology,2015,123(5):1154-1169.
[55] Yao CY,Weng ZL,Zhang JC,et al. Interleukin-17a acts to maintain neuropathic pain through activation of CaMKII/CREB signaling in spinal neurons[J]. Mol Neurobiol,2016,53(6):3914-3926.
[56] Zhang J, Li N, Yu J, et al. Molecular cloning and characterization of a novel calcium/calmodulin-dependent protein kinase II inhibitor from human dendritic cells[J]. Biochem Biophys Res Commun,2001,285(2):229-234.
[57] Komeima K,Hayashi Y,Naito Y,et al. Inhibition of neuronal nitric-oxide synthase by calcium/calmodulin-dependent protein kinase II through Ser847 phosphorylation in NG108-15 neuronal cells[J]. J Biol Chem,2000,275(36):28139-28143.
[58] Rameau GA,Chiu LY,Ziff EB. NMDA receptor regulation of nNOS phosphorylation and induction of neuron death[J].Neurobiol Aging,2003,24(8):1123-1133.
[59] Tsuda M, Hasegawa S, Inoue K. P2x receptors-mediated cytosolic phospholipase A2activation in primary afferent sensory neurons contributes to neuropathic pain[J]. J Neurochem,2010,103(4):1408-1416.
[60] Ashpole NM, Herren AW, Ginsburg KS, et al. Ca2+/calmodulin-dependent protein kinase II(CaMKII)regulates cardiac sodium channel Na V1. 5 gating by multiple phosphorylation sites[J]. J Biol Chem,2012,287(24):19856-19869.
[61] Meffert MK,Chang JM,Wiltgen BJ,et al. NF-κB functions in synaptic signaling and behavior[J]. Nat Neurosci,2003,6(10):1072-1078.
[62] Li J,Wang P,Ying J,et al. Curcumin attenuates retinal vascular leakage by inhibiting calcium/calmodulin-dependent protein kinase II activity in streptozotocin-induced diabetes[J].Cell Physiol Biochem,2016,39(3):1196-1208.
[63] Fan W,Cooper NG. Glutamate-induced NFκB activation in the retina[J]. Invest Ophthalmol Vis Sci,2009,50(2):917-925.
[64] Xu GY,Huang LY. Ca2+/calmodulin-dependent protein kinase II potentiates ATP responses by promoting trafficking of P2X receptors[J]. Proc Natl Acad Sci U S A,2004,101(32):11868-11873.
[65] Chen XQ,Zhu JX,Wang Y,et al. CaMKIIαand caveolin-1cooperate to drive ATP-induced membrane delivery of the P2X3receptor[J]. J Mol Cell Biol,2014,6(2):140-153.
[2] Kemp BE, Parker MW, Hu S, et al. Substrate and pseudosubstrate interactions with protein kinases:Determinants of specificity[J]. Trends Biochem Sci,1994,19(11):440-444.
[3] Lisman J,Schulman H,Cline H. The molecular basis of CaMKII function in synaptic and behavioural memory[J]. Nat Rev Neurosci,2002,3(3):175-190.
[4] Crown ED. The role of mitogen activated protein kinase signaling in microglia and neurons in the initiation and maintenance of chronic pain[J]. Exp Neurol,2012,234(2):330-339.
[5] Ataei N,Sabzghabaee AM,Movahedian A. Calcium/calmodulindependent protein kinase II is a ubiquitous molecule in human long-term memory synaptic plasticity:A systematic review[J].Int J Prev Med,2015,6:88.
[6] Liu XB, Murray KD. Neuronal excitability and calcium/calmodulin-dependent protein kinase type II:Location,location,location[J]. Epilepsia,2012,53(s1):45-52.
[7] Wayman GA,Tokumitsu H,Davare MA,et al. Analysis of CaM-kinase signaling in cells[J]. Cell Calcium,2011,50(1):1-8.
[8] Brüggemann I,Schulz S,Wiborny D,et al. Colocalization of theμ-opioid receptor and calcium/calmodulin-dependent kinase II in distinct pain-processing brain regions[J]. Brain Res Mol Brain Res,2000,85(1):239-250.
[9] Carlton SM. Localization of CaMKIIαin rat primary sensory neurons:Increase in inflammation[J]. Brain Res,2002,947(2):252-259.
[10] Carlton SM, Hargett GL. Stereological analysis of Ca2+/calmodulin-dependent protein kinase II alpha-containing dorsal root ganglion neurons in the rat:Colocalization with isolectin Griffonia simplicifolia, calcitonin gene-related peptide, or vanilloid receptor 1[J]. J Comp Neurol,2002,448(1):102-110.
[11] Kojundzic SL,Puljak L,Hogan Q,,et al. Depression of Ca2+/calmodulin-dependent protein kinase II in dorsal root ganglion neurons after spinal nerve ligation[J]. J Comp Neurol,2010,518(1):64-74.
[12] Garry EM,Moss A,Delaney A,et al. Neuropathic sensitization of behavioral reflexes and spinal NMDA receptor/cam receptor/CaM kinase II interactions are disrupted in PSD-95 mutant mice[J]. Curr Biol,2003,13(4):321-328.
[13] Dai Y,Wang H,Ogawa A,et al. Ca2+/calmodulin-dependent protein kinase II in the spinal cord contributes to neuropathic pain in a rat model of mononeuropathy[J]. Eur J Neurosci,2015,21(9):2467-2474.
[14] Hasegawa S,Kohro Y,Tsuda M,et al. Activation of cytosolic phospholipase A2in dorsal root ganglion neurons by Ca2+/calmodulin-dependent protein kinase II after peripheral nerve injury[J]. Mol Pain,2009,5(1):22.
[15] Chen Y,Luo F,Yang C,et al. Acute inhibition of Ca2+/calmodulin-dependent protein kinase II reverses experimental neuropathic pain in mice[J]. J Pharmacol Exp Ther,2009,330(2):650-659.
[16] Wang Y,Cheng X,Xu J,et al. Anti-hyperalgesic effect of CaMKII inhibitor is associated with downregulation of phosphorylated CREB in rat spinal cord[J]. J Anesth,2011,25(1):87-92.
[17] Bian H,Yu LC. Intra-nucleus accumbens administration of the calcium/calmodulin-dependent protein kinase II inhibitor AIP induced antinociception in rats with mononeuropathy[J].Neurosci Lett,2014,583:6-10.
[18] Bangaru MLY,Meng J,Kaiser DJ,et al. Differential expression of CaMKII isoforms and overall kinase activity in rat dorsal root ganglia after injury[J]. Neuroscience,2015,300:116-127.
[19] Ogawa A,Dai Y,Yamanaka H,et al. Ca2+/calmodulin-protein kinase IIalpha in the trigeminal subnucleus caudalis contributes to neuropathic pain following inferior alveolar nerve transection[J]. Exp Neurol,2005,192(2):310-319.
[20] Shimada SG,La Motte RH. Behavioral differentiation between itch and pain in mouse[J]. Pain,2008,139(3):681-687.
[21] Wang Y,Fu X,Huang L,et al. Increased asics expression via the Camkii-CREB pathway in a novel mouse model of trigeminal pain[J]. Cell Physiol Biochem,2018,46(2):568-578.
[22] Han D,Wu C,Xiong Q,et al. Anti-inflammatory mechanism of bone marrow mesenchymal stem cell transplantation in rat model of spinal cord injury[J]. Cell Biochem Biophys,2015,71(3):1341-1347.
[23] Siddall PJ,Loeser JD. Pain following spinal cord injury[J].Spinal Cord,2001,39(2):63-73.
[24] Frese A,Husstedt IW,Ringelstein EB,et al. Pharmacologic treatment of central post-stroke pain[J]. Clin J Pain,2006,22(3):252-260.
[25] Osterberg A,Boivie J,Thuomas KA. Central pain in multiple sclerosis-prevalence and clinical characteristics[J]. Eur J Pain,2005,9(5):531-542.
[26] Hulsebosch CE,Xu GY,Perezpolo JR,et al. Rodent model of chronic central pain after spinal cord contusion injury and effects of gabapentin[J]. J Neurotrauma,2000,17(12):1205-1217.
[27] Cadete MA,Temugin B,Stefnia F,et al. Lipoxin A4 inhibits microglial activation and reduces neuroinflammation and neuropathic pain after spinal cord hemisection[J]. J Neuroinflammation,2016,13(1):75.
[28] Yezierski RP,Liu S,Ruenes GL,et al. Excitotoxic spinal cord injury:Behavioral and morphological characteristics of a central pain model[J]. Pain,1998,75(1):141-155.
[29] Gwak YS,Hassler SE,Hulsebosch CE. Reactive oxygen species contribute to neuropathic pain and locomotor dysfunction via activation of CamKII in remote segments following spinal cord contusion injury in rats[J]. Pain,2013,154(9):1699-1708.
[30] Lu HF,Xu CY,Zhang L,et al. A new central post-stroke pain rat model:Autologous blood injected thalamic hemorrhage involved increased expression of P2X4 receptor[J]. Neurosci Lett,2018,687:124-130.
[31] Shih HC, Kuan YH, Shyu BC. Targeting brain-derived neurotrophic factor in the medial thalamus for the treatment of central poststroke pain in a rodent model[J]. Pain,2017,158(7):1302-1313.
[32] Doyle KP, Simon RP, Stenzel-Poore MP. Mechanisms of ischemic brain damage[J]. Neuropharmacology,2008,55(3):310-318.
[33] Boric M, Jelicic Kadic A, Ferhatovic L, et al. Calcium/calmodulin-dependent protein kinase in dorsal horn neurons in long-term diabetes[J]. Neuroreport,2013,24(17):992-996.
[34] Ferhatovic L,Banozic A,Kostic S,et al. Sex differences in pain-related behavior and expression of calcium/calmodulindependent protein kinase II in dorsal root ganglia of rats with diabetes type 1 and type 2[J]. Acta Histochem,2013,115(5):496-504.
[35] Boric M,Jelicic Kadic A,Puljak L. The expression of calcium/calmodulin-dependent protein kinase II in the dorsal horns of rats with type 1 and type 2 diabetes[J]. Neurosci Lett,2014,579:151-156.
[36] Ferhatovic L,Jelicic Kadic A,Boric M,et al. Changes of calcium/calmodulin-dependent protein kinase II expression in dorsal root ganglia during maturation in long-term diabetes[J].Histol Histopathol,2014,29(5):649-658.
[37] Jelicic Kadic A,Boric M,Ferhatovic L, et al. Intrathecal inhibition of calcium/calmodulin-dependent protein kinase II in diabetic neuropathy adversely affects pain-related behavior[J].Neurosci Lett,2013,554(1):126-130.
[38] Jelicic Kadic AJ,Boric M,Kostic S,et al. The effects of intraganglionic injection of calcium/calmodulin-dependent protein kinase II inhibitors on pain-related behavior in diabetic neuropathy[J]. Neuroscience,2014,256(1):302-308.
[39] Lucchesi W,Mizuno K,Giese KP. Novel insights into CaMKII function and regulation during memory formation[J]. Brain Res Bull,2011,85(1-2):2-8.
[40] Sasaki A,Mabuchi T,Serizawa K,et al. Different roles of nitric oxide synthase-1 and-2 between herpetic and postherpetic allodynia in mice[J]. Neuroscience,2007,150(2):459-466.
[41] Meller ST,Gebhart GF. Nitric oxide(no)and nociceptive processing in the spinal cord[J]. Pain,1993,52(2):127-136.
[42] Garthwaite J. Concepts of neural nitric oxide-mediated transmission[J]. Eur J Neurosci,2008,27(11):2783-2802.
[43] Sakurai M,Egashira N,Kawashiri T,et al. Oxaliplatin-induced neuropathy in the rat:Involvement of oxalate in cold hyperalgesia but not mechanical allodynia[J]. Pain,2009,147(1-3):165-174.
[44] Shirahama M,Ushio S,Egashira N,et al. Inhibition of Ca2+/calmodulin-dependent protein kinase II reverses oxaliplatininduced mechanical allodynia in rats[J]. Mol Pain,2012,8:26.
[45] Jiang M,Zhang W,Cheng C,et al. Intrathecal injection of KN93 attenuates paradoxical remifentanil-induced postoperative hyperalgesia by inhibiting spinal CaMKII phosphorylation in rats[J]. Pharmacol Biochem Behav,2015,134:35-41.
[46] Monshausen GB. Visualizing Ca2+signatures in plants[J]. Curr Opin Plant Biol,2012,15(6):677-682.
[47] Swulius MT,Waxham MN. Ca2+/calmodulin-dependent protein kinases[J]. Cell Mol Life Sci,2008,65(17):2637-2657.
[48] Erickson JR,Joiner ML,Guan X,et al. A dynamic pathway for calcium-independent activation of CaMKII by methionine oxidation[J]. Cell,2008,133(3):462-474.
[49] Liu X,Ma C,Xing R,et al. The calmodulin-dependent protein kinase II inhibitor KN-93 protects rat cerebral cortical neurons from N-methyl-D-aspartic acid-induced injury[J]. Neural Regen Res,2013,8(2):111-120.
[50] Matsumura S,Kunori S, Mabuchi T, et al. Impairment of CaMKII activation and attenuation of neuropathic pain in mice lacking NR2B phosphorylated at Tyr1472[J]. Eur J Neurosci,2010,32(5):798-810.
[51] Zhang Y,Li A,Xin J,et al. Electroacupuncture alleviates chemotherapy-induced pain through inhibiting phosphorylation of spinal CaMKII in rats[J]. Eur J Pain,2018,22(4):679-690.
[52] Andrei SR,Ghosh M,Sinharoy P,et al. TRPA1 ion channel stimulation enhances cardiomyocyte contractile function via a CaMKII-dependent pathway[J]. Channels(Austin),2017,11(6):587-603.
[53] Suo ZW,Fan QQ,Yang X,et al. Ca2+/calmodulin-dependent protein kinase II in spinal dorsal horn contributes to the pain hypersensitivity induced byγ-aminobutyric acid type a receptor inhibition[J]. J Neurosci Res,2013,91(11):1473-1482.
[54] Liu S,Mi WL,Li Q,et al. Spinal IL-33/ST2 signaling contributes to neuropathic pain via neuronal CaMKII-CREB and astroglial JAK2-STAT3 cascades in mice[J]. Anesthesiology,2015,123(5):1154-1169.
[55] Yao CY,Weng ZL,Zhang JC,et al. Interleukin-17a acts to maintain neuropathic pain through activation of CaMKII/CREB signaling in spinal neurons[J]. Mol Neurobiol,2016,53(6):3914-3926.
[56] Zhang J, Li N, Yu J, et al. Molecular cloning and characterization of a novel calcium/calmodulin-dependent protein kinase II inhibitor from human dendritic cells[J]. Biochem Biophys Res Commun,2001,285(2):229-234.
[57] Komeima K,Hayashi Y,Naito Y,et al. Inhibition of neuronal nitric-oxide synthase by calcium/calmodulin-dependent protein kinase II through Ser847 phosphorylation in NG108-15 neuronal cells[J]. J Biol Chem,2000,275(36):28139-28143.
[58] Rameau GA,Chiu LY,Ziff EB. NMDA receptor regulation of nNOS phosphorylation and induction of neuron death[J].Neurobiol Aging,2003,24(8):1123-1133.
[59] Tsuda M, Hasegawa S, Inoue K. P2x receptors-mediated cytosolic phospholipase A2activation in primary afferent sensory neurons contributes to neuropathic pain[J]. J Neurochem,2010,103(4):1408-1416.
[60] Ashpole NM, Herren AW, Ginsburg KS, et al. Ca2+/calmodulin-dependent protein kinase II(CaMKII)regulates cardiac sodium channel Na V1. 5 gating by multiple phosphorylation sites[J]. J Biol Chem,2012,287(24):19856-19869.
[61] Meffert MK,Chang JM,Wiltgen BJ,et al. NF-κB functions in synaptic signaling and behavior[J]. Nat Neurosci,2003,6(10):1072-1078.
[62] Li J,Wang P,Ying J,et al. Curcumin attenuates retinal vascular leakage by inhibiting calcium/calmodulin-dependent protein kinase II activity in streptozotocin-induced diabetes[J].Cell Physiol Biochem,2016,39(3):1196-1208.
[63] Fan W,Cooper NG. Glutamate-induced NFκB activation in the retina[J]. Invest Ophthalmol Vis Sci,2009,50(2):917-925.
[64] Xu GY,Huang LY. Ca2+/calmodulin-dependent protein kinase II potentiates ATP responses by promoting trafficking of P2X receptors[J]. Proc Natl Acad Sci U S A,2004,101(32):11868-11873.
[65] Chen XQ,Zhu JX,Wang Y,et al. CaMKIIαand caveolin-1cooperate to drive ATP-induced membrane delivery of the P2X3receptor[J]. J Mol Cell Biol,2014,6(2):140-153.