GIUV2023-566
The opioid overdose crisis in the United States (USA) from the late 1990s to the present is well known. Its seriousness is such that it has been defined as a priority among the health problems of the American population by the Senate and the US health authorities. Several studies point to the increase in opioid prescriptions for the treatment of non-cancerous painful pathologies as the beginning of this crisis (www.wonder/CDC.gov). In fact, the presence of pain has been revealed to be a major factor in the development of OUD and other drugs such as alcohol, both in clinical and preclinical studies, contrary to previous beliefs based on the few existing studies on this subject until just over 5 years ago. A different situation occurs in Spain, where health control over the prescription of opioids makes it difficult to access these drugs. However, there is free access to another drug that, like opioid drugs, also activates Mu-type opioid receptors (MORs): alcohol. Alcohol is still the most consumed psychoactive substance in Spain. As shown in the AGES 19-20 report published by the National Drug Plan, 77.2% of the population consumes alcohol and 20% of the population consumes it in...The opioid overdose crisis in the United States (USA) from the late 1990s to the present is well known. Its seriousness is such that it has been defined as a priority among the health problems of the American population by the Senate and the US health authorities. Several studies point to the increase in opioid prescriptions for the treatment of non-cancerous painful pathologies as the beginning of this crisis (www.wonder/CDC.gov). In fact, the presence of pain has been revealed to be a major factor in the development of OUD and other drugs such as alcohol, both in clinical and preclinical studies, contrary to previous beliefs based on the few existing studies on this subject until just over 5 years ago. A different situation occurs in Spain, where health control over the prescription of opioids makes it difficult to access these drugs. However, there is free access to another drug that, like opioid drugs, also activates Mu-type opioid receptors (MORs): alcohol. Alcohol is still the most consumed psychoactive substance in Spain. As shown in the AGES 19-20 report published by the National Drug Plan, 77.2% of the population consumes alcohol and 20% of the population consumes it in the form of binge drinking. Alcohol consumption is often motivated by negative emotional situations, with these being the beginning of the development of, or relapse into, alcohol use disorder (AUD). Thus, situations such as chronic pain could be a trigger for relapses or an initiator in compulsive alcohol consumption. Chronic pain affects 17% of the Spanish population, with a very negative impact on the patient's quality of life. Chronic pain is usually accompanied by affective and emotional pathologies such as anxiety, stress and depression, which are especially difficult to treat and are situations that can lead to the use of drugs, including alcohol and opioids, with the idea of self-medicating these negative emotional situations. Pain and reward are opposing processes that, curiously, share the brain structures that process them. In fact, important analogies can be found between the changes generated by pain and drugs of abuse (including alcohol) in key neural elements of the mesolimbic dopaminergic (MLDA) system. These changes could potentially accelerate the escalation of or relapse into drug use. Indeed, data obtained recently in humans and data obtained by our research group in experimental animals show that pain negatively impacts the processing of motivation and reward by altering the functionality of the MDLA system. This system is responsible for the processing and expression of motivated behaviours and learning encouraged by the presence of positive (whether natural or drug) and negative reinforcement. As a consequence of the persistent effects of pain on the MLDA system, we can not only expect negative effects on patients' quality of life (causing anxiety, stress, anhedonia and negative affective states) but it could also have a crucial effect on their vulnerability to suffering an addictive disorder. In this context, the endogenous opioid system is especially relevant, since in addition to being involved in endogenous analgesic mechanisms, it has a key role in controlling the activity of dopaminergic neurons in the MLDA system. Based on this evidence, Doreal's main aim is the study of pain-induced alterations in both sexes on the MLDA system, as well as their impact on emotional states and motivated behaviours, including drug use, in order to develop new personalised therapies.
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- Analizar las bases neurobiologicas de las comorbilidades del dolor cronico
- Estudiar los mecanismos neurobiologicos subyacentes a la recaida en el consumo de alcohol y otras drogas
- Analizar los mecanismos moleculares que relacionan la neuroinflamacion con los receptores opioides en el sistema mesocorticolimbico
- Diseño y desarrollo de nuevas formas farmaceuticas dirigidas a cerebro para el tratamiento de comorbilidades del dolor y/o la adiccion
- Pain comorbidities.Use of animal models and human studies to analyse the alterations to the opioid system induced by the presence of inflammatory pain in key areas of the mesocorticolimbic system and its effect on motivated behaviour and negative affective states.
- Alcoholism relapse.We study the alterations induced by relapse precipitating factors (stress, loneliness) on the endogenous opioid system in cortical and limbic areas during abstinence and relapse in order to advance knowledge for the development of new anti-relapse therapies.
- crosstalk neuroinflammation and opioid receptors.Analysis of the possible bidirectional interaction between mu-opioid receptor signalling and neuroinflammatory processes at both central and peripheral levels. If confirmed, it would open up new therapeutic possibilities in the treatment of pain and drug use disorders.
- Drug delivery systems for brain targeting.Design, development and optimisation of nanometric formulations (liposomes and extracellular vesicles) of the pharmacological agents detected as possible therapies in the previous lines, to be administrated through the nose-to-brain pathway.
| Name | Nature of participation | Entity | Description |
|---|---|---|---|
| LUCIA TERESA HIPOLITO CUBEDO | Director | Universitat de València | |
| Research team | |||
| JESUS DAVID LORENTE ERENAS | Collaborator | Universitat de València - Estudi General | UVEG PhD student |
| Natalia Landsberg | Collaborator | Universitat de València - Estudi General | UVEG PhD student |
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- dolor; opioides; sistema mesocorticolimbico; ansiedad; anhedonia; adicción
- alcoholismo; adicción; recaída; motivación; estrés; vulnerabilidad
- neuroinflamación; microglia; neurona; sistema opioide
- liposomas; hidrogel in-situ; nose-to-brain; drug delivery
