WO2012113909A1

WO2012113909A1 - Using measurements of mental capacity in evaluating the risk of non-malignant chronic pain

Info

Publication number: WO2012113909A1
Application number: PCT/EP2012/053168
Authority: WO
Inventors: Søren BALLEGAARD
Original assignee: Ull Meter A/S
Priority date: 2011-02-24
Filing date: 2012-02-24
Publication date: 2012-08-30

Abstract

The invention relates to a method for assessing the risk of development of chronic non-malignant pain in an individual, comprising (a) determining the level of sympathetic tone in said individual under resting conditions (α), (b) determining the level of sympathetic tone (β) in said individual under a defined psychological workload (Wp) or under or after a defined stimulus (Wp), (c) determining the time (∆t) it takes said individual to revert from the sympathetic tone level β under the defined psychological workload Wp or defined stimulus (Wp), to the sympathetic tone level α under resting conditions, and (d) expressing the risk as a function of β, α and ∆t.

Description

USING MEASUREMENTS OF MENTAL CAPACITY IN EVALUATING THE RISK OF NON-MALIGNANT CHRONIC PAIN

FIELD OF THE INVENTION

The present invention relates to the field of assessment of mental performance capacity in humans. In particular, the present invention relates to methods which enable an accurate determination of an individual's present capacity to manage complex mental challenges, cognitive as well as emotional . The present intervention also relates to the field of predicting/screening future non-malignant chronic pain conditions, which are initiated through a minor stimulus, such as minor surgery, a minor physical accident (car crash as one such example) or a minor psychological or emotional incident.

The invention also relates to the field of chronic pain prophylaxis. BACKGROUND OF THE INVENTION

Whereas it is relatively easy to gauge the physical fitness, there has hitherto not been any effective and simple means of determining the "psychological fitness" of a person. However, the present applicant's international patent application WO 2010/020691 discloses a method for determination of mental capacity, where the behaviour of the measured "psychological fitness" has been shown to resemble that of traditional physical fitness. Is has previously been documented that non malignant chronic pain condition occurs after most kinds of surgical procedures and often at a frequency of > 10 - 15 % - with a subsequent high impact of quality of life, work ability and health care expenses (Perkins F & Kehlet H . Chronic pain as an outcome of surgery: A review of predictive factors. Anestiology 2000; 93(4) : 1123-1133). Until now pre-operative or on-time-of-the-incident identification of individuals susceptible of developing such chronic pain conditions has not been possible. It is also known that persons suffering from chronic non-malignant pain exhibit an impaired Diffuse Noxious Inhibitory Control (DNIC) system, which can be determined by Quantitative sensory testing (Arendt-Nielsen L & Yarnitsky D. Experimental and clinical application of Quantitative Sensory Testing applied to Skin, Muscles and Viscera. J of Pain; 1-17 : 2009). This impairment relates to the polynodal sensor cells, which when located on the chest bone have been found to be a reliable indicator for physiological stress as shown in the present applicant's international patent application publication nos. WO 2005/084529, WO 2006/092146, WO 2006/092146, WO 2009/112570, as well as in WO 2010/020691.

The prevalence for chronic non-malignant pain (defined as pain for more than 6 months) is often higher than 15% in the general population (Eriksen J, Jensen MK, Sjogren P, Ekholm O, Rasmussen N K. Epidemiology of chronic non- malignant pain in Denmark. Pain. 2003; 106(3) : 221-8). Experimental studies have shown increased pressure pain sensitivity of the muscles in these patients (Andersen JH, Kasrgaard A, Frost P, Thomsen JF, Bonde JP, Fallentin N, Borg V, Mikkelsen S. Physical, psychosocial, and individual risk factors for neck/shoulder pain with pressure tenderness in the muscles among workers performing monotonous, repetitive work. Spine. 2002; 27(6) : 660-7.) A common gastrointestinal disorder, like irritable bowel syndrome, has a prevalence of > 10% in many countries. In patients having this disorder, the polymodal sensor of the intestinal wall shows visceral hypersensitivity. These cells are similar to the one used for stress measurement on the chest bone.

In addition, no efficient intervention has been developed with the aim to heal this kind of non-malignant chronic pain .

In conclusion, the field of the intervention is to help screening individuals with respect to development of non malignant chronic main conditions in general and after elective surgery in particular. Furthermore, to link the screening with interventions which have the potential to re-establish normal DNIC. OBJECT OF THE INVENTION

One object of embodiments of the present invention is to provide means for screening individuals with respect to their risk of development of non malignant chronic main conditions in general and after elective surgery in particular.

Furthermore, it is an object of embodiments of the invention to link the screening with interventions which have the potential to re-establish normal DNIC. Also, it is an object of embodiments of the invention to provide methods to assist the professional (as well as the individual) in estimated the risk for developing a non malignant chronic pain condition when/if exposed to a minor stimulation of physical, mechanical, mental, psychological, or emotional character.

DISCLOSURE OF THE INVENTION

Whereas it is relatively easy to gauge the physical fitness, there has hitherto not been any effective and simple means of determining the "psychological fitness" of a person. However, the present applicant's international patent application WO 2010/020691 discloses a method for determination of mental capacity, where the behaviour of the measured "psychological fitness" has been shown to resemble that of traditional physical fitness.

The present inventor has discovered a link between the measurement results obtained from the method in WO 2010/020691 and the incidence of non- malignant pain in surgical patients. In brief, it appears that subjecs exhibiting a high psychological fitness as measured in WO 2010/020691 also exhibits a markedly low incidence of post-surgical non-malignant pain.

The psychological performance capacity (also termed the "psychological fitness" herein) in humans behaves in a manner similar to the physical performance capacity. Instead of using the oxygen consumption or a surrogate thereof as measured variable as is done when determining physical fitness, the level of sympathetic tone or a surrogate thereof can be used as the measured variable. In WO 2010/020691 is disclosed that a series of pilot experiments revealed that there is a tight correlation between a person's psychological work capacity and a "psychological fitness index", PFI, where persons having a high PFI are

characterised by a low resting sympathetic tone, the ability to withstand increasing psychological workload without reaching a maximum sympathetic tone at an early stage during the increase, and, importantly, the ability to revert to the low resting sympathetic tone within a short while after termination of the psychological workload.

Further, as is the case with the physical fitness index, which may be improved by physical training, it has proven possible to increase the psychological working capacity in individuals by using appropriate training. In this context it is noteworthy that one factor which has been found to be decisive for the

"psychological" fitness is an individual's level of mental stress - previous work by the present inventors has shown that psychological stress i.a. has the

consequence that the resting level of sympathetic tone is increased, meaning that the difference between the maximum sympathetic tone and the resting level is decreased - put in simple words, this seems to mirror the fact that the brain's capacity is "occupied" (as evidenced by the high resting level), and the further consequence is that the capacity for increases in psychological workload is decreased to lesser or higher degree in the psychologically stressed individual.

Hence, in one general aspect, the present invention relates to a method for assessing the risk of development of chronic non-malignant pain in an individual, comprising

(a) determining the level of sympathetic tone in said individual under resting conditions (a),

(b) determining the level of sympathetic tone (β) in said individual under a defined psychological workload (W_p) or under or after a defined stimulus (also term W_p),

(c) determining the time (At) it takes said individual to revert from the

sympathetic tone level β under the defined psychological workload or stimulus W_p, to the sympathetic tone level a under resting conditions, and

(d) expressing the risk as a function of β, a and At. In one embodiment, the present invention relates to a method for assessing the risk of development of chronic non-malignant pain by determining the capacity for psychological workload (C_pw) in an individual, comprising

(b) determining the level of sympathetic tone (β) in said individual under a defined psychological workload (W_p) or defined stimulus (W_p),

(c) determining the time (At) it takes said individual to revert from the sympathetic tone level β under the defined psychological workload W_p or under the defined stimulus (W_p), to the sympathetic tone level a under resting conditions,

(d) calculating the psychological workload capacity according to the formula I : C_Pw = (β-α) / (W_p x At) or any monotone function thereof, and

(e) using the psychological workload capacity's value as an indicator of the risk of developing chronic non-malignant pain.

It will hence be understood, that the individual's capacity for psychological work load is determined according to the methods in WO 2010/020691, and that the risk for developing chronic non-malignant pain is expressed based on this capacity. In practical terms, a low capacity provides for an increased risk, whereas a high capacity provides for a lowered risk.

The "capacity for psychological workload" (used interchangeably with the expression "psychological fitness" and "PFI") denotes the ability of a person to manage demanding and complex psychological challenges. The psychological fitness may be measured "internally", i.e. for one person relative to an arbitrary index value (cf. below) measured initially according to the present invention, or comparatively, where the psychological fitness is determined against at least one known psychological challenge which has a standardized assigned value for W_p (cf. below).

Convenient methods for determining the sympathetic tone in an individual are disclosed in WO 2005/084529, WO 2006/092146, WO 2006/092146, WO

2009/112570, as well as in WO 2010/020691, which are hereby all incorporated by reference herein. These patent applications generally deal with methods for determination of the level of psychological stress in humans and animals. The determinations have been obtained by using measurements of the absolute or relative pain threshold in locations in or on the body where the pain perception is dependent on the sympathetic tone. The methods for sympathetic tone determination (and, under some circumstances, the stress level, warning systems sensitivity or other surrogates) which are disclosed in these patent applications are all applicable and preferred for the purposes of the present invention. The values of β and a can accordingly be expressed as functions of the force used to exert a stimulus in a sympathetic tone dependent location so as to reach the threshold of pain. Conveniently, β and a are mathematically derived from the pressure force necessary to elicit pain in sympathetic tone dependent location on the body. The mathematic derivation may be a

logarithmic scale expressing an inverse correlation between the sympathetic tone and the nociception threshold value in such a sympathetic tone dependent location.

In particular, β and a can be measured with an algometer (Nussbaum, E. L, Downes, L. "Reliability of clinical pressure-pain algometric measurements obtained on consecutive days", Phys Therapy 78, 160-169 (1998)). According to the present invention an algometer was used as follows:

In the example, algometer readings were hidden until the measurement was completed in order to blind the subject and researcher. For analysis, the mean of two consecutive measurements was used.

The applied algometer pressure is mathematically transformed into a logarithmic scale of sensitivity levels similar to the Decibel scale, which uses air pressure threshold for the determination of hearing thresholds. Algometric Measure (PT) = Log 200 - Log 100 (100 ^■ threshold in kilogram/14 kilos) (PT unit) (unit = ballegard (bal)). An increase in 30 PT units corresponds to a 100% increase in sensitivity (i.e. lower pain threshold). The scale ranges from 0 to 99, with 0 indicating the highest measurable threshold (i.e. 14 kilograms) and 99 indicating the lowest measurable threshold (i.e. 0.5 kilograms) allowing the instrument to measure a 800% increase in pressure pain threshold.

In order to prevent damage to the skin, an alarm sound was activated when pressure reached a level of 14 kilograms. A special rubber measurement foot plate was developed with the aim of allowing the determination of pressure pain threshold on the bone without applying noxious stimulation to the skin - as such stimulation might lead to determination of skin pressure pain threshold instead.

For clinical use, PT measurement values < 15 were considered normal for men and values < 30 for women.

The phrase "sympathetic tone-neutral point" denotes a point on or in the body in which the sensitivity to an applied stimulation, such as pressure, is independent of the activity level of the sympathetic nervous system. Also covered by the expression is a point on or in the body where increased sympathetic tone causes a higher threshold for sensitivity or nociception in said point or a point, which may show increase in sensitivity, but below the threshold, which is ethically applicable (i .e. 14 kilogram - see above)

The phrase "sympathetic tone-dependent point" denotes a point on or in the body in which the sensitivity to an applied stimulation, such as pressure, is dependent on the activity level of the sympathetic nervous system, in the sense that increased sympathetic tone causes the point to exhibit a lowered threshold for sensitivity and/or nociception.

"Resting conditions" are defined as conditions, at which the individual is at physical and psychological rest, i.e. very much the same conditions that should be applied when determining the resting pulse of an individual - i.e. conditions where the body is at rest and where the environment is quiet and calm and therefore non-stressing for the individual. One such example for standardized use is the sleep during one night or similar. A "defined psychological workload" is in the present context a predefined and reproducible set of psychological challenges designed to mirror a psychological workload (mental, cognitive or emotional), which the individual could face in real life. For instance, the defined psychological workload can be in the form of psychological tasks having an increased complexity over time optionally combined with an increasing environmental challenge in the form of e.g.

increasing noise, frequent interruptions, increasing time pressure etc. The person of skill in psychology will be able to design tests which gauge any one of the types of workload (mental, cognitive or emotional) which are relevant for the subject being tested. In military training, e.g. it is not uncommon to test the soldiers' ability to withstand increasingly complex and demanding situations, in civil life the use of e.g. airplane simulators and other tests of mental

coordination have been in use for decades, and also many computer games involve increasing challenges for the players - these types of challenges are all well suited to gauge the tested subject to "the limits".

A "defined stimulus" is a standardized dose of sensory stimulation of the nervous system e.g. via acupressure or acupuncture. Such a stimulus has the the typical effect that the sympathetic tone is lowered, so in contrast to use of a

psychological challenge, the time measured in the method of the invention is the time it takes before the sympathetic tone is back at its previous higher level. Alternatively, the measurement of the time related to the defined stimulus can be a standardized time interval, where the difference is instead expressed as the relative reversion vis-a-vis the resting level .

The time At depends on several parameters, but under standardized conditions and if the individual has been subjected to a standardized "hard" psychological challenge or defined stimulus, At will be of a higher value than if the same individual has been subjected to a less hard challenge. Formula I compensates for this by dividing W_p with At.

As an alternative to use At, it is possible to devise different or supplementary embodiments, where At_inv, i.e. the time it takes from a resting PFI measurement to reach a defined level under a given psychological workload, replaces At in the methods of the invention detailed above. In these embodiments formula I provides a measurement of the "alertness" of the brain, and can be used to supplement the measurement for capacity.

The value W_p, which is a characteristic of a given psychological challenge, is arbitrary, but should be calibrated and standardized in order to allow

reproducibility, especially in cases where several challenges, such as challenges requiring increasing psychological workload, are used. One simple way to determine the value of W_p for a standardized challenge is to correlate it with a known indicator of stress or sympathetic tone in a number of individuals and then assign a given psychological workload a value relative to other

psychological workloads tested in the same persons. This allows for tailoring of challenges with verified and quantified differences in complexity. For the purposes of the present invention it is preferred to define W_p for a number of different psychological challenges, using formula I as the means for assigning values to W_p: Since a person does not change his or her C_pw within a very short period of time, formula I should ideally provide for the same values of C_pw, irrespective of the challenge W_p, when a person is tested. This means that if the same group of persons within a short while is subjected to a number of different challenges assumed to have different W_p, the result of formula I should be constant for each person. So, accordingly, it is possible to simply assign arbitrary values to a number of predefined psychological challenges for each person and also to use the results from all tested persons to arrive at a standardized W_p value for each psychological challenge (convenient when comparing the psychological fitness with other persons). As a preferred alternative or supplementary test, the response to a standardized dose of sensory stimulation may be employed, in which case the increase in pain threshold during a predetermined time period (i.e. minutes) is measured. This may be supplemented by a recording of the ability to sustain the obtained increase in pain threshold during a subsequent restitutional period (i.e.

minutes). If the objective of the present invention is to only follow the psychological fitness development and thereby development in risk of developing chronic pain of one single person, the person's C_pw can initially be set to any arbitrary number (e.g. 100) and similarly, the initial challenges used may be attributed W_p values accordingly so that formula I provides W_p = 100 in the initial tests with each challenge. After this initial step, the person's development is then followed using the values obtained for the different challenges.

The monotone function may include multiplication of formula I with a gender adjustment factor and/or the monotone function may include multiplication of formula I with an age adjustment factor. Both these options take into

consideration that the capacity for different types of psychological challenges may vary according to age and according to sex. Typically, the value 1 of both these adjustment factors is set relative to the best performing sex or age group based on statistical data in order to compensate for natural variations - if, for instance, elderly normal persons on average exhibit a lower psychological fitness, this may be adjusted by multiplying with a factor which ensures the average performance of each age group is the same. The result is that it becomes possible to compare the psychological fitness directly between different age groups or sexes - in this embodiment of the invention, the PFI is thus used in a manner similar to the IQ, which is, at least for children, age adjusted.

Alternatively, the factors may be omitted in Formula I and in that case it may be convenient to establish the values of at least "average", "below average" and "beyond average" psychological fitness for different age groups and the two sexes. As mentioned above, the sympathetic tone levels are conveniently determined by a method comprising determining the pain threshold in at least one

sympathetic tone dependent location on or in the body. The various means and methods for performing such determinations are provided in the patent applications referenced above. Another aspect of the invention relates to a method for monitoring the development of capacity for psychological workloads in an individual (and thereby the development in the risk of developing chronic pain), said method comprising repeatedly determining the capacity for psychological workload described herein. Such repeated determinations may be made at any interval, but typically repeated determinations are performed at intervals of at least one day, such as at least 2, at least 3, at least 4, at least 5 and at least 6 days. The intervals may be longer, i.e. intervals counted in weeks or in months. It is to be noted that the intervals need not be regular. When over time monitoring a person's capacity for psychological workload, it also becomes possible to incorporate knowledge about the person's

psychological and physical state in order to determine if there are specific situations or circumstances which have a negative impact on the psychological fitness and thereby the risk of developing chronic pain - in turn this allows the person to actively avoid such situations or circumstances or, alternatively, learn to manage such situations or circumstances productively. Hence, in order for this to be effective, a practical approach is to maintain a diary or other record of the daily life of the monitored person.

A third aspect of the present invention is related to the above and concerns a method for increasing the capacity for psychological workload in an individual and thereby decreasing the risk of developing chronic non-malignant pain, the method comprising determining an initial value for the capacity according to the method of the first aspect of the invention, subsequently subjecting the individual to measures which reduce the individual's sensitivity to factors which induce psychological stress and monitoring the development in the individual's capacity for psychological workload according to the methods described herein and in WO 2010/020691 at least until a significant decrease in the value of a and/or a significant increase in the value of At has been observed.

Measures, which may be used to increase the capacity and thereby reduce the risk of developing chronic pain can be selected from a variety of known psychological methods, cognitive methods, meditation techniques, physical exercises, sensory stimulation techniques and simple planning of daily life.

Further, the intervention methods reported in WO 2005/084529, WO

2006/092146, and WO 2008/028976 which aim at reducing stress are all applicable in this third aspect of the invention. The present inventors have discovered that it is possible to quantify the the risk of developing chronic pain when exposed to a minor stimulus of physical , mechanical, mental, psychological, or emotional character in the same way as it is possible to quantify the working capacity of the brain according to WO

2010/020691. Put otherwise, the mental capacity measurements of WO

2010/020691 provide a tool for predicting the risk of a patient or person developing chronic non-malignant pain.

According to the invention, testing and measurements of the capacity for psychological workload may conduced fully through the use of an Internet- guided test program - and while the individual subject or a practitioner may conduct all practical measurements on location during the conduction of the test procedure, all measured values are inputted into a data file on the patient on the web based platform in order to calculate and output the measurement results expressed as a capacity for psychological workload or, in relevant cases, as the risk of developing chronic pain. These findings also enable a computer system for determining the risk of developing chronic-non-malignant pain in a subject or a group of subjects, said system comprising

- a computer readable memory loaded with physiological data for at least one individual, - an input device for entering values α, β, At as defined above and also for entering value W_p as defined above in the event the system accepts more than one value of W_p - in some embodiments, the system is simple and operates with only one value for W_p, whereby it is unnecessary to input it, - a processor programmed to calculate said risk based on α, β and At, and

- an output device for outputting a representation of said risk calculated on the basis of α, β and At.

Such a system is also part of the present invention. The physiological data are typically values/characteristics selected from age, gender, body height and weight, various health status parameters, IQ, and other values which are useful for determining the theoretical maximum performance of a given individual. Thus the physiological data provide an indication, which allow the calculation to be correlated to an individual's overall wellbeing. It is convenient if the computer system according further includes a computer readable memory configured to store previous and future values calculated by said processor. This allows the user to not only get a here-and-now picture of the risk but also to study whether training and intervention has any effect. In any event, if the user's data provides for calculations that indicate deterioration, the system may further include an output device for outputting instructions for intervention in the event a calculated capacity for the risk exceeds a threshold value. Such intervention may be any type of intervention used to reduce the level of stress, cf. above.

In certain embodiments, the computer system outputs the risk based on formula I : (β-α) / (Wp x At) or as any monotone function thereof, wherein the value of W_p is either derived from the input or is a constant stored in said computer system (cf. the above considerations with respect to one or multi-value W_p systems). The monotone function will in certain embodiments be adjusted as discussed above by multiplying with an age and/or gender adjustment factor. The computer system may be implemented on a single computer, i.e. by implementing a software product on a computer, but in a preferred embodiment the input device and said processor are located on separate computers. This enables a client-server solution or most preferred a solution where the separate computers are connected via the internet and where a user can log on to the system and input data from a distant location, while storage and processing of data are performed on an internet server.

Also contemplated are computer program products which, when read into a computer memory can adapt a computer or a network of computers to function as the above described computer system .

EXAMPLES

Heart pain : In a prospective study of 161 patients with non malignant chronic heart pain due to atherosclerosis of the coronary artery vessel (i.e. angina pectoris), the present invention has been used in a real life clinical setting, using the "effect of one nights sleep" as the stimulus, and the change in

measurements as described herein before and after sleep as the indicator for the capacity for psychological workload. The patients were told to use the combined morning findings for a) a high resting mental capacity measurement and b) little or no effect on the measurement from sleep as an indicator for "low capacity for psychological workload" - and as a consequence hereof - advised to be consciously aware of their increased likelihood of developing heart pain if exposed to a mental, psychological and/or physical stimulus of even a minor intensity. With that knowledge the person had the option to avoid such stimuli and thereby to prevent the emergence of heart pain . The results showed that the psychological workload capacity measurements worked in real life.

In this study, the measurements were performed by finger palpation and no quantification as such of the measurements was included. (Ballegaard S, Borg E, Karpatschof B, Nyboe J, Johannessen A. Addition of acupuncture and self-care education in the treatment of patients with severe angina pectoris may be cost beneficial : an open, prospective study. J Altern Complement Med. 2004

Oct; 10(5) : 777-83. )

The present invention uses the same knowledge as in the study of heart patient. However, by conducting objective measurements of the capacity for psychological workload and conduct experimental tests under which conditions the measurements are recorded, it becomes possible to quantify the capacity to withstand stimuli of physical, mechanical, mental, emotional and psychological nature with the later development of non malignant chronic pain Surgical pain : In more than 100 consecutive post-surgery patients (surgery in the chest, abdomen, prostate, cranium and lumbar back), we have conducted measurements of resting values and psychological fitness tests as essentially set forth in PCT/EP2009/06083. In all patients who had elevated resting values of sympathetic tone and who exhibited low low capacity for mental workload, a comprehensive self care educational program - which included sensory nerve stimulation with the aim to restore the impaired function of the Diffuse Noxious Inhibitory Control (DNIC) system - was initiated. When subsequent

measurements according to PCT/EP2009/06083 revealed that the DNIC system was fully functioning again, the patients were instructed to measure the their sympathetic tone/stress level twice daily, observe the resting values as well as the effect of sleep to ensure maintenance of a high capacity for psychological workload. In conclusion with more than 2 years of average observation period, none of these 100 patients developed non-malignant post operative chronic pain (p < 0.001) when compared to data from the scientific literature with respect to the development of post-operative chronic pain .

Whiplash development: We have one example in a 53 year old woman with whiplash syndrome, a high resting sympathetic tone and a low capacity for psychological workload as determined according to PCT/EP2009/06083. In this patient, we could development of chronic pain was not prevented and

subsequently we could bring her resting sympathetic tone measurements down to normal values (< 30) compared to high values (> 60) and her capacity for psychological workload remained low

Claims

1. A method for assessing the risk of development of chronic non-malignant pain in an individual, comprising

(b) determining the level of sympathetic tone (β) in said individual under a defined psychological workload (W_p) or under or after a defined stimulus (W_p),

(c) determining the time (At) it takes said individual to revert from the sympathetic tone level β under the defined psychological workload W_p or defined stimulus (W_p), to the sympathetic tone level a under resting conditions, and

(d) expressing the risk as a function of β, a and At.

2. The method of claim 1, wherein step (d) entails calculating a psychological workload capacity according to the formula I :

(β-α) / (W_p x At) or any monotone function thereof.

3. The method according to claim 1 or 2, wherein the monotone function includes multiplication of formula I with an age adjustment factor.

4. The method according to any one of claims 1-3, wherein the monotone function includes multiplication of formula I with a gender adjustment factor.

5. The method according to claim 3 or 4, wherein the age and/or gender adjustment factor is a positive number, which based on statistical data allows direct comparison of values for psychological workload capacity between different age groups and/or the two sexes.

6. The method according to any one of the preceding claims, wherein

sympathetic tone levels are determined by a method comprising determining the pain threshold in at least one sympathetic tone dependent location on or in the body.

7. The method according to any one of the preceding claims, wherein β is determined after a stress-inducing intervention.

8. The method according to any one of claims 1-7, wherein β is determined after a stress-reducing intervention, such as a standard dose sensory

stimulation.

9. The method according to any one of the preceding claims wherein the psychological workload is selected from the group consisting of mental workload, emotional workload and cognitive workload.

10. A method for monitoring the development of risk of developing chronic non- malignant pain in an individual, said method comprising repeatedly determining the risk according to the method of any one of the preceding claims.

11. The method according to claim 8, wherein repeated determinations are performed at intervals of at least one day, such as at least 2, at least 3, at least 4, at least 5 and at least 6 days.

12. A method for reducing the risk of development of chronic pain in an individual, the method comprising determining an initial value for the risk according to the method according to any one of claims 1-7, subsequently subjecting the individual to measures which reduce the individual's sensitivity to factors which induce psychological stress and monitoring the development in the individual's risk of developing chronic pain according to the method according to any one of claims 8-9 at least until a significant decrease in the value of a and/or a significant decrease in the value of At has been observed.

13. The method according to claim any one of the preceding claims, wherein at least one previous assessment is used as a standard.

14. A computer system for assessing the risk of developing chronic non- malignant pain in a subject or a group of subjects, said system comprising - a computer readable memory loaded with physiological data for at least one individual,

- an input device for entering values α, β, At as defined in claim 1 and also for entering value W_p as defined in claim 1 or a value representing a defined stimulus in the event the system accepts more than one value of W_p or more than one value for the defined stimulus,

- a processor programmed to calculate the capacity for said risk based on α, β and At, and

15. The computer system according to claim 14, further including a computer readable memory configured to store previous and future values calculated by said processor.

16. The computer system according to claim 14 or 15 further including an output device for outputting instructions for intervention in the event a calculated risk exceeds a threshold value.

17. The computer system according to any one of claims 14-16, wherein said computer system outputs said risk based on formula I : (β-α) / (W_p x At) or as any monotone function thereof, wherein the value of W_p is either derived from the input or is a constant stored in said computer system.

18. The computer system according to claim 17, wherein the monotone function is as defined in any one of claims 3-5.

19. The computer system according to any one of claims 14-18, wherein the values of β and a are as defined in any one of claims 6-8.

20. The computer system according to any one of claims 14-19, wherein said input device and said processor are located on separate computers.

21. The computer system according to claim 20, wherein said separate

computers are connected via the internet.