Overview

The pain that we experience when encountering a potentially injurious impact or immediately after a tissue injury, is an important warning signal. It triggers an “escape reaction” and draws our attention to an imminent or actual tissue damage. Similarly, the pain that is associated with the development of diseases is of huge biological benefit, as it again alerts us to potentially life-threatening processes and, by discouraging the use of the affected area, promotes healing. However, persistent pain, which is associated with healing processes, currently incurable diseases or indeed with no apparent disease, does not offer any biological benefit. On the contrary, persistent pain, which is often severe and becomes chronic, is detrimental, results in suffering and poor quality of life. Persistent pain in fact is regarded as a pathological condition, a disease in itself. Importantly, persistent pain is difficult to reduce to a satisfactory level with the currently available approaches. However, the lack of proper control of persistent pain may lead to the development of physical and mental disabilities, which further devastate the patient’s quality of life. The main goal of our research activities, in order to develop new pain killers and improve patient care, is to identify pivotal cellular and molecular mechanisms in neuronal information processing that is induced by various persistent painful conditions and results in the development of persistent pain.  

In order to develop new pain killers and improve patient care, the main goal of our research activities is to identify pivotal cellular and molecular mechanisms in neuronal information processing that is induced by various persistent painful conditions and results in the development of persistent pain.  

Summary of our current research

Our current research activities include three major areas:

Molecular mechanisms of signalling between diseased tissues and the nervous system
The overwhelming majority of persistent pain is associated with diseases, such as tissue injury due to various traumas, rheumatoid- or osteoarthritis or cancer. Diseased tissues initiate signalling that leads to the development of pain by inducing activity in specialised neurons called pain-sensing (nociceptive) primary sensory neurons, by a largely unknown repertoire of agents. Disrupting that signalling is expected to reduce pain. Our aim is to define the chemical fingerprints of diseased tissues and to determine the cellular and molecular effects of key agents in nociceptive primary sensory neurons.    

Epigenetics and pain
The development, and particularly the maintenance of persistent pain depend on changes in the expression of a series of currently largely unknown genes in various neurons. The regulation of gene expression, in turn, largely depends on epigenetic mechanisms that induce changes in gene expression without alterations in the DNA sequence, and include DNA methylation, histone modification and actions by non-coding RNA. Elucidating changes in epigenetic mechanisms in painful conditions could contribute to better pain control because epigenetic mechanisms may be controlled. In addition, studying changes in epigenetic mechanisms will lead to the identification of alterations in networks of genes, which are pivotal in the development and maintenance of persistent pain. Our aim in this area is to identify histone modifications that are induced by various painful diseases, and the effects of those modifications in gene expression, particularly in primary sensory neurons and spinal dorsal horn neurons.

Utilisation of the endocannabinoid system to reduce pain
The endocannabinoid system, which consists of receptors (i.e. CB1 and CB2 receptor), ligands (i.e. anandamide and 2-arachidonoylglycerol), transporters and enzymes that synthesise or degrade the ligands, is involved in various neuronal processes including the development of pain. Therefore, the endocannabinoid system has been identified as a major target for pharmacological intervention to control pain. In this area, our activities focus primarily on the expression and activity of anandamide-synthesising enzymes in pain-sensing primary sensory neurons and in the spinal cord, and on the effect of endogenous anandamide on neuronal information processing induced by painful conditions.