Neuropathic Pain Dysregulates Gene Expression of the Forebrain Opioid and Dopamine Systems

Overview

Journal Neurotox Res

Publisher Springer

Specialty Neurology

Date 2020 Feb 7

PMID 32026358

Citations 17

Authors

Agnieszka Wawrzczak-Bargiela

Barbara Ziolkowska

Anna Piotrowska

Joanna Starnowska-Sokol

Ewelina Rojewska

Joanna Mika

Barbara Przewlocka

Ryszard Przewlocki

Affiliations

Soon will be listed here.

Abstract

Disturbances in the function of the mesostriatal dopamine system may contribute to the development and maintenance of chronic pain, including its sensory and emotional/cognitive aspects. In the present study, we assessed the influence of chronic constriction injury (CCI) of the sciatic nerve on the expression of genes coding for dopamine and opioid receptors as well as opioid propeptides in the mouse mesostriatal system, particularly in the nucleus accumbens. We demonstrated bilateral increases in mRNA levels of the dopamine D1 and D2 receptors (the latter accompanied by elevated protein level), opioid propeptides proenkephalin and prodynorphin, as well as delta and kappa (but not mu) opioid receptors in the nucleus accumbens at 7 to 14 days after CCI. These results show that CCI-induced neuropathic pain is accompanied by a major transcriptional dysregulation of molecules involved in dopaminergic and opioidergic signaling in the striatum/nucleus accumbens. Possible functional consequences of these changes include opposite effects of upregulated enkephalin/delta opioid receptor signaling vs. dynorphin/kappa opioid receptor signaling, with the former most likely having an analgesic effect and the latter exacerbating pain and contributing to pain-related negative emotional states.

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References

Tejeda H, Wu J, Kornspun A, Pignatelli M, Kashtelyan V, Krashes M . Pathway- and Cell-Specific Kappa-Opioid Receptor Modulation of Excitation-Inhibition Balance Differentially Gates D1 and D2 Accumbens Neuron Activity. Neuron. 2017; 93(1):147-163. PMC: 5808882. DOI: 10.1016/j.neuron.2016.12.005. View

Llorca-Torralba M, Pilar-Cuellar F, da Silva Borges G, Mico J, Berrocoso E . Opioid receptors mRNAs expression and opioids agonist-dependent G-protein activation in the rat brain following neuropathy. Prog Neuropsychopharmacol Biol Psychiatry. 2020; 99:109857. DOI: 10.1016/j.pnpbp.2019.109857. View

Ren W, Centeno M, Berger S, Wu Y, Na X, Liu X . The indirect pathway of the nucleus accumbens shell amplifies neuropathic pain. Nat Neurosci. 2015; 19(2):220-2. PMC: 4889808. DOI: 10.1038/nn.4199. View

Steiner H, Gerfen C . Enkephalin regulates acute D2 dopamine receptor antagonist-induced immediate-early gene expression in striatal neurons. Neuroscience. 1999; 88(3):795-810. DOI: 10.1016/s0306-4522(98)00241-3. View

Oude Ophuis R, Boender A, Van Rozen A, Adan R . Cannabinoid, melanocortin and opioid receptor expression on DRD1 and DRD2 subpopulations in rat striatum. Front Neuroanat. 2014; 8:14. PMC: 3972466. DOI: 10.3389/fnana.2014.00014. View

Herz A, Shippenberg T . Evidence that the aversive effects of opioid antagonists and kappa-agonists are centrally mediated. Psychopharmacology (Berl). 1989; 98(2):203-6. DOI: 10.1007/BF00444692. View

Gerfen C, Engber T, Mahan L, Susel Z, Chase T, Monsma Jr F . D1 and D2 dopamine receptor-regulated gene expression of striatonigral and striatopallidal neurons. Science. 1990; 250(4986):1429-32. DOI: 10.1126/science.2147780. View

Anagnostakis Y, Zis V, Spyraki C . Analgesia induced by morphine injected into the pallidum. Behav Brain Res. 1992; 48(2):135-43. DOI: 10.1016/s0166-4328(05)80149-4. View

Spanagel R, Herz A, Shippenberg T . Opposing tonically active endogenous opioid systems modulate the mesolimbic dopaminergic pathway. Proc Natl Acad Sci U S A. 1992; 89(6):2046-50. PMC: 48593. DOI: 10.1073/pnas.89.6.2046. View

10.

Ghasemzadeh M, Sharma S, Surmeier D, Eberwine J, Chesselet M . Multiplicity of glutamate receptor subunits in single striatal neurons: an RNA amplification study. Mol Pharmacol. 1996; 49(5):852-9. View

11.

Gerfen C, Surmeier D . Modulation of striatal projection systems by dopamine. Annu Rev Neurosci. 2011; 34:441-66. PMC: 3487690. DOI: 10.1146/annurev-neuro-061010-113641. View

12.

Mika J, Jurga A, Starnowska J, Wasylewski M, Rojewska E, Makuch W . Effects of chronic doxepin and amitriptyline administration in naïve mice and in neuropathic pain mice model. Neuroscience. 2015; 294:38-50. DOI: 10.1016/j.neuroscience.2015.03.003. View

13.

Massaly N, Copits B, Wilson-Poe A, Hipolito L, Markovic T, Yoon H . Pain-Induced Negative Affect Is Mediated via Recruitment of The Nucleus Accumbens Kappa Opioid System. Neuron. 2019; 102(3):564-573.e6. PMC: 6509001. DOI: 10.1016/j.neuron.2019.02.029. View

14.

Zhou L, Furuta T, Kaneko T . Chemical organization of projection neurons in the rat accumbens nucleus and olfactory tubercle. Neuroscience. 2003; 120(3):783-98. DOI: 10.1016/s0306-4522(03)00326-9. View

15.

Ozaki S, Narita M, Narita M, Iino M, Sugita J, Matsumura Y . Suppression of the morphine-induced rewarding effect in the rat with neuropathic pain: implication of the reduction in mu-opioid receptor functions in the ventral tegmental area. J Neurochem. 2002; 82(5):1192-8. DOI: 10.1046/j.1471-4159.2002.01071.x. View

16.

Suzuki T, Kishimoto Y, Misawa M, Nagase H, Takeda F . Role of the kappa-opioid system in the attenuation of the morphine-induced place preference under chronic pain. Life Sci. 1999; 64(1):PL1-7. DOI: 10.1016/s0024-3205(98)00537-2. View

17.

Su C, Damour J, Lee M, Lin H, Manders T, Xu D . Persistent pain alters AMPA receptor subunit levels in the nucleus accumbens. Mol Brain. 2015; 8:46. PMC: 4531890. DOI: 10.1186/s13041-015-0140-z. View

18.

Breivik H, Collett B, Ventafridda V, Cohen R, Gallacher D . Survey of chronic pain in Europe: prevalence, impact on daily life, and treatment. Eur J Pain. 2005; 10(4):287-333. DOI: 10.1016/j.ejpain.2005.06.009. View

19.

Brischoux F, Chakraborty S, Brierley D, Ungless M . Phasic excitation of dopamine neurons in ventral VTA by noxious stimuli. Proc Natl Acad Sci U S A. 2009; 106(12):4894-9. PMC: 2660746. DOI: 10.1073/pnas.0811507106. View

20.

Geha P, Baliki M, Harden R, Bauer W, Parrish T, Apkarian A . The brain in chronic CRPS pain: abnormal gray-white matter interactions in emotional and autonomic regions. Neuron. 2008; 60(4):570-81. PMC: 2637446. DOI: 10.1016/j.neuron.2008.08.022. View