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Published in: Molecular Pain 1/2013

Open Access 01-12-2013 | Research

Activation of cyclin-dependent kinase 5 mediates orofacial mechanical hyperalgesia

Authors: Michaela Prochazkova, Anita Terse, Niranjana D Amin, Bradford Hall, Elias Utreras, Harish C Pant, Ashok B Kulkarni

Published in: Molecular Pain | Issue 1/2013

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Abstract

Background

Cyclin-dependent kinase 5 (Cdk5) is a unique member of the serine/threonine kinase family. This kinase plays an important role in neuronal development, and deregulation of its activity leads to neurodegenerative disorders. Cdk5 also serves an important function in the regulation of nociceptive signaling. Our previous studies revealed that the expression of Cdk5 and its activator, p35, is upregulated in nociceptive neurons during peripheral inflammation. The aim of the present study was to characterize the involvement of Cdk5 in orofacial pain. Since mechanical hyperalgesia is the distinctive sign of many orofacial pain conditions, we adapted an existing orofacial stimulation test to assess the behavioral responses to mechanical stimulation in the trigeminal region of the transgenic mice with either reduced or increased Cdk5 activity.

Results

Mice overexpressing or lacking p35, an activator of Cdk5, showed altered phenotype in response to noxious mechanical stimulation in the trigeminal area. Mice with increased Cdk5 activity displayed aversive behavior to mechanical stimulation as indicated by a significant decrease in reward licking events and licking time. The number of reward licking/facial contact events was significantly decreased in these mice as the mechanical intensity increased. By contrast, mice deficient in Cdk5 activity displayed mechanical hypoalgesia.

Conclusions

Collectively, our findings demonstrate for the first time the important role of Cdk5 in orofacial mechanical nociception. Modulation of Cdk5 activity in primary sensory neurons makes it an attractive potential target for the development of novel analgesics that could be used to treat multiple orofacial pain conditions.
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Literature
1.
go back to reference Madland G, Newton-John T, Feinmann C: Chronic idiopathic orofacial pain: I: what is the evidence base? Br Dent J 2001, 191: 22–24.PubMed Madland G, Newton-John T, Feinmann C: Chronic idiopathic orofacial pain: I: what is the evidence base? Br Dent J 2001, 191: 22–24.PubMed
2.
3.
go back to reference Romero-Reyes M, Akerman S, Nguyen E, Vijjeswarapu A, Hom B, Dong HW, Charles AC: Spontaneous behavioral responses in the orofacial region: a model of trigeminal pain in mouse. Headache 2013, 53: 137–151. 10.1111/j.1526-4610.2012.02226.xPubMedCentralCrossRefPubMed Romero-Reyes M, Akerman S, Nguyen E, Vijjeswarapu A, Hom B, Dong HW, Charles AC: Spontaneous behavioral responses in the orofacial region: a model of trigeminal pain in mouse. Headache 2013, 53: 137–151. 10.1111/j.1526-4610.2012.02226.xPubMedCentralCrossRefPubMed
4.
go back to reference Yasuda M, Shinoda M, Kiyomoto M, Honda K, Suzuki A, Tamagawa T, Kaji K, Kimoto S, Iwata K: P2X3 receptor mediates ectopic mechanical allodynia with inflamed lower lip in mice. Neurosci Lett 2012, 528: 67–72. 10.1016/j.neulet.2012.08.067CrossRefPubMed Yasuda M, Shinoda M, Kiyomoto M, Honda K, Suzuki A, Tamagawa T, Kaji K, Kimoto S, Iwata K: P2X3 receptor mediates ectopic mechanical allodynia with inflamed lower lip in mice. Neurosci Lett 2012, 528: 67–72. 10.1016/j.neulet.2012.08.067CrossRefPubMed
5.
go back to reference Poh KW, Lutfun N, Manikandan J, Ong WY, Yeo JF: Global gene expression analysis in the mouse brainstem after hyperalgesia induced by facial carrageenan injection–evidence for a form of neurovascular coupling? Pain 2009, 142: 133–141. 10.1016/j.pain.2008.12.029CrossRefPubMed Poh KW, Lutfun N, Manikandan J, Ong WY, Yeo JF: Global gene expression analysis in the mouse brainstem after hyperalgesia induced by facial carrageenan injection–evidence for a form of neurovascular coupling? Pain 2009, 142: 133–141. 10.1016/j.pain.2008.12.029CrossRefPubMed
6.
go back to reference Poh KW, Yeo JF, Stohler CS, Ong WY: Comprehensive gene expression profiling in the prefrontal cortex links immune activation and neutrophil infiltration to antinociception. J Neurosci 2012, 32: 35–45. 10.1523/JNEUROSCI.2389-11.2012CrossRefPubMed Poh KW, Yeo JF, Stohler CS, Ong WY: Comprehensive gene expression profiling in the prefrontal cortex links immune activation and neutrophil infiltration to antinociception. J Neurosci 2012, 32: 35–45. 10.1523/JNEUROSCI.2389-11.2012CrossRefPubMed
7.
go back to reference Bornhof M, Ihmsen H, Schwilden H, Yeomans DC, Tzabazis A: The orofacial formalin test in mice revisited–effects of formalin concentration, age, morphine and analysis method. J Pain 2011, 12: 633–639. 10.1016/j.jpain.2010.11.009CrossRefPubMed Bornhof M, Ihmsen H, Schwilden H, Yeomans DC, Tzabazis A: The orofacial formalin test in mice revisited–effects of formalin concentration, age, morphine and analysis method. J Pain 2011, 12: 633–639. 10.1016/j.jpain.2010.11.009CrossRefPubMed
8.
go back to reference Luccarini P, Childeric A, Gaydier AM, Voisin D, Dallel R: The orofacial formalin test in the mouse: a behavioral model for studying physiology and modulation of trigeminal nociception. J Pain 2006, 7: 908–914. 10.1016/j.jpain.2006.04.010CrossRefPubMed Luccarini P, Childeric A, Gaydier AM, Voisin D, Dallel R: The orofacial formalin test in the mouse: a behavioral model for studying physiology and modulation of trigeminal nociception. J Pain 2006, 7: 908–914. 10.1016/j.jpain.2006.04.010CrossRefPubMed
9.
go back to reference Miranda HF, Noriega V, Sierralta F, Prieto JC: Interaction between dexibuprofen and dexketoprofen in the orofacial formalin test in mice. Pharmacol Biochem Behav 2011, 97: 423–427. 10.1016/j.pbb.2010.09.017CrossRefPubMed Miranda HF, Noriega V, Sierralta F, Prieto JC: Interaction between dexibuprofen and dexketoprofen in the orofacial formalin test in mice. Pharmacol Biochem Behav 2011, 97: 423–427. 10.1016/j.pbb.2010.09.017CrossRefPubMed
10.
go back to reference Miranda HF, Noriega V, Zepeda RJ, Sierralta F, Prieto JC: Systemic synergism between codeine and morphine in three pain models in mice. Pharmacol Rep 2013, 65: 80–88.CrossRefPubMed Miranda HF, Noriega V, Zepeda RJ, Sierralta F, Prieto JC: Systemic synergism between codeine and morphine in three pain models in mice. Pharmacol Rep 2013, 65: 80–88.CrossRefPubMed
11.
go back to reference Cha M, Kohan KJ, Zuo X, Ling JX, Gu JG: Assessment of chronic trigeminal neuropathic pain by the orofacial operant test in rats. Behav Brain Res 2012, 234: 82–90. 10.1016/j.bbr.2012.06.020PubMedCentralCrossRefPubMed Cha M, Kohan KJ, Zuo X, Ling JX, Gu JG: Assessment of chronic trigeminal neuropathic pain by the orofacial operant test in rats. Behav Brain Res 2012, 234: 82–90. 10.1016/j.bbr.2012.06.020PubMedCentralCrossRefPubMed
12.
go back to reference Krzyzanowska A, Pittolo S, Cabrerizo M, Sanchez-Lopez J, Krishnasamy S, Venero C, Avendano C: Assessing nociceptive sensitivity in mouse models of inflammatory and neuropathic trigeminal pain. J Neurosci Methods 2011, 201: 46–54. 10.1016/j.jneumeth.2011.07.006CrossRefPubMed Krzyzanowska A, Pittolo S, Cabrerizo M, Sanchez-Lopez J, Krishnasamy S, Venero C, Avendano C: Assessing nociceptive sensitivity in mouse models of inflammatory and neuropathic trigeminal pain. J Neurosci Methods 2011, 201: 46–54. 10.1016/j.jneumeth.2011.07.006CrossRefPubMed
13.
go back to reference Rossi HL, Jenkins AC, Kaufman J, Bhattacharyya I, Caudle RM, Neubert JK: Characterization of bilateral trigeminal constriction injury using an operant facial pain assay. Neuroscience 2012, 224: 294–306.CrossRefPubMed Rossi HL, Jenkins AC, Kaufman J, Bhattacharyya I, Caudle RM, Neubert JK: Characterization of bilateral trigeminal constriction injury using an operant facial pain assay. Neuroscience 2012, 224: 294–306.CrossRefPubMed
14.
go back to reference Teodoro FC, Tronco Junior MF, Zampronio AR, Martini AC, Rae GA, Chichorro JG: Peripheral substance P and neurokinin-1 receptors have a role in inflammatory and neuropathic orofacial pain models. Neuropeptides 2013, 47: 199–206. 10.1016/j.npep.2012.10.005CrossRefPubMed Teodoro FC, Tronco Junior MF, Zampronio AR, Martini AC, Rae GA, Chichorro JG: Peripheral substance P and neurokinin-1 receptors have a role in inflammatory and neuropathic orofacial pain models. Neuropeptides 2013, 47: 199–206. 10.1016/j.npep.2012.10.005CrossRefPubMed
15.
go back to reference Neubert JK, King C, Malphurs W, Wong F, Weaver JP, Jenkins AC, Rossi HL, Caudle RM: Characterization of mouse orofacial pain and the effects of lesioning TRPV1-expressing neurons on operant behavior. Mol Pain 2008, 4: 43. 10.1186/1744-8069-4-43PubMedCentralCrossRefPubMed Neubert JK, King C, Malphurs W, Wong F, Weaver JP, Jenkins AC, Rossi HL, Caudle RM: Characterization of mouse orofacial pain and the effects of lesioning TRPV1-expressing neurons on operant behavior. Mol Pain 2008, 4: 43. 10.1186/1744-8069-4-43PubMedCentralCrossRefPubMed
16.
go back to reference Neubert JK, Widmer CG, Malphurs W, Rossi HL, Vierck CJ Jr, Caudle RM: Use of a novel thermal operant behavioral assay for characterization of orofacial pain sensitivity. Pain 2005, 116: 386–395. 10.1016/j.pain.2005.05.011CrossRefPubMed Neubert JK, Widmer CG, Malphurs W, Rossi HL, Vierck CJ Jr, Caudle RM: Use of a novel thermal operant behavioral assay for characterization of orofacial pain sensitivity. Pain 2005, 116: 386–395. 10.1016/j.pain.2005.05.011CrossRefPubMed
17.
go back to reference Nolan TA, Hester J, Bokrand-Donatelli Y, Caudle RM, Neubert K: Adaptation of novel operant orofacial testing system to characterize both mechanical and thermal pain. Behav Brain Res 2011, 217: 477–480. 10.1016/j.bbr.2010.10.022PubMedCentralCrossRefPubMed Nolan TA, Hester J, Bokrand-Donatelli Y, Caudle RM, Neubert K: Adaptation of novel operant orofacial testing system to characterize both mechanical and thermal pain. Behav Brain Res 2011, 217: 477–480. 10.1016/j.bbr.2010.10.022PubMedCentralCrossRefPubMed
18.
go back to reference Rossi HL, Vierck CJ Jr, Caudle RM, Neubert JK: Characterization of cold sensitivity and thermal preference using an operant orofacial assay. Mol Pain 2006, 2: 37. 10.1186/1744-8069-2-37PubMedCentralCrossRefPubMed Rossi HL, Vierck CJ Jr, Caudle RM, Neubert JK: Characterization of cold sensitivity and thermal preference using an operant orofacial assay. Mol Pain 2006, 2: 37. 10.1186/1744-8069-2-37PubMedCentralCrossRefPubMed
19.
go back to reference Dhariwala FA, Rajadhyaksha MS: An unusual member of the Cdk family: Cdk5. Cell Mol Neurobiol 2008, 28: 351–369. 10.1007/s10571-007-9242-1CrossRefPubMed Dhariwala FA, Rajadhyaksha MS: An unusual member of the Cdk family: Cdk5. Cell Mol Neurobiol 2008, 28: 351–369. 10.1007/s10571-007-9242-1CrossRefPubMed
20.
21.
go back to reference Lalioti V, Pulido D, Sandoval IV: Cdk5, the multifunctional surveyor. Cell Cycle 2010, 9: 284–311. 10.4161/cc.9.2.10466CrossRefPubMed Lalioti V, Pulido D, Sandoval IV: Cdk5, the multifunctional surveyor. Cell Cycle 2010, 9: 284–311. 10.4161/cc.9.2.10466CrossRefPubMed
22.
go back to reference Liebl J, Furst R, Vollmar AM, Zahler S: Twice switched at birth: cell cycle-independent roles of the “neuron-specific” cyclin-dependent kinase 5 (Cdk5) in non-neuronal cells. Cell Signal 2011, 23: 1698–1707. 10.1016/j.cellsig.2011.06.020CrossRefPubMed Liebl J, Furst R, Vollmar AM, Zahler S: Twice switched at birth: cell cycle-independent roles of the “neuron-specific” cyclin-dependent kinase 5 (Cdk5) in non-neuronal cells. Cell Signal 2011, 23: 1698–1707. 10.1016/j.cellsig.2011.06.020CrossRefPubMed
23.
go back to reference Su SC, Tsai LH: Cyclin-dependent kinases in brain development and disease. Annu Rev Cell Dev Biol 2011, 27: 465–491. 10.1146/annurev-cellbio-092910-154023CrossRefPubMed Su SC, Tsai LH: Cyclin-dependent kinases in brain development and disease. Annu Rev Cell Dev Biol 2011, 27: 465–491. 10.1146/annurev-cellbio-092910-154023CrossRefPubMed
24.
go back to reference Arif A: Extraneuronal activities and regulatory mechanisms of the atypical cyclin-dependent kinase Cdk5. Biochem Pharmacol 2012, 84: 985–993. 10.1016/j.bcp.2012.06.027CrossRefPubMed Arif A: Extraneuronal activities and regulatory mechanisms of the atypical cyclin-dependent kinase Cdk5. Biochem Pharmacol 2012, 84: 985–993. 10.1016/j.bcp.2012.06.027CrossRefPubMed
25.
go back to reference Contreras-Vallejos E, Utreras E, Gonzalez-Billault C: Going out of the brain: non-nervous system physiological and pathological functions of Cdk5. Cell Signal 2012, 24: 44–52. 10.1016/j.cellsig.2011.08.022CrossRefPubMed Contreras-Vallejos E, Utreras E, Gonzalez-Billault C: Going out of the brain: non-nervous system physiological and pathological functions of Cdk5. Cell Signal 2012, 24: 44–52. 10.1016/j.cellsig.2011.08.022CrossRefPubMed
26.
go back to reference Rosales JL, Lee KY: Extraneuronal roles of cyclin-dependent kinase 5. Bioessays 2006, 28: 1023–1034. 10.1002/bies.20473CrossRefPubMed Rosales JL, Lee KY: Extraneuronal roles of cyclin-dependent kinase 5. Bioessays 2006, 28: 1023–1034. 10.1002/bies.20473CrossRefPubMed
27.
go back to reference Ohshima T, Ward JM, Huh CG, Longenecker G, Veeranna , Pant HC, Brady RO, Martin LJ, Kulkarni AB: Targeted disruption of the cyclin-dependent kinase 5 gene results in abnormal corticogenesis, neuronal pathology and perinatal death. Proc Natl Acad Sci USA 1996, 93: 11173–11178. 10.1073/pnas.93.20.11173PubMedCentralCrossRefPubMed Ohshima T, Ward JM, Huh CG, Longenecker G, Veeranna , Pant HC, Brady RO, Martin LJ, Kulkarni AB: Targeted disruption of the cyclin-dependent kinase 5 gene results in abnormal corticogenesis, neuronal pathology and perinatal death. Proc Natl Acad Sci USA 1996, 93: 11173–11178. 10.1073/pnas.93.20.11173PubMedCentralCrossRefPubMed
28.
go back to reference Takahashi S, Ohshima T, Cho A, Sreenath T, Iadarola MJ, Pant HC, Kim Y, Nairn AC, Brady RO, Greengard P, Kulkarni AB: Increased activity of cyclin-dependent kinase 5 leads to attenuation of cocaine-mediated dopamine signaling. Proc Natl Acad Sci USA 2005, 102: 1737–1742. 10.1073/pnas.0409456102PubMedCentralCrossRefPubMed Takahashi S, Ohshima T, Cho A, Sreenath T, Iadarola MJ, Pant HC, Kim Y, Nairn AC, Brady RO, Greengard P, Kulkarni AB: Increased activity of cyclin-dependent kinase 5 leads to attenuation of cocaine-mediated dopamine signaling. Proc Natl Acad Sci USA 2005, 102: 1737–1742. 10.1073/pnas.0409456102PubMedCentralCrossRefPubMed
29.
go back to reference Chae T, Kwon YT, Bronson R, Dikkes P, Li E, Tsai LH: Mice lacking p35, a neuronal specific activator of Cdk5, display cortical lamination defects, seizures, and adult lethality. Neuron 1997, 18: 29–42. 10.1016/S0896-6273(01)80044-1CrossRefPubMed Chae T, Kwon YT, Bronson R, Dikkes P, Li E, Tsai LH: Mice lacking p35, a neuronal specific activator of Cdk5, display cortical lamination defects, seizures, and adult lethality. Neuron 1997, 18: 29–42. 10.1016/S0896-6273(01)80044-1CrossRefPubMed
30.
go back to reference Pareek TK, Keller J, Kesavapany S, Agarwal N, Kuner R, Pant HC, Iadarola MJ, Brady RO, Kulkarni AB: Cyclin-dependent kinase 5 modulates nociceptive signaling through direct phosphorylation of transient receptor potential vanilloid 1. Proc Natl Acad Sci USA 2007, 104: 660–665. 10.1073/pnas.0609916104PubMedCentralCrossRefPubMed Pareek TK, Keller J, Kesavapany S, Agarwal N, Kuner R, Pant HC, Iadarola MJ, Brady RO, Kulkarni AB: Cyclin-dependent kinase 5 modulates nociceptive signaling through direct phosphorylation of transient receptor potential vanilloid 1. Proc Natl Acad Sci USA 2007, 104: 660–665. 10.1073/pnas.0609916104PubMedCentralCrossRefPubMed
31.
go back to reference Yang YR, He Y, Zhang Y, Li Y, Li Y, Han Y, Zhu H, Wang Y: Activation of cyclin-dependent kinase 5 (Cdk5) in primary sensory and dorsal horn neurons by peripheral inflammation contributes to heat hyperalgesia. Pain 2007, 127: 109–120. 10.1016/j.pain.2006.08.008CrossRefPubMed Yang YR, He Y, Zhang Y, Li Y, Li Y, Han Y, Zhu H, Wang Y: Activation of cyclin-dependent kinase 5 (Cdk5) in primary sensory and dorsal horn neurons by peripheral inflammation contributes to heat hyperalgesia. Pain 2007, 127: 109–120. 10.1016/j.pain.2006.08.008CrossRefPubMed
32.
go back to reference Pareek TK, Keller J, Kesavapany S, Pant HC, Iadarola MJ, Brady RO, Kulkarni AB: Cyclin-dependent kinase 5 activity regulates pain signaling. Proc Natl Acad Sci USA 2006, 103: 791–796. 10.1073/pnas.0510405103PubMedCentralCrossRefPubMed Pareek TK, Keller J, Kesavapany S, Pant HC, Iadarola MJ, Brady RO, Kulkarni AB: Cyclin-dependent kinase 5 activity regulates pain signaling. Proc Natl Acad Sci USA 2006, 103: 791–796. 10.1073/pnas.0510405103PubMedCentralCrossRefPubMed
33.
go back to reference Maccioni RB, Otth C, Concha II, Munoz JP: The protein kinase Cdk5. Structural aspects, roles in neurogenesis and involvement in Alzheimer’s pathology. Eur J Biochem 2001, 268: 1518–1527. 10.1046/j.1432-1327.2001.02024.xCrossRefPubMed Maccioni RB, Otth C, Concha II, Munoz JP: The protein kinase Cdk5. Structural aspects, roles in neurogenesis and involvement in Alzheimer’s pathology. Eur J Biochem 2001, 268: 1518–1527. 10.1046/j.1432-1327.2001.02024.xCrossRefPubMed
34.
go back to reference Langford DJ, Bailey AL, Chanda ML, Clarke SE, Drummond TE, Echols S, Glick S, Ingrao J, Klassen-Ross T, Lacroix-Fralish ML, et al.: Coding of facial expressions of pain in the laboratory mouse. Nat Methods 2010, 7: 447–449. 10.1038/nmeth.1455CrossRefPubMed Langford DJ, Bailey AL, Chanda ML, Clarke SE, Drummond TE, Echols S, Glick S, Ingrao J, Klassen-Ross T, Lacroix-Fralish ML, et al.: Coding of facial expressions of pain in the laboratory mouse. Nat Methods 2010, 7: 447–449. 10.1038/nmeth.1455CrossRefPubMed
35.
go back to reference Dolan JC, Lam DK, Achdjian SH, Schmidt BL: The dolognawmeter: a novel instrument and assay to quantify nociception in rodent models of orofacial pain. J Neurosci Methods 2010, 187: 207–215. 10.1016/j.jneumeth.2010.01.012PubMedCentralCrossRefPubMed Dolan JC, Lam DK, Achdjian SH, Schmidt BL: The dolognawmeter: a novel instrument and assay to quantify nociception in rodent models of orofacial pain. J Neurosci Methods 2010, 187: 207–215. 10.1016/j.jneumeth.2010.01.012PubMedCentralCrossRefPubMed
36.
go back to reference Ambalavanar R, Moritani M, Dessem D: Trigeminal P2X3 receptor expression differs from dorsal root ganglion and is modulated by deep tissue inflammation. Pain 2005, 117: 280–291. 10.1016/j.pain.2005.06.029CrossRefPubMed Ambalavanar R, Moritani M, Dessem D: Trigeminal P2X3 receptor expression differs from dorsal root ganglion and is modulated by deep tissue inflammation. Pain 2005, 117: 280–291. 10.1016/j.pain.2005.06.029CrossRefPubMed
37.
go back to reference Harriott AM, Gold MS: Serotonin type 1D receptors (5HTR) are differentially distributed in nerve fibres innervating craniofacial tissues. Cephalalgia 2008, 28: 933–944. 10.1111/j.1468-2982.2008.01635.xPubMedCentralCrossRefPubMed Harriott AM, Gold MS: Serotonin type 1D receptors (5HTR) are differentially distributed in nerve fibres innervating craniofacial tissues. Cephalalgia 2008, 28: 933–944. 10.1111/j.1468-2982.2008.01635.xPubMedCentralCrossRefPubMed
38.
go back to reference Harriott AM, Gold MS: Electrophysiological properties of dural afferents in the absence and presence of inflammatory mediators. J Neurophysiol 2009, 101: 3126–3134. 10.1152/jn.91339.2008PubMedCentralCrossRefPubMed Harriott AM, Gold MS: Electrophysiological properties of dural afferents in the absence and presence of inflammatory mediators. J Neurophysiol 2009, 101: 3126–3134. 10.1152/jn.91339.2008PubMedCentralCrossRefPubMed
39.
go back to reference Wang CH, Chou WY, Hung KS, Jawan B, Lu CN, Liu JK, Hung YP, Lee TH: Intrathecal administration of roscovitine inhibits Cdk5 activity and attenuates formalin-induced nociceptive response in rats. Acta Pharmacol Sin 2005, 26: 46–50. 10.1111/j.1745-7254.2005.00007.xCrossRefPubMed Wang CH, Chou WY, Hung KS, Jawan B, Lu CN, Liu JK, Hung YP, Lee TH: Intrathecal administration of roscovitine inhibits Cdk5 activity and attenuates formalin-induced nociceptive response in rats. Acta Pharmacol Sin 2005, 26: 46–50. 10.1111/j.1745-7254.2005.00007.xCrossRefPubMed
40.
go back to reference Caterina MJ, Schumacher MA, Tominaga M, Rosen TA, Levine JD, Julius D: The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature 1997, 389: 816–824. 10.1038/39807CrossRefPubMed Caterina MJ, Schumacher MA, Tominaga M, Rosen TA, Levine JD, Julius D: The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature 1997, 389: 816–824. 10.1038/39807CrossRefPubMed
41.
go back to reference Tominaga M, Caterina MJ, Malmberg AB, Rosen TA, Gilbert H, Skinner K, Raumann BE, Basbaum AI, Julius D: The cloned capsaicin receptor integrates multiple pain-producing stimuli. Neuron 1998, 21: 531–543. 10.1016/S0896-6273(00)80564-4CrossRefPubMed Tominaga M, Caterina MJ, Malmberg AB, Rosen TA, Gilbert H, Skinner K, Raumann BE, Basbaum AI, Julius D: The cloned capsaicin receptor integrates multiple pain-producing stimuli. Neuron 1998, 21: 531–543. 10.1016/S0896-6273(00)80564-4CrossRefPubMed
42.
go back to reference Caterina MJ, Leffler A, Malmberg AB, Martin WJ, Trafton J, Petersen-Zeitz KR, Koltzenburg M, Basbaum AI, Julius D: Impaired nociception and pain sensation in mice lacking the capsaicin receptor. Science 2000, 288: 306–313. 10.1126/science.288.5464.306CrossRefPubMed Caterina MJ, Leffler A, Malmberg AB, Martin WJ, Trafton J, Petersen-Zeitz KR, Koltzenburg M, Basbaum AI, Julius D: Impaired nociception and pain sensation in mice lacking the capsaicin receptor. Science 2000, 288: 306–313. 10.1126/science.288.5464.306CrossRefPubMed
43.
go back to reference Xing BM, Yang YR, Du JX, Chen HJ, Qi C, Huang ZH, Zhang Y, Wang Y: Cyclin-dependent kinase 5 controls TRPV1 membrane trafficking and the heat sensitivity of nociceptors through KIF13B. J Neurosci 2012, 32: 14709–14721. 10.1523/JNEUROSCI.1634-12.2012CrossRefPubMed Xing BM, Yang YR, Du JX, Chen HJ, Qi C, Huang ZH, Zhang Y, Wang Y: Cyclin-dependent kinase 5 controls TRPV1 membrane trafficking and the heat sensitivity of nociceptors through KIF13B. J Neurosci 2012, 32: 14709–14721. 10.1523/JNEUROSCI.1634-12.2012CrossRefPubMed
44.
go back to reference Cui M, Honore P, Zhong C, Gauvin D, Mikusa J, Hernandez G, Chandran P, Gomtsyan A, Brown B, Bayburt EK, et al.: TRPV1 receptors in the CNS play a key role in broad-spectrum analgesia of TRPV1 antagonists. J Neurosci 2006, 26: 9385–9393. 10.1523/JNEUROSCI.1246-06.2006CrossRefPubMed Cui M, Honore P, Zhong C, Gauvin D, Mikusa J, Hernandez G, Chandran P, Gomtsyan A, Brown B, Bayburt EK, et al.: TRPV1 receptors in the CNS play a key role in broad-spectrum analgesia of TRPV1 antagonists. J Neurosci 2006, 26: 9385–9393. 10.1523/JNEUROSCI.1246-06.2006CrossRefPubMed
45.
go back to reference Watabiki T, Kiso T, Tsukamoto M, Aoki T, Matsuoka N: Intrathecal administration of AS1928370, a transient receptor potential vanilloid 1 antagonist, attenuates mechanical allodynia in a mouse model of neuropathic pain. Biol Pharm Bull 2011, 34: 1105–1108. 10.1248/bpb.34.1105CrossRefPubMed Watabiki T, Kiso T, Tsukamoto M, Aoki T, Matsuoka N: Intrathecal administration of AS1928370, a transient receptor potential vanilloid 1 antagonist, attenuates mechanical allodynia in a mouse model of neuropathic pain. Biol Pharm Bull 2011, 34: 1105–1108. 10.1248/bpb.34.1105CrossRefPubMed
46.
go back to reference Yu L, Yang F, Luo H, Liu FY, Han JS, Xing GG, Wan Y: The role of TRPV1 in different subtypes of dorsal root ganglion neurons in rat chronic inflammatory nociception induced by complete Freund’s adjuvant. Mol Pain 2008, 4: 61. 10.1186/1744-8069-4-61PubMedCentralCrossRefPubMed Yu L, Yang F, Luo H, Liu FY, Han JS, Xing GG, Wan Y: The role of TRPV1 in different subtypes of dorsal root ganglion neurons in rat chronic inflammatory nociception induced by complete Freund’s adjuvant. Mol Pain 2008, 4: 61. 10.1186/1744-8069-4-61PubMedCentralCrossRefPubMed
47.
go back to reference Ro JY, Lee JS, Zhang Y: Activation of TRPV1 and TRPA1 leads to muscle nociception and mechanical hyperalgesia. Pain 2009, 144: 270–277. 10.1016/j.pain.2009.04.021PubMedCentralCrossRefPubMed Ro JY, Lee JS, Zhang Y: Activation of TRPV1 and TRPA1 leads to muscle nociception and mechanical hyperalgesia. Pain 2009, 144: 270–277. 10.1016/j.pain.2009.04.021PubMedCentralCrossRefPubMed
48.
go back to reference Saloman JL, Chung MK, Ro JY: P2X (3) and TRPV1 functionally interact and mediate sensitization of trigeminal sensory neurons. Neuroscience 2012, 232: 226–238.CrossRefPubMed Saloman JL, Chung MK, Ro JY: P2X (3) and TRPV1 functionally interact and mediate sensitization of trigeminal sensory neurons. Neuroscience 2012, 232: 226–238.CrossRefPubMed
49.
go back to reference Lee J, Saloman JL, Weiland G, Auh QS, Chung MK, Ro JY: Functional interactions between NMDA receptors and TRPV1 in trigeminal sensory neurons mediate mechanical hyperalgesia in the rat masseter muscle. Pain 2012, 153: 1514–1524. 10.1016/j.pain.2012.04.015PubMedCentralCrossRefPubMed Lee J, Saloman JL, Weiland G, Auh QS, Chung MK, Ro JY: Functional interactions between NMDA receptors and TRPV1 in trigeminal sensory neurons mediate mechanical hyperalgesia in the rat masseter muscle. Pain 2012, 153: 1514–1524. 10.1016/j.pain.2012.04.015PubMedCentralCrossRefPubMed
50.
51.
go back to reference Kim SH, Ryan TA: Balance of calcineurin aalpha and CDK5 activities sets release probability at nerve terminals. J Neurosci 2013, 33: 8937–8950. 10.1523/JNEUROSCI.4288-12.2013CrossRefPubMed Kim SH, Ryan TA: Balance of calcineurin aalpha and CDK5 activities sets release probability at nerve terminals. J Neurosci 2013, 33: 8937–8950. 10.1523/JNEUROSCI.4288-12.2013CrossRefPubMed
52.
go back to reference Zhang HH, Zhang XQ, Wang WY, Xue QS, Lu H, Huang JL, Gui T, Yu BW: Increased synaptophysin is involved in inflammation-induced heat hyperalgesia mediated by cyclin-dependent kinase 5 in rats. PLoS One 2012, 7: e46666. 10.1371/journal.pone.0046666PubMedCentralCrossRefPubMed Zhang HH, Zhang XQ, Wang WY, Xue QS, Lu H, Huang JL, Gui T, Yu BW: Increased synaptophysin is involved in inflammation-induced heat hyperalgesia mediated by cyclin-dependent kinase 5 in rats. PLoS One 2012, 7: e46666. 10.1371/journal.pone.0046666PubMedCentralCrossRefPubMed
53.
go back to reference Chen HJ, Xie WY, Hu F, Zhang Y, Wang J, Wang Y: Disruption of delta-opioid receptor phosphorylation at threonine 161 attenuates morphine tolerance in rats with CFA-induced inflammatory hypersensitivity. Neurosci Bull 2012, 28: 182–192. 10.1007/s12264-012-1216-8CrossRefPubMed Chen HJ, Xie WY, Hu F, Zhang Y, Wang J, Wang Y: Disruption of delta-opioid receptor phosphorylation at threonine 161 attenuates morphine tolerance in rats with CFA-induced inflammatory hypersensitivity. Neurosci Bull 2012, 28: 182–192. 10.1007/s12264-012-1216-8CrossRefPubMed
54.
go back to reference Xie WY, He Y, Yang YR, Li YF, Kang K, Xing BM, Wang Y: Disruption of Cdk5-associated phosphorylation of residue threonine-161 of the delta-opioid receptor: impaired receptor function and attenuated morphine antinociceptive tolerance. J Neurosci 2009, 29: 3551–3564. 10.1523/JNEUROSCI.0415-09.2009CrossRefPubMed Xie WY, He Y, Yang YR, Li YF, Kang K, Xing BM, Wang Y: Disruption of Cdk5-associated phosphorylation of residue threonine-161 of the delta-opioid receptor: impaired receptor function and attenuated morphine antinociceptive tolerance. J Neurosci 2009, 29: 3551–3564. 10.1523/JNEUROSCI.0415-09.2009CrossRefPubMed
55.
go back to reference Zhang R, Liu Y, Zhang J, Zheng Y, Gu X, Ma Z: Intrathecal administration of roscovitine attenuates cancer pain and inhibits the expression of NMDA receptor 2B subunit mRNA. Pharmacol Biochem Behav 2012, 102: 139–145. 10.1016/j.pbb.2012.03.025CrossRefPubMed Zhang R, Liu Y, Zhang J, Zheng Y, Gu X, Ma Z: Intrathecal administration of roscovitine attenuates cancer pain and inhibits the expression of NMDA receptor 2B subunit mRNA. Pharmacol Biochem Behav 2012, 102: 139–145. 10.1016/j.pbb.2012.03.025CrossRefPubMed
56.
go back to reference Zhang S, Edelmann L, Liu J, Crandall JE, Morabito MA: Cdk5 regulates the phosphorylation of tyrosine 1472 NR2B and the surface expression of NMDA receptors. J Neurosci 2008, 28: 415–424. 10.1523/JNEUROSCI.1900-07.2008CrossRefPubMed Zhang S, Edelmann L, Liu J, Crandall JE, Morabito MA: Cdk5 regulates the phosphorylation of tyrosine 1472 NR2B and the surface expression of NMDA receptors. J Neurosci 2008, 28: 415–424. 10.1523/JNEUROSCI.1900-07.2008CrossRefPubMed
57.
go back to reference Nair A, Simonetti M, Fabbretti E, Nistri A: The Cdk5 kinase downregulates ATP-gated ionotropic P2X3 receptor function via serine phosphorylation. Cell Mol Neurobiol 2010, 30: 505–509. 10.1007/s10571-009-9483-2CrossRefPubMed Nair A, Simonetti M, Fabbretti E, Nistri A: The Cdk5 kinase downregulates ATP-gated ionotropic P2X3 receptor function via serine phosphorylation. Cell Mol Neurobiol 2010, 30: 505–509. 10.1007/s10571-009-9483-2CrossRefPubMed
58.
go back to reference Tomizawa K, Ohta J, Matsushita M, Moriwaki A, Li ST, Takei K, Matsui H: Cdk5/p35 regulates neurotransmitter release through phosphorylation and downregulation of P/Q-type voltage-dependent calcium channel activity. J Neurosci 2002, 22: 2590–2597.PubMed Tomizawa K, Ohta J, Matsushita M, Moriwaki A, Li ST, Takei K, Matsui H: Cdk5/p35 regulates neurotransmitter release through phosphorylation and downregulation of P/Q-type voltage-dependent calcium channel activity. J Neurosci 2002, 22: 2590–2597.PubMed
59.
go back to reference Brierley SM, Castro J, Harrington AM, Hughes PA, Page AJ, Rychkov GY, Blackshaw LA: TRPA1 contributes to specific mechanically activated currents and sensory neuron mechanical hypersensitivity. J Physiol 2011, 589: 3575–3593. 10.1113/jphysiol.2011.206789PubMedCentralCrossRefPubMed Brierley SM, Castro J, Harrington AM, Hughes PA, Page AJ, Rychkov GY, Blackshaw LA: TRPA1 contributes to specific mechanically activated currents and sensory neuron mechanical hypersensitivity. J Physiol 2011, 589: 3575–3593. 10.1113/jphysiol.2011.206789PubMedCentralCrossRefPubMed
60.
go back to reference Brierley SM, Hughes PA, Page AJ, Kwan KY, Martin CM, O’Donnell TA, Cooper NJ, Harrington AM, Adam B, Liebregts T, et al.: The ion channel TRPA1 is required for normal mechanosensation and is modulated by algesic stimuli. Gastroenterology 2009, 137: 2084–2095. e2083 10.1053/j.gastro.2009.07.048PubMedCentralCrossRefPubMed Brierley SM, Hughes PA, Page AJ, Kwan KY, Martin CM, O’Donnell TA, Cooper NJ, Harrington AM, Adam B, Liebregts T, et al.: The ion channel TRPA1 is required for normal mechanosensation and is modulated by algesic stimuli. Gastroenterology 2009, 137: 2084–2095. e2083 10.1053/j.gastro.2009.07.048PubMedCentralCrossRefPubMed
61.
go back to reference Kwan KY, Glazer JM, Corey DP, Rice FL, Stucky CL: TRPA1 modulates mechanotransduction in cutaneous sensory neurons. J Neurosci 2009, 29: 4808–4819. 10.1523/JNEUROSCI.5380-08.2009PubMedCentralCrossRefPubMed Kwan KY, Glazer JM, Corey DP, Rice FL, Stucky CL: TRPA1 modulates mechanotransduction in cutaneous sensory neurons. J Neurosci 2009, 29: 4808–4819. 10.1523/JNEUROSCI.5380-08.2009PubMedCentralCrossRefPubMed
62.
go back to reference Alloui A, Zimmermann K, Mamet J, Duprat F, Noel J, Chemin J, Guy N, Blondeau N, Voilley N, Rubat-Coudert C, et al.: TREK-1, a K + channel involved in polymodal pain perception. EMBO J 2006, 25: 2368–2376. 10.1038/sj.emboj.7601116PubMedCentralCrossRefPubMed Alloui A, Zimmermann K, Mamet J, Duprat F, Noel J, Chemin J, Guy N, Blondeau N, Voilley N, Rubat-Coudert C, et al.: TREK-1, a K + channel involved in polymodal pain perception. EMBO J 2006, 25: 2368–2376. 10.1038/sj.emboj.7601116PubMedCentralCrossRefPubMed
63.
go back to reference Dedman A, Sharif-Naeini R, Folgering JH, Duprat F, Patel A, Honore E: The mechano-gated K (2P) channel TREK-1. Eur Biophys J 2009, 38: 293–303. 10.1007/s00249-008-0318-8CrossRefPubMed Dedman A, Sharif-Naeini R, Folgering JH, Duprat F, Patel A, Honore E: The mechano-gated K (2P) channel TREK-1. Eur Biophys J 2009, 38: 293–303. 10.1007/s00249-008-0318-8CrossRefPubMed
64.
go back to reference Zimmermann M: Ethical guidelines for investigations of experimental pain in conscious animals. Pain 1983, 16: 109–110. 10.1016/0304-3959(83)90201-4CrossRefPubMed Zimmermann M: Ethical guidelines for investigations of experimental pain in conscious animals. Pain 1983, 16: 109–110. 10.1016/0304-3959(83)90201-4CrossRefPubMed
65.
go back to reference Nolan TA, Caudle RM, Neubert JK: Effect of caloric and non-caloric sweet reward solutions on thermal facial operant conditioning. Behav Brain Res 2011, 216: 723–725. 10.1016/j.bbr.2010.08.023PubMedCentralCrossRefPubMed Nolan TA, Caudle RM, Neubert JK: Effect of caloric and non-caloric sweet reward solutions on thermal facial operant conditioning. Behav Brain Res 2011, 216: 723–725. 10.1016/j.bbr.2010.08.023PubMedCentralCrossRefPubMed
66.
go back to reference Veeranna A, Shetty KT, Amin N, Grant P, Albers RW, Pant HC: Inhibition of neuronal cyclin-dependent kinase-5 by staurosporine and purine analogs is independent of activation by Munc-18. Neurochem Res 1996, 21: 629–636. 10.1007/BF02527763CrossRefPubMed Veeranna A, Shetty KT, Amin N, Grant P, Albers RW, Pant HC: Inhibition of neuronal cyclin-dependent kinase-5 by staurosporine and purine analogs is independent of activation by Munc-18. Neurochem Res 1996, 21: 629–636. 10.1007/BF02527763CrossRefPubMed
Metadata
Title
Activation of cyclin-dependent kinase 5 mediates orofacial mechanical hyperalgesia
Authors
Michaela Prochazkova
Anita Terse
Niranjana D Amin
Bradford Hall
Elias Utreras
Harish C Pant
Ashok B Kulkarni
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Molecular Pain / Issue 1/2013
Electronic ISSN: 1744-8069
DOI
https://doi.org/10.1186/1744-8069-9-66

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Reviewer acknowledgement