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Balancing GRK2 and EPAC1 levels prevents and relieves chronic pain.

Wang H, Heijnen CJ, van Velthoven CT, Willemen HL, Ishikawa Y, Zhang X, Sood AK, Vroon A, Eijkelkamp N, Kavelaars A.

J Clin Invest. 2013 Dec;123(12):5023-34. doi: 10.1172/JCI66241.


Critical role for Epac1 in inflammatory pain controlled by GRK2-mediated phosphorylation of Epac1.

Singhmar P, Huo X, Eijkelkamp N, Berciano SR, Baameur F, Mei FC, Zhu Y, Cheng X, Hawke D, Mayor F Jr, Murga C, Heijnen CJ, Kavelaars A.

Proc Natl Acad Sci U S A. 2016 Mar 15;113(11):3036-41. doi: 10.1073/pnas.1516036113.


Low nociceptor GRK2 prolongs prostaglandin E2 hyperalgesia via biased cAMP signaling to Epac/Rap1, protein kinase Cepsilon, and MEK/ERK.

Eijkelkamp N, Wang H, Garza-Carbajal A, Willemen HL, Zwartkruis FJ, Wood JN, Dantzer R, Kelley KW, Heijnen CJ, Kavelaars A.

J Neurosci. 2010 Sep 22;30(38):12806-15. doi: 10.1523/JNEUROSCI.3142-10.2010.


GRK2: a novel cell-specific regulator of severity and duration of inflammatory pain.

Eijkelkamp N, Heijnen CJ, Willemen HL, Deumens R, Joosten EA, Kleibeuker W, den Hartog IJ, van Velthoven CT, Nijboer C, Nassar MA, Dorn GW 2nd, Wood JN, Kavelaars A.

J Neurosci. 2010 Feb 10;30(6):2138-49. doi: 10.1523/JNEUROSCI.5752-09.2010.


Hyperalgesic priming is restricted to isolectin B4-positive nociceptors.

Joseph EK, Levine JD.

Neuroscience. 2010 Aug 11;169(1):431-5. doi: 10.1016/j.neuroscience.2010.04.082.


Transient decrease in nociceptor GRK2 expression produces long-term enhancement in inflammatory pain.

Ferrari LF, Bogen O, Alessandri-Haber N, Levine E, Gear RW, Levine JD.

Neuroscience. 2012 Oct 11;222:392-403. doi: 10.1016/j.neuroscience.2012.07.004.


GRK2 in sensory neurons regulates epinephrine-induced signalling and duration of mechanical hyperalgesia.

Wang H, Heijnen CJ, Eijkelkamp N, Garza Carbajal A, Schedlowski M, Kelley KW, Dantzer R, Kavelaars A.

Pain. 2011 Jul;152(7):1649-58. doi: 10.1016/j.pain.2011.03.010.


MicroRNA-124 as a novel treatment for persistent hyperalgesia.

Willemen HL, Huo XJ, Mao-Ying QL, Zijlstra J, Heijnen CJ, Kavelaars A.

J Neuroinflammation. 2012 Jun 25;9:143. doi: 10.1186/1742-2094-9-143.


Microglial/macrophage GRK2 determines duration of peripheral IL-1beta-induced hyperalgesia: contribution of spinal cord CX3CR1, p38 and IL-1 signaling.

Willemen HL, Eijkelkamp N, Wang H, Dantzer R, Dorn GW 2nd, Kelley KW, Heijnen CJ, Kavelaars A.

Pain. 2010 Sep;150(3):550-60. doi: 10.1016/j.pain.2010.06.015.


Monocytes/Macrophages control resolution of transient inflammatory pain.

Willemen HL, Eijkelkamp N, Garza Carbajal A, Wang H, Mack M, Zijlstra J, Heijnen CJ, Kavelaars A.

J Pain. 2014 May;15(5):496-506. doi: 10.1016/j.jpain.2014.01.491.


Microglial GRK2: a novel regulator of transition from acute to chronic pain.

Kavelaars A, Eijkelkamp N, Willemen HL, Wang H, Carbajal AG, Heijnen CJ.

Brain Behav Immun. 2011 Aug;25(6):1055-60. doi: 10.1016/j.bbi.2011.03.019.


Distinct terminal and cell body mechanisms in the nociceptor mediate hyperalgesic priming.

Ferrari LF, Araldi D, Levine JD.

J Neurosci. 2015 Apr 15;35(15):6107-16. doi: 10.1523/JNEUROSCI.5085-14.2015.


Chronic hyperalgesic priming in the rat involves a novel interaction between cAMP and PKCepsilon second messenger pathways.

Parada CA, Reichling DB, Levine JD.

Pain. 2005 Jan;113(1-2):185-90. Erratum in: Pain. 2005 May;115(1-2):223.


Accounting for the delay in the transition from acute to chronic pain: axonal and nuclear mechanisms.

Ferrari LF, Bogen O, Reichling DB, Levine JD.

J Neurosci. 2015 Jan 14;35(2):495-507. doi: 10.1523/JNEUROSCI.5147-13.2015.


A role for Piezo2 in EPAC1-dependent mechanical allodynia.

Eijkelkamp N, Linley JE, Torres JM, Bee L, Dickenson AH, Gringhuis M, Minett MS, Hong GS, Lee E, Oh U, Ishikawa Y, Zwartkuis FJ, Cox JJ, Wood JN.

Nat Commun. 2013;4:1682. doi: 10.1038/ncomms2673.


Role of a novel nociceptor autocrine mechanism in chronic pain.

Ferrari LF, Levine E, Levine JD.

Eur J Neurosci. 2013 May;37(10):1705-13. doi: 10.1111/ejn.12145.


Nitric oxide signaling in pain and nociceptor sensitization in the rat.

Aley KO, McCarter G, Levine JD.

J Neurosci. 1998 Sep 1;18(17):7008-14.


Second messengers mediating the expression of neuroplasticity in a model of chronic pain in the rat.

Ferrari LF, Bogen O, Levine JD.

J Pain. 2014 Mar;15(3):312-20. doi: 10.1016/j.jpain.2013.12.005.


Nerve growth factor mediates a switch in intracellular signaling for PGE2-induced sensitization of sensory neurons from protein kinase A to Epac.

Vasko MR, Habashy Malty R, Guo C, Duarte DB, Zhang Y, Nicol GD.

PLoS One. 2014 Aug 15;9(8):e104529. doi: 10.1371/journal.pone.0104529.

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