Scientists at the Department of Cell Biology of the University of Malaga have taken a step forward in the search for more effective treatments for pain with a new study that continues advancing in mitigating the addictive effects of morphine –one of the main drugs used for this purpose– as well as the development of analgesic tolerance to this drug.

Specifically, they have identified that the activation of a dopamine receptor, the D₄, enhances its analgesic effect, and prevents the development of tolerance to morphine. The results of this study have been published in ‘The Journal of Pain’, one of the leading international journals in the field of Pain Science and Medicine.

“Our research group have been addressing the addictive aspects of morphine for more than 15 years, while its role in analgesic tolerance is a more recent line of research,” says Alicia Rivera, professor at the Faculty of Sciences of the UMA, one of the authors of this study.

The expert also points out that reducing its impact at an intestinal level, especially in relation to the problems of severe constipation that it causes, is another line of future research.

Drug target
Rivera explains that morphine remains one of the best analgesics available today for treating pain in modern medical practice. “However, a prolonged administration can lead to problems of risk of dependence and loss of efficacy, as well as the aforementioned issues of constipation and, also, decreased cardiorespiratory function.

This is precisely why it is necessary to find an effective therapy with the least possible side effects, clarifies the UMA researcher, who emphasizes that one possible strategy could be the use of a drug that, when combined with morphine, prevents these unwanted effects.

The scientific team of the UMA, also belonging to IBIMA Plataforma Bionand, proposes using the dopaminergic system, in particular, the D₄R –an understudied cerebral and medullary receptor– as a potential drug target to complement morphine, “thus achieving a safer pain therapy”.

The research is still in its early stages and, so far, it has been carried out in experimental models, so its translation to successful treatments in humans still requires further progress.

Neuronal ‘brake’
“What we have achieved is a potential way to prolong the efficacy of morphine, without having to progressively increase the dose and without increasing the risk of tolerance or pain hypersensitivity,” says the professor of the UMA, confirming that these effects, apart from being dependent on the opioid drug itself, are also conditioned by adaptive changes in the neural circuits of the spinal cord.

Thus, according to the expert, the D₄ receptor would reinforce the inhibitory signals in the spinal cord as a sort of ‘brake’ system that would prevent the pain circuits from entering a hyperexcitable state.

Multidisciplinary team
Led by the R+D group of the UMA ‘IREM’, in this study, which arises in the context of Marina Ponce’s doctoral thesis, the study also involved researchers from the Department of Zoology and the Department of Human Physiology of the Faculty of Medicine of the UMA, as well as a professor at the International University of La Rioja (UNIR).

Mª Ángeles Real, Adrián Ruiz, Belén Gago, Iván Fatuarte, Mireya Moreno, Ismael Aranda and Carolina Roza are co-authors of this multidisciplinary research.