05:47pm Saturday 18 January 2020

More specific targets detected for pharmaceutical drugs to combat pain

However, over the past decades, it has become known that the sensorial apparatus of pain can give rise to disorders which cause the pain to be chronic or disproportionate. The UPV/EHU Pain Mechanisms research team, based at the Department of Neurosciences, has discovered a new molecular mechanism that is responsible for pain chronification. The article describing this finding, entitled, Time-Dependent Cross Talk between Spinal Serotonin 5-HT2A Receptor and mGluR1 Subserves Spinal Hyperexcitability and Neuropathic Pain after Nerve Injury, was published in the Journal of Neuroscience. The research provides a basis for the development of new, more efficacious analgesic pharmaceutical drugs.

The neurotransmitter serotonin fulfils the function, amongst others, of modulating pain. Nevertheless, this research has shown that serotonin also participates in the mechanisms making pain become chronic and disproportionate, and has identified its receptor 5-HT2A as the principal mediator.

According to what the research team has been able to show in an animal model affected by a nerve injury, the activation of the 5-HT2A receptor has direct effects on the receptor of another neurotransmitter – in concrete on the glutamate receptor (mGluR1). Thus, the activation of 5-HT2A causes an over-expression of mGluR1 which, in turn, triggers the activity of 5-HT2A in such a way that this mutual activation increases the pain and tends to prolong it over time. “The work shows that this molecular mechanism is involved from the start of the causal injury, and that it is responsible for the propagation of the pain to anomalous locations without apparent anatomical relation such as, for example, the side of the body opposite the injury”, explained Doctor Jatsu Azkue, Director of the Pain Mechanisms research team.

The results of the research have consequences for the current strategy of increasing the quantity of serotonin neurotransmitter in the nervous system to act against pain. “We have seen that serotonin does not always reduce pain, and can even contribute to worsen the situation”, explained Professor Azkue. “A better strategy for increasing the quantity of serotonin could be to control its less desirable effects through using pharmaceutical drugs which block the activation of its 5-HT2A receptor or which act simultaneously on this and on the glutamate receptor mGluR1”, he added.

The team that has taken part in this research is made up of researchers from the Faculty of Medicine and Odontology of the Faculty of Pharmacy. The research forms part of the PhD thesis of the lead author of the work, Mr Zigor Aira.

Farmakologia, Medikuntza, Osasuna  

Internet reference
Time-Dependent Cross Talk between Spinal Serotonin 5-HT2A Receptor and mGluR1 Subserves Spinal Hyperexcitability and Neuropathic Pain after Nerve Injury Zigor Aira, Itsaso Buesa, Mónica Gallego, Gontzal García del Caño, Nahia Mendiable, Janire Mingo, Diego Rada, Juan Bilbao, Manfred Zimmermann and Jon Jatsu Azkue The Journal of Neuroscience, 26 September 2012, 32(39): 13568-13581; doi: 10.1523/JNEUROSCI.1364-12.2012
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