Thematic programme Pain/Opiates

Background and relevance

One of the most significant public health problems worldwide is the lack of procedures for diagnosis and unsatisfactory treatment of chronic pain. Chronic pain including neuropathic and inflammatory pain is extremely disabling conditions with the huge cost for affected individuals and society and loss in work productivity. 10% or more people experience severe and recurring pain. Chronic pain including neuropathic pain induced by nerve injury, disease processes or chemotherapeutic treatments is often resistant to treatment with opioids.

Also, pain including low back and neck pain are critical factors determining work absenteeism in the normal working population. Thus, back pain experienced by 75% of all people is the second leading cause of absenteeism from work, after the common cold and accounts for 15% of sick leaves. For instance, back injuries cause $100 million lost days of work annually in the USA, and are the most costly injury for employers. The cost of a back pain injury claim far surpasses others.

The persistent pain is not only a socio-economical burden, but also causes great individual suffering. The treatment of neuropathic pain is one of the ongoing challenges in current medicine. The patients are often sent to specialized pain centres in order to be helped. There are possibilities to treat these patients with methods out of the reach of a general practitioner, for example different nerve blockades, intravenous ketamine or even spinal cord stimulators.

In Sweden, about 25% of all operated patients, regardless of type of operation, suffer from persistent postoperative pain. The development of such a pain is a complex process reaching from the peripheral nerve through the spinal cord and thalamus to the cortex. Current literature suggests that genetic factors may play a role in the individual perception of pain and in the response for pharmacological therapies and that neuropathy associated with nerve damage in the periphery would have its origin, directly or indirectly, in ion channel function as action potential generation. Signaling pain to the central nervous system would not otherwise be possible. According to recent advances in genetics the polymorphisms of e.g. the m-opioid receptor may explain interindividual variability in pain perception and sensitivity to opioids. Thus, typing of genes related to pain perception and sensitivity to opiates has recently become the subject of research in many clinics. Furthermore, progress in molecular biology has disclosed the structure and function of a number of molecular components (peptides and proteins) involved in nociceptive processing and thereby possible biomarkers of various pain disorders. However, these entities have not yet been validated in patients, i.e. the possibility to probe pain-related constituents in human body fluids remains to be explored.

5-year objectives

The aim of the present theme is to identify relevant markers chronic pain and to develop techniques allowing their assessment in body fluids, preferentially in blood samples. For that purpose we plan to use various animal models for studies of pain sensitivity, development of opioid tolerance and sensitivity. These models will be useful for identifying biomarkers of pain and opiate sensitivity, which also may useful to probe in human samples.

Research projects

Opioid sensitivity

Project leader: Mathias Hallberg, Dept of Pharmaceutical Biosciences, Uppsala University

Participants: Fred Nyberg (UU), Qin Zhou (UU), Jonas Bergquist (UU) and Torsten Gordh (AS) Animal models for biomarker screening Project leader: Mathias Hallberg, Dept of Pharmaceutical Biosciences, Uppsala University

Participants: Qin Zhou (UU), Fred Nyberg (UU) and Jonas Bergquist (UU) Analysis of CFS in patients undergoing pain treatment with electric spinal cord stimulation (SCS)

Project leader: Torsten Gordh, Dept of Surgical Sciences, Akademiska Sjukhuset

Participants: Jonas Bergquist (UU), Fred Nyberg (UU) and Anders Larsson (AS) Analysis of polymorphism of the BH4 gene as a predictor for the developement of chronic pain after surgical injury

Project leader: Torsten Gordh, Dept of Surgical Sciences, Akademiska Sjukhuset

Participants: Fred Nyberg (UU) and Jonas Bergquist (UU) How does paracetamol really work Project leader: Torsten Gordh, Dept of Surgical Sciences, Akademiska Sjukhuset Participants: Jonas Bergquist (UU) and Silvia Orha (AS)

PARTNERS
Uppsala Berzelii Technology Centre for Neurodiagnostics | Email info@berzelii.uu.se