Neuropathic Pain Dysregulates Gene Expression of the Forebrain Opioid and Dopamine Systems.
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.
['Wawrzczak-Bargieła|Agnieszka|A|https://orcid.org/0000-0002-9051-8369', 'Ziółkowska|Barbara|B|https://orcid.org/0000-0002-6782-7737', 'Piotrowska|Anna|A|https://orcid.org/0000-0002-2091-2678', 'Starnowska-Sokół|Joanna|J|', 'Rojewska|Ewelina|E|https://orcid.org/0000-0001-8383-7356', 'Mika|Joanna|J|https://orcid.org/0000-0003-1986-7205', 'Przewłocka|Barbara|B|https://orcid.org/0000-0002-6672-1906', 'Przewłocki|Ryszard|R|https://orcid.org/0000-0003-4606-1629']
D000818:Animals D003342:Corpus Striatum D004745:Enkephalins D015870:Gene Expression D008297:Male D051379:Mice D009437:Neuralgia D010147:Pain Measurement D016548:Prosencephalon D011498:Protein Precursors D011954:Receptors, Dopamine D017465:Receptors, Opioid, delta D017473:Receptors, Opioid, kappa D017450:Receptors, Opioid, mu
Opioids Dopamine Chronic pain Mesostriatal system Nucleus accumbens Neuropathy