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Project 10740: PaINSIGHT



People involved:


Dr.ir. Jan Buitenweg
Project function: Project Leader
Organisation: Universiteit Twente

Robert-Jan Doll
Project function: PhD student
Organisation: Universiteit Twente

Huang Yang
Project function: PhD student
Organisation: Universiteit Twente

Victor Sluiter
Project function: Technician
Organisation: Universiteit Twente

Dr. Hil Meijer
Project function: Co-applicant
Organisation: Universiteit Twente

Dr. O. Wilder-Smith
Project function: Co-applicant
Organisation: Universitair Medisch Centrum St. Radboud

Prof.dr.ir. Peter Veltink
Project function: Co-applicant
Organisation: Universiteit Twente

Prof.dr. Kris Vissers
Project function: Co-applicant
Organisation: Universitair Medisch Centrum St. Radboud

Prof.dr. Stephan van Gils
Project function: Co-applicant
Organisation: Universiteit Twente


Newsletter (2) November 2012

The aim of the PaINSIGHT project is to use a dynamical system perspective for monitoring of pain processing in the central nervous system in patients developing chronic pain. This approach offers the advantage that multiple individual mechanisms contributing to this function can be observed simultaneously. Insight into the concerted action of the mechanisms – e.g., sensitization and endogenous inhibition – will enable improved selection of adequate treatment or prevention of chronic pain. For this purpose, a psychophysical model is developed allowing simultaneously tracking of multiple thresholds before, during and after a painful stimulus. A first human subject study (N=30) was performed to compare different psychophysical methods.

Application of electrical stimuli with an electrode specifically designed for our purposes (see figure below) results in a perception similar to a sharp prick and is related to activation of the nociceptive system. It is known from literature that the perception of these stimuli changes when another, heterotopic, painful stimulus (e.g. immersing an extremity into cold water, see water-bath filled with cold water in the figure below) is applied. Tracking this perception over time before, during and after the painful stimulus might help us identifying the mechanisms contributing to chronic pain development.

A psychophysical model is developed to continuously apply efficiently chosen stimuli and measure responses to those stimuli. With these stimulus-response pairs, we are able to estimate perception thresholds. A first step was to compare the performance of existing and our own psychophysical methods by means of Monte Carlo simulations and a human subject experiment (N=30). In the human subject experiment, we used cold water as a painful stimulus. The figure below shows the perception thresholds over time (N=30, median and .05 and .95% quantiles). After five minutes subjects were instructed to immerse their hand into the cold water and to remove it again after a maximum time of three minutes. We were able to detect habituation effects as well as an effect due to the cold water.



From literature, we know that different stimulus characteristics have different effects on the nociceptive system due to peripheral and/or central mechanisms. Therefore, if not only the stimulus amplitudes are varied, but also other stimulus characteristics (i.e. number of pulses, pulse width and inter pulse interval), we could obtain different perception thresholds. Then, each threshold belonging to a specific set of stimulus characteristics will provide extra information about the nociceptive system dynamics.
At the moment, we are looking into how many different perception thresholds can be tracked without significant loss of information. First, Monte Carlo simulations provided us information about the effect of simultaneously tracking of multiple thresholds on estimation bandwidth (see figure below). A human subject experiment will be performed to validate the simulation results.



We apply a system approach to quantitatively characterize the malfunctioning of the nociceptive system. We have constructed simple computational models to mimic the forward nociceptive pathway. They contain with four parameters, two time constants and two compound gain-threshold of peripheral fibers and dorsal horn neurons, but with unknown values. We have developed a technique to estimate four system parameters in the forward pathway using 4 or 5 tracked perception thresholds. This approach has the potential to indicate malfunction by displaying differences in parameters for subjects.



To improve the accuracy of the estimation, we plan to utilize the measured stimulus-response pairs in a new estimation approach. This approach might avoid the influence of the bias of the regressed perception thresholds on the estimation of the neurophysiological system parameters and might need fewer data.

Newsletter (1) April 2012

The aim of the PaINSIGHT project is to use a dynamical system perspective for monitoring of pain processing in the central nervous system in patients with developing chronic pain. This approach offers the advantage that multiple individual mechanisms contributing to this function can be observed simultaneously. Insight into the concerted action of these mechanisms – e.g., sensitisation and endogeneous inhibition – will enable improved selection of adequate treatment or prevention of chronic pain.

The PaINSIGHT project is focussed on the development of techniques for dynamic tracking of system parameters under controlled perturbation of system states and on the modeling of the underlying neurophysiological mechanisms.

Presently, fast and accurate techniques are being developed for tracking of dynamical changes in the processing properties such as sensitivity to and temporal integration of pain stimuli by the central nervous system. Furhermore, apparatuses for controlled activation of mechanisms in the central nervous system for inhibition of pain processing are designed and realized. Simultaneously, dynamical mathematical models representing the processing of pain are optimized for identification of relevant system parameters using experimental data.

In a later stage of the project, the developed methods and equipment will be clinically tested at the St.Radboud University Medical Centre in Nijmegen and at the Centre for Human Drug Research in Leiden.


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Introduction
 


The PaINSIGHT project focuses on parameter identification of the nociceptive system for improved monitoring of chronic pain development. The function of both ascending and descending parts of this system can be altered by nociceptive or neuropathic mechanisms. From a mathematical systems point of view, this closed loop system can be regarded as a fast forward system regulated by a slow feedback system. This project aims at development of clinically applicable closed loop identification methods to gain insight in the dynamic properties of the nociceptive system.

PhD-student 1 will develop clinically applicable methods for tracking of multiple thresholds for electrocutaneous stimulation and optimize experimental setups for controlled perturbation of the nociceptive system.

PhD-student 2 will optimize experimental and clinical observations towards meaningful characterizations of the ascending and descending nociceptive system, by development of proper models and subsequent parameter identification methods.

For further information you can contact dr. ir. J.R. Buitenweg (phone +31 53 489 2705, email J.R.Buitenweg@ewi.utwente.nl) or dr. H.G.E. Meijer (phone +31 53 4893416, email meijerhge@ewi.utwente.nl).

Partner

CHDR (Centre for Human Drug Research)