Noci-Plas

Chronic pain has a high prevalence in the population, significantly affecting the lives of patients. The development of effective and safe therapies to improve pain treatment is a social and economic priority. Following injury, the function of nociceptive pathways is altered, leading to sensitisation processes that can trigger abnormal and long-lasting forms of pain. Changes occurring at the level of the spinal cord contribute to the increase in excitability in these circuits, thereby facilitating the development of chronic pain.
The present project will contribute to the understanding of the mechanisms involved in the development of chronic pain by studying different forms of induction of spinal cord sensitisation as well as the underlying cellular mechanisms. To this end, novel ex vivo sensitisation models will be developed and used. Our initial hypothesis is that specific sensitisation processes occur depending on the type of nociceptive afferents involved in their initiation.
The studies will involve the use of electrophysiological recordings from spinal cord neurons using ex vivo spinal cord preparations. The responses of these neurons to optogenetic stimulation of specific nociceptor populations will be studied using stimulation protocols designed to induce plasticity in nociceptive circuits. The neurobiological mechanisms triggered by these sensitisation processes will be analysed, including changes in the excitability of dorsal horn neurons and in the synaptic transmission that may be responsible for generating a state of hyperexcitability.
The proposed studies will represent a significant advance in the knowledge of the mechanisms of chronic pain generation. The characterisation of specific mechanisms will allow the identification of potential strategies for the treatment of pain, thereby improving the quality of life of patients suffering from chronic pain. The impact of our work will be enhanced by the development of ex vivo sensitisation models for use in preclinical studies to evaluate the antinociceptive potential of new analgesic compounds.