PreSinPain project

Chronic pain is currently an important medical-social problem. Developing more effective treatments requires a deeper knowledge on the processing of nociceptive information. At the level of the spinal cord, primary afferent depolarization (PAD) is a physiological mechanism for the control and selection of afferent sensory information, which may produce a dynamic regulation of incoming signals. In processes of persistent pain, this phenomenon can be altered, reducing its inhibitory capacity or even producing excitatory effects, which contributes to the generation and maintenance of pain.
We think that an increase in firing synchrony in the network of interneurons located in the superficial dorsal horn could generate these changes in PAD. To test this, electrophysiological recordings of primary afferents and dorsal horn neurons will be carried out using in vitro spinal cord preparations obtained from mice, which together with optogenetic procedures, will allow the study of different elements of the network and modify their activity. We will analyze the activity of the network in control animals and in others subjected to peripheral inflammation. Additionally, pharmacological approaches with positive allosteric modulators of GABA-A receptors will be made in order to assess their ability to return the activity of these circuits to normal.
The proposed studies analyze the mechanisms of pain generation and may lead to the identification of therapeutic targets of clinical and industrial interest. The development of new treatment strategies will improve the quality of life of patients with chronic pain.