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Which comes first, neuroimmunity or Mu-Opioid receptors? A pivotal relationship to unravel pain-induced alcohol relapse

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Which comes first, neuroimmunity or Mu-Opioid receptors? A pivotal relationship to unravel pain-induced alcohol relapse

dc.contributor.advisor	Hipólito Cubedo, Lucía Teresa
dc.contributor.advisor	Polache Vengut, Ana
dc.contributor.advisor	Agustín Pavón, María Carmen
dc.contributor.author	Cuitavi Martín, Javier
dc.contributor.other	Departament de Farmàcia i Tecnologia Farmacèutica	es_ES
dc.date.accessioned	2023-07-30T14:22:19Z
dc.date.available	2023-07-31T04:45:06Z
dc.date.issued	2023	es_ES
dc.date.submitted	26-07-2023	es_ES
dc.identifier.uri	https://hdl.handle.net/10550/88829
dc.description.abstract	The relapse phenomenon occurs due to several factors such as stress, drug associated cues and, as it has been recently suggested, pain. However, the underlying biochemical changes that underlie relapse due to pain suffering have not been described yet. Furthermore, Mu Opioid Receptors (MOR) in the mesocorticolimbic system (MCLS) but also neuroimmune processes play a key role in alcohol addiction and relapse. Additionally, some studies have revealed that MORs might be related to neuroinflammatory processes which are activated after ethanol exposure. However, the way in which neuroinflammation is related with MORs expression and function is still not fully understood. In this sense, the general aim of the present doctoral thesis is to study the relationship between MORs and the immune system and to investigate how this relationship plays a role in pain-induced alcohol use disorders. To test this hypothesis, we used a combination of in vivo and in vitro techniques: microdialysis, flow cytometry, western blot, immunohistochemistry, behavioural tests, neuropharmacology, cell cultures, and bioluminescence resonance energy transfer. In general our results indicate the MOR activation accounts for microgliosis and the release of proinflammatory cytokines, which in turn seems to modulate neuronal MOR signalling and expression. Moreover, pain modifies MOR-derived inflammation, which suggests a newly described mechanism by which pain might affect alcohol relapse-like behaviours. Thus we conclude: # Conclusion 1. MORs activation in the MCLS induces proinflammatory cytokines release and microgliosis within the system. # Conclusion 2. Inflammatory pain alters microglial proliferation in areas of the MCLS. # Conclusion 3. Inflammatory pain irrupts in the neuroinflammation triggered by MOR activation within the MCLS. # Conclusion 4. Microglial activation induces neuronal MOR activation and expression through proinflammatory cytokines signalling. # Conclusion 5. MOR activation-induced neuroinflammation leads to an increase in neuronal MOR expression and signalling. # Conclusion 6. Inflammatory pain induces alcohol relapse only in female rats. # Conclusion 7. The levels of microglial cells, IL1β, and MORs correlate in females suffering from inflammatory pain in an alcohol deprivation effect model suggesting that their all implicated in pain-induced alcohol relapse in female rats.	es_ES
dc.format.extent	224 p.	es_ES
dc.language.iso	en	es_ES
dc.subject	neuroimmunity	es_ES
dc.subject	mu-opioid receptor	es_ES
dc.subject	pain	es_ES
dc.subject	alcohol	es_ES
dc.title	Which comes first, neuroimmunity or Mu-Opioid receptors? A pivotal relationship to unravel pain-induced alcohol relapse	es_ES
dc.type	doctoral thesis	es_ES
dc.subject.unesco	UNESCO::CIENCIAS MÉDICAS ::Farmacología	es_ES
dc.subject.unesco	UNESCO::CIENCIAS DE LA VIDA::Inmunología	es_ES
dc.subject.unesco	UNESCO::CIENCIAS DE LA VIDA::Neurociencias	es_ES
dc.embargo.terms	0 days	es_ES
dc.rights.accessRights	open access	es_ES