Abstract:

Essential hypertension is still one of the most common cardiovascular conditions. Although it normally has no clinical symptom many reports have confirmed its link with decreased pain perception (hypoalgesia). Patients with Borderline hypertension (140-159 / 90-99 mmHG) are known to be at great risk of progressing to established hypertension. However, due to the absence of long term prognosis it is still unclear whether to start treating them pharmacologically with blood pressure lowering drugs once they are diagnosed. Few studies have confirmed the presence of hypoalgesia in Borderline hypertensives but none has comprehensively compared their cardiovascular and behavioural responses to pain with normotensives and hypertensives at the same time. We subjected three different blood pressure groups (Normotensive, Borderline and Hypertensive) to two different forms of pain stimuli (Cold Pain and Ischemic Pain) and examined their pain tolerance and rating and their blood pressure reactivity to each stimulus. We also investigated the effect of distraction on those factors. The results showed that Pain tolerance and rating in response to Cold Pain was lowest in normotensives and almost similar in Borderline and Hypertension groups. However, distraction affected Normotensive and Borderline groups only by increasing their pain tolerance. Blood Pressure reactivity to mounting pain was highest in Hypertensive group, lowest in Normotensive group and intermediate in Borderline hypertensive group. The response of the three groups to ischemic pain was less clear. These results suggest that Borderline Hypertensives do not react to Cold Pain in the same way as Normotensive individuals do, but the effect of distraction on their reaction to pain and the corresponding blood pressure responses suggest that they may still respond to non-pharmacological treatment in the effort to prevent their progression to established hypertension.

Introduction

Hypertension (high blood pressure) is one of the most common cardiovascular conditions. In the UK one in every three women and two in every five men over the age of 60 has high blood pressure. Overall, hypertension affects around 16 million people in the UK[1]. According to the British Hypertension guidelines criteria hypertension is defined as sustained systolic blood pressure ≥140 mmHG and diastolic blood pressure ≥ 90 mmHG. Normal blood pressure is defined as systolic blood pressure < 140 mmHG and diastolic blood pressure < 90 mmHG[2]. Individuals whose systolic blood pressure is in the range of 140-159 mmHG and diastolic BP in the range of 90-99 mmHG are also known as �Borderline Hypertensive�.

Hypertension can either have no direct cause (essential or idiopathic hypertension) or it can be the result of a primary disease like kidney and adrenal glands disorders (secondary hypertension). Essential hypertension accounts for 95% of all cases.

Essential hypertension is rarely accompanied by clinical symptoms. Nevertheless, it is a risk factor for many serious and sometimes fatal complications like Atherosclerosis, aortic aneurysm, heart and kidney failure, strokes and myocardial infarction. The absence of symptoms means that hypertension can go undetected and therefore uncontrolled in hypertensive patients who remain unaware of their condition until they develop secondary complications.

Interestingly, in 1979 it was first reported that high blood pressure is associated with decreased pain perception or hypoalgesia in rats. In a study by Zamir and Segal (1997)[3] laboratory rats were made chronically hypertensive by clipping their renal arteries. The rats were subjected to noxious thermal stimulations and they showed behavioural hypoalgesia demonstrated by a relatively delayed escape reaction to the stimulus compared to their response before renal artery clipping. In the same year another study by Drowkin et al.²⁴showed that laboratory rates made hypertensive by phenylephrine injection have decreased response to noxious trigeminal nucleus stimulation compared to their response after saline infusion. Subsequent work on other animals also confirmed the link between high blood pressure and decreased pain perception or hypoalgesia[4].

Hypoalgesia in humans

Hypoalgesia was reported for the first time in humans in 1980 in a study by Zamir and Shuber[5]. Evaluationof subjective pain perception was achieved by subjecting 21 essential hypertensivepatients and 34 normotensive volunteers to a non-invasive, gradedelectrical stimulation of the tooth pulp. The results showed that hypertensives have a higher pain threshold compared to normotensives. Other studies investigated the same principle in borderline hypertensives and also concluded that they have lower pain perception and higher pain thresholds than normotensive controls [6] [7] [8] [9].

The mechanism of Pain

Pain is defined as "an unpleasant sensory and emotional experience associated with actual or potential tissue damage"[10]. It is a subjective experience comprised of three major physiological components: sensory-discriminative, motivational-affective and cognitive-evaluative[11]. Behavioural responses to pain depend on the interaction between those three factors. Following a noxious stimulation the sensory receptors carry the nociceptiveimpulses from the site of stimulation via the A-δ and C fibres towards the dorsalhorn of the spinal cord. At this stage, nociceptive impulses are modulated before they travel to higher brain centres where they undergo further modulation[12]. The gate theory proposed by Melzack and Wall�s suggests that nociceptive transmission across the spinal cord is modulated by ascending and descending supraspinal inhibitory inputs that determine what information about pain can be sent to the higher centres in the brain.

Cause of relationship between hypoalgesia and high blood pressure

The relationship between hypoalgesia and hypertension is not a simple causal relationship. There are three possibilities that can explain it: (i) Hypoalgesia may be a secondary by-product of hypertension, (ii) Hypertension is a result of hypoalgesia or (iii) they are both related to a common pathophysiological mechanism. Many studies attempted to investigate those possibilities. Three independent studies refuted the first possibility after they found that treating hypertensive subjects with blood pressure lowering agent did not decrease pain thresholds compared to pre-treatment[13] [14] [15]. These studies concluded that hypoalgesia and hypertension result from a common underlying physiological disorder that does not simply disappear when blood pressure is pharmacologically lowered. Moreover, increasing blood pressure experimentally in normotensive individuals by using pressor drugs did not change pain perception that would have otherwise increased if hypoalgesia was simply a result of elevated blood pressure[16]. This finding provided further supporting evidence that hypoalgesia is not a result of hypertension. The second possibility that hypoalgesia precedes the onset of hypertension in predisposed individuals was reported in animal[17] [18] [19] and human studies[20] [21]; It was found that individuals with positive family history of hypertension perceive pain less than individuals with a negative family history regardless of their actual blood pressure levels[22] [23] . These findings were refuted by other studies by Ghione et al (1988) 13 and Al-Absi et al[24] who found no correlation between pain perception and family history of hypertension. Taking all these studies together, the general belief supports the idea that hypoalgesia is not a direct result of high blood pressure levels, and despite the numerous studies that have dealt with hypertensive hypoalgesia, the exact underlying relationship is still unclear.

Possible underlying mechanisms

The mechanism underlying the phenomenon of hypertensive hypoalgesia remains to be identified. Many hypotheses have been proposed: (i) The baroreflex system: this model suggests that the baroreceptor reflex system responsible for detecting changes in blood pressure modulates pain transmission at the spinal level resulting in reduced pain perception in hypertensive individuals [25] [26] [27] [28] [29]. (ii) The endogenous opioids hypothesis suggests that those neurotransmitters are responsible for pain modulation in hypertensive mammals. Advocates of this model drew their conclusions after they noticed that opioids levels are high in many areas of the CNS of hypertensive rats and that opioids antagonists like Naloxone did suppress hypertension-associated hypoalgesia in those rats [30] [31] [32] [33] [34]. (iii) The descending supraspinal modulation hypothesis: Studies supporting this model suggest that cardiovascular integration and pain modulation centres in the brainstem are closely related and that hypertensive hypoalgesia is actually a result of a common dysfunction which results in tonic descending supraspinal inhibitions from these centres [35] [36] [37] [38] [39].

The effect of distraction on hypertensive hypoalgesia

It has been reported in many studies that shifting attention from the noxious stimulus results in a significant reduction in pain perception [40] [41] [42] [43] [44] [45] . Results show that pain processing areas in the brain also known as the �pain matrix� are less activated during cognitively demanding tasks. Those areas includethe somatosensory and motor cortices (the parietaland prefrontal cortices), the affective division of the anterior cingulate cortex (ACC), the Insula, thalamus and cerebellum2 [46] [47]. Some of those areas (posterior parietal cortex, the ACC, dorsolateral prefrontalcortex and thalamus) are known to be involved in processes involving attention, anticipation and memory[48]. Subjects always reported less pain when they were distracted.

Clinical relevance

Many reports gave firm evidence on the relevance of hypertensive hypoalgesia in the clinical perspective. Some studies have shown that people with arterial hypertension are almost twice as prone to unrecognized (painless) myocardial infarctions as normotensives[49] [50] [51] (See Fig1). In other studies silent myocardial ischemia -which is characterized by the absence of clinical symptoms- was found to be twice as common among hypertensives as among normotensives[52]. Patients with silent myocardial ischemia have also been reported to have higher pain thresholds[53] and higher resting blood pressure[54] than patients with symptomatic (painful) myocardial ischemia. All these studies confirm the link between essential hypertension and hypoalgesia. In fact, Pain is considered to be a useful symptom for many cardiovascular disorders. The absence of this symptom is a negative prospect. Therefore, in clinical terms, hypertension and hypoalgesia become a harmful combination. Indeed, hypertension-related hypoalgesia explains why angina is often poorly perceived and even unreported by hypertensive patients. Those patients may ultimately experience potentially fatal myocardial infarctions or other serious cardiovascular problems without prior clinical warning. For this reason hypertension is commonly known as the �Silent killer�. On the positive side, if hypoalgesia is confirmed to characterize hypertension risk, it (hypoalgesia) can serve as a valuable behavioural marker that identifies those who are at risk and who can benefit from lifestyle changes or drug therapy.

Fig 1: Framingham Study ⁵¹

Blood Pressure Status and Unrecognized Myocardial Infarction in

In the UK the current guidelines for the management of hypertension[55] recommend immediate antihypertensive drug therapy for patients with BP above 160/100 mmHG, and for patients with BP ≥ 140/90 mmHG if they have Diabetes Mellitus.

For patients with borderline hypertension (BP: 140-159/90-99 mmHG), the current guidelines recommend drug therapy only if: (i) there is evidence of any complications of hypertension or any target organ damage, or diabetes and/or (ii) if the estimated 10-year cardiovascular risk is ≥ 20%. If those factors are not present then vigorous lifestyle changes are advised for patients and monthly BP monitoring is carried on them for a year. Lifestyle changes include: (i) weight reduction (in case patient is overweight), (ii) (DASH diet): reduction of dietary fat intake especially saturated fats and increase fruit and vegetables, (iii) reduction of dietary sodium intake, (iv) engaging in aerobic exercise, and (v) reduction of alcohol intake. Antihypertensive drug therapy is started if the lifestyle approach is not successful in lowering the BP of borderline hypertensives in one year55. In fact, long term prognosis is still unclear in borderline hypertension and it remains clinically difficult to decide whether to start pharmacological antihypertensive therapy with those patients once they are diagnosed in the same way as with established hypertensives. It is also unclear whether all borderline hypertensives progress to become established hypertensives.

More knowledge of borderline hypertension is needed in order to better categorize them and establish a more specific and decisive treatment scheme.

Pain perception in borderline hypertensives was assessed in a handful of studies.

Rosa et al^{7
9}and Schobel et al¹⁶ examined and compared pain tolerance in borderline hypertensive individuals and normotensive controls. Only in one study by Ghione et al¹³was the behaviour of borderline hypertensive subjects in response to pain compared to that of normotensive patients and hypertensive controls. Ghione et al used electrical tooth pulp stimulation to determine and compare sensory and pain thresholds among the three groups. All studies strongly showed that borderline hypertensive subjects exhibit hypoalgesia and that they are more pain tolerant relative to the normotensive subjects. Furthermore, Ghione et al found that borderline subjects had the same pain tolerance as hypertensive subjects. Taken together, all these studies showed that: first, hypoalgesia is a feature of hypertension irrespective of the extent of blood pressure levels, second, that pain perception was associated with sustained blood pressure levels rather than transient or fluctuating resting blood pressure levels, and third that borderline hypertensive subjects react to pain in an intermediate way between normotensive and hypertensive subjects.

The possibility of identifying borderline hypertensives through their reaction to pain seems a promising prospect. In order to understand more about borderline hypertension and get a clearer view on their clinical progression and physiological behavior we decided to take the study by Ghione et al further with the aim of answering the same question: How do borderline hypertensives react to pain compared to normotensive and hypertensive subjects?

Aims

The aims of our study are: (i) to assess the cardiovascular responses and pain perception in borderline hypertensives, normotensives and newly diagnosed hypertensives. (ii) To investigate the effects of distraction on those responses. (iii) To compare the above findings among the three groups and assess the position of borderline hypertensives in relation to the other two groups. To answer this question, we decided to subject the three groups to two forms of pain that are different from the one used in the similar study by Ghione et al. The noxious stimuli we used are Cold pain and Ischemic pain. To induce cold pain we used the Cold Pressor Task (CPT) technique which has been used in many previous studies involving pain, autonomic reactivity, and hormonal stress responses[56] [57] [58] [59] [60] [61] [62] [63]. It involves placing a hand in cold water, which delivers a stimulus that produces a gradual pain of mild to moderate intensity[64] [65] [66] [67]. The CPT is a convenient method for assessing sensitivity to cold pain. It produces natural pain and is non-invasive, safe and easy to administer.

To induce ischemic pain we used the Forearm Muscle Ischemia Task. It involves a period of lower arm exercise followed by the inflation of a pressure cuff on the upper arm of the subject. This results in the occlusion of blood flow to the muscles of the lower arm and results in ischemia. The use of muscle ischemia as a means for inducing pain has been documented in many studies[68] [69] [70] [71]. Like the Cold Pressor Task, this method is both safe and non-invasive and generates gradual pain. Another characteristic of this method is that it generates ischemic pain similar to clinical angina. It is also notable that the Cold Pressor Task and Forearm Muscle Ischemia techniques have not been previously used in the study of pain perception in Borderline hypertensive subjects.

Methods

The study consisted of 44 subjects: 32 hypertensive subjects and 11 normotensive subjects (See Table 1 for age and gender descriptions). They were classed into three groups: H (Hypertensive), B (Borderline) and C (control). Group �H� consists of 22 subjects with established hypertension (BP ≥ 160/100 HG). Group �B� consists of 12 subjects with borderline hypertension (BP = 140-159/90-99 mmHg). Group �N� consists of 11 subjects with normal blood pressure (controls) (BP < 140/90 mmHg) (see table 1 and 3). Classification was confirmed by means of clinic blood pressure measurements and ambulatory blood pressure monitor (ABPM) (Spacelabs Medical Inc. - Model 90207-Washington USA) that fits around the upper arm and records mean blood pressure over a 24hr period.

All subjects except for controls were recruited from Dr Una Martin�s hypertension clinic at the Wellcome Trust Clinical Research Facility-Queen Elizabeth Hospital. Controls were recruited from the general population by advert.

The exclusion criteria for all participants included any physiological disorder that may influence cardiovascular responses and pain perception. This includes any kidney or liver problems, cardiovascular diseases (except primary hypertension), secondary hypertension, any other chronic disease (e.g., Raynaud�s disease, diabetes mellitus, angina, migraine�), and any use of medication that may affect those responses: cardiovascular medications, caffeine and alcohol consumption before the study, usage of opiates, analgesic, narcotics, painkillers or non-steroidal anti-inflammatory drugs within three days prior to testing. Exclusion criteria also included alcohol intake above 21 units for men and 14 units for women (1 UK unit of alcohol equals 284 ml of beer, 125 ml of wine or 25ml of spirits). Testing took place in the patient area at the Wellcome Trust Clinical Research Facility-Queen Elizabeth Hospital. Ethical approval was obtained from the Local Research and Ethical Committee.

Table 1: Descriptive statistics of gender and mean age of participants

Hypertensive: (H) Normotensive/control: (C) Borderline: (B)

Male, Female

Mean Age

Std. Deviation

N

B

F

37.75

6.946

4

M

41.75

4.924

4

Total

39.75

5.970

8

C

F

36.00

10.354

6

M

32.60

11.610

5

Total

34.45

10.520

11

H

F

39.33

9.849

9

M

46.36

12.460

11

Total

43.20

11.638

20

Before the experiments

Participants underwent medical screening and physical examination to assess their eligibility for inclusion in the study. This included information on any possible chronic illness, smoking habits, alcohol consumption and possible family history of hypertension.

Eligible participants were then provided with a comprehensive information sheet that describes the experimental procedure, potential risks and implications of the study. A consent form was then signed by the participant and by the overseeing doctor. Following this, participants were asked to complete four different questionnaires (see questionnaires and pain rating chart).

Height and weight were then measured and the Body Mass Index was determined using the following equation[72] [73]

BMI (Kg/m²) =

(Weight in Kilograms)
(Height in Meters)²

Next, participants were asked to be seated comfortably for 10 minutes during which resting blood pressure and heart rate measurements were taken 3 times. All blood pressure measurements in this study were taken by means of an automated blood pressure monitor (Omron 705 CP, Matsusaka Co. Ltd, Japan) attached to the dominant arm. This was then followed by the first experiment.

Experiment 1 - Cold Pressor Task (CPT)

The first experiment carried out was the Cold Pressor Task (CPT). It involves placing a hand in cold water which delivers a stimulus that produces a gradual pain of mild to moderate intensity[74] [75] (See Fig. 2). In our study, we assessed cold sensitivity during an initial resting baseline, a distraction phase and a final resting baseline. The aim of this experiment was to evaluate: (i) pain perception (pain rating and pain tolerance), (ii) cardiovascular reactions (Systolic and Diastolic Blood Pressure) in response to cold pain and (iii) the effect of distraction on those two factors.

The setting consists of a bucket containing cold water at 4�C prepared by adding a portion of ice into tap water in the bucket. Water temperature was monitored by means of a digital thermometer (Control Company-Taiwan) that has a long extension at the end of which a metal sensor records the temperature of water. The blood pressure monitor was fitted on the dominant arm throughout the experiment. Participants were asked to place their hand in the water up to the wrist for 2 minutes. This was the initial pre-distraction phase and will be referred to as Cold Pressor Task 1 (CPT_1). The same procedure was then repeated again with the introduction of a distractive element consisting of a �number repetition� audiotape. Participants listened to the audiotaped presentation of a series of single-digit integers ranging from1 to 10 delivered at 3-4 seconds intervals. They were asked to privately keep count of the occurrence of the number �9� and say how many times they heard it at the end of the experiment. This was the distraction phase and will be referred to as Cold Pressor Task 2 (CPT_2). The procedure was repeated again for a third time without the distractive element i.e. exactly as Cold Pressor 1, in order to examine any changes in the responses following the distraction phase. This was the post-distraction phase and will be referred to as Cold Pressor Task 3 (CPT_3). During each phase pain rating (see questionnaires section) was taken at 30 seconds intervals and blood pressure and heart rate were taken twice, at 0 sec and 60 sec. If subjects had to stop and take their hand off due to extreme discomfort before the 2 minutes was up the finish time was recorded. Between each phase there was a 5 minute rest period during which participants complete a short form of the McGill questionnaire (SF-MPQ). (See Questionnaires section)

Experiment 2- Forearm Muscle Ischemia Task (FMIT):

The aim of this experiment was to assess sensitivity to ischemic pain in the three groups. The blood pressure monitor was again fitted on the dominant arm throughout the experiment. Another inflatable cuff was fitted around the other upper arm. Participants were asked to perform rhythmic forearm muscle contraction for 120 seconds with the arm that had the fitted inflatable cuff. Contraction was done using a dynamometer device (Lafayette Instrument Company). This device has a maximum load of 50 Kg (110 Lbs.). The contraction load for each subject was set at 50% of his/her best of three maximum voluntary contraction attempts. Contraction and relaxation of the dynamometer was paced at 30 contractions per minute for all subjects by means of an audible beeper (Seiko Digital Metronome, China). Subjects had to follow the beep during contraction. At exactly 105 seconds of contraction the cuff around the exercising arm was inflated to 220 mmHG in order to occlude blood flow to the forearm. When contraction stopped (at 120 sec), subjects were asked to relax their arm and sit quietly for another 5 minutes (See Fig. 3). During this time they provided a pain rating every 30 seconds; the first blood pressure and heart rate readings were taken at 120 sec, and then at 240 sec and 360 sec. If participants terminated the task before 5 minutes was up, the finish time was recorded. At the end of the task subjects completed a short-form McGill Pain Questionnaire.

At the end of testing subjects were asked to remain seated for another 10 minutes where 3 blood pressure and heart rate measures were taken.

Fig. 3: Forearm Muscle Ischemia Task

Pain tolerance Time for a subject in any task was the maximum time the subject voluntarily tolerated in that task. Every Cold Pressor Task involved a 120 seconds hand immersion and the Forearm Muscle Ischemia task ran for 300 seconds. If a task was terminated before the allocated time was up the finish time was recorded as the maximum tolerated time.

Questionnaires

The questionnaires that participants had to complete before the experiments were: State Anxiety Inventory (SAI), Trait Anxiety Inventory (TAI), Pain Catastrophizing Scale (CSQ) and Coping Strategy Questionnaire (PCS). After each set of experiment, all subjects completed a Short Form McGill Questionnaire (SF-MPQ). (See Appendix A)

The Short Form McGill Questionnaire (SF-MPQ)

The original McGill Pain Questionnaire was developed in 1975 by Ronald Melzack as a means for measuring the quality and quantity of clinical pain[76]. Due to its lengthiness for some studies another short form of the questionnaire was developed by Melzack in 1986. The Short Form McGill Pain Questionnaire (SF-MPQ) is the one we used in our study and it takes about 2-3 minutes to administer[77]. It is composed of three subscales which provide information on sensory, affective and overall pain intensity. The sensory aspect of pain is represented by the following 11 descriptions in the Sensory Pain Rating index (SPR) of the questionnaire: Throbbing, Shooting, Stabbing, Sharp, Cramping, Gnawing, Hot-Burning, Aching, Heavy, Tender and Splitting. The affective aspect of pain is represented by the following 3 description in the Affective Pain Rating index (APR): Tiring-Exhausting, Sickening, Fearful and Punishing-Cruel. The Sensory and Affective Pain indexes are all ranked from (0) to (3) in arbitrary units, where (0) represents no pain, (1) represents mild pain, (2) represents moderate pain and (3) represents sever pain. The score range of Sensory Pain index is (0 to 33) and that of Affective Pain index is (0-11) (arbitrary units). The SPR and APR provide feedback on the quality of pain. The Overall Pain Intensity (OPR) provides feedback on the overall intensity (quantity) of pain. It consists of the Present Pain Intensity (PPI) and the Visual Analogue Scale (VAS). The PPI consists of six words of incremental intensity and corresponding numbers (0 to 5) describing the overall pain level: No pain (0), Mild (1), Discomforting (2), Distressing (3), Horrible (4) and Excruciating (5). The VAS section consists of an empty space in the questionnaire sheet where subjects can rate their overall pain experience by writing down a number ranging from 0 (for no Pain) to 100 (worst possible pain).

The pain rating requested from subjects every 30 seconds during our experiments is based on the VAS. Participants were asked to verbally provide a number from 0 to 100 in this which is noted down in the results sheet where all readings and measurements are recorded.

The State Anxiety Inventory (SAI) and Trait Anxiety Inventory

It has been reported that the psychological and mental state affects pain perception. Anxiety is known to amplify pain experience in painful procedures[78] [79] [80] [81] [82] [83] [84] [85]. The State Anxiety Inventory and Trait Anxiety Inventory (SAI) and (TAI) developed by Speilberger C.D. in (1966)[86] are useful tools used to measure the levels of anxiety. They consist of 20 questions each and take 2-3 minutes to complete. The SAI provides information on the temporary condition of "state anxiety" in subjects during the time of completion of the questionnaire. The (TAI) provides information on the more general and long-standing quality of "trait anxiety"[87]. Both questionnaires evaluate feelings of apprehension, tension, nervousness, and worry. The effect of those feelings on pain perception and cardiovascular modules both on the short and long term has been previously studied and confirmed^{81 82 85}_.We wanted to test for any differences in feelings of apprehension, tension and nervousness among our subjects and determine their influence on pain perception and cardiovascular reactions in our study. All questions were ranked in magnitude from (0) to (4) (arb.units). The sum of scores in each questionnaire was used for data analysis. The higher the score the greater is the level of anxiety and vice versa.

The Pain Catastrophizing Scale and Coping Strategy Questionnaires

Different people cope or deal with pain in different ways. Some have strategies to divert the attention from the source of pain whereas others panic or even feel helpless in dealing with pain.

The Pain Catastrophizing Scale

The process of "Catastrophizing" pain is common among some people. �Catastrophizing� is magnifying or exaggerating the threat value or seriousness of the pain sensations during painful procedures[88]. It contributes to more intense pain experience and augmented emotional distress [89] which reflects in higher pain ratings and lower pain tolerance time in people who catastrophize pain. The Pain Catastrophizing Scale (PCS) was initially created to measure the effects of Catastrophizing pain in post surgical patients and pain related experiments[90]. This questionnaire assesses three components of Catastrophizing: rumination (reflection or meditation), magnification, and helplessness. All questions were ranked in magnitude from (0) to (4) (arb.units). The individual scores for all PCS questions (PCS_1 to PCS_13) were added together and the total (PCS Total) was used in data analysis.

Coping Strategy Questionnaire

�Coping generally refers to the strategies that individuals use to minimize the impact of life stressors on their psychological well-being�[91]. Many strategies can be developed by individuals in order to reduce the distress or unpleasantness of pain. The Coping Strategy Questionnaires CSQ was created to assess different coping strategies. It comprises 44 questions grouped in 9 sets each assessing a different strategy: Diverting attention, Coping Self-Statements, Ignoring Pain Sensations, Reinterpreting Pain, Praying/Hoping, Catastrophizing, increased Behavioural Activity, Ability to Control Pain and Ability to Decrease Pain [92]. All questions were ranked in magnitude from (0) to (6) (arb.units).The score of each set is the sum of the scores of its individual questions.

Table 2: Procedure for experiments and corresponding time allocation

Time (min)	Task	Pain Measures	Cardiovascular Measures
5	Read information sheet
10	- Height/Weight measurement - Questionnaires		Blood Pressure & Heart Rate
10	Rest		Blood Pressure & Heart Rate
2	Cold Pressor Task 1	VAS	Blood Pressure & Heart Rate
5	Rest	SF-MPQ
2	Distraction Phase: Cold Pressor Task 2	VAS	Blood Pressure & Heart Rate
5	Rest	SF-MPQ
2	Cold Pressor Task 3	VAS	Blood Pressure & Heart Rate
5	Rest	SF-MPQ
7	Forearm Muscle Ischemia Task	VAS	Blood Pressure & Heart Rate
5	Rest	SF-MPQ
10	Rest		Blood Pressure & Heart Rate

Data reduction and analysis

Statistical analysis of data was performed on SPSS 12.0.1 for Windows (Statistical Package for Social Sciences; LEAD Tech.).

The individual scores of all the components of the SF-MPQ were added together for separate analysis.

Mean Clinical Blood Pressure was calculated by averaging the three Blood Pressure measurements taken before the start of testing.

Blood Pressure measurements taken in each task were also averaged to determine the Mean Experimental Blood Pressure.

Analysis of categorical variables in the three blood pressure groups was achieved by performing Chi-square tests. These analyses included the difference in age, smoking habits and family history of hypertension. Numeric variables were assessed by performing univariate and multivariate analysis of variance (ANOVA) tests on SPSS General Linear Model. A Multivariate ANOVA test was performed to investigate possible differences among the three blood pressure groups in the scores of the questionnaires TAI, SAI, PCS, CSQ and SF-MPQ: {Blood pressure groups (Control, Borderline, Hypertensive)} was set as the �Fixed Factor� and the questionnaires scores were set as the �Dependant Variables�. To analyse the individual scores of the different components of the CSQ, a multivariate ANOVA test was performed by setting {Blood pressure groups (Control, Borderline, Hypertensive)} as �Fixed Factors� and the different components of CSQ �Dependant Variables�. The same principle was applied in the analysis of the different components of the SF-MPQ. In all ANOVA and Chi-square tests the p value was used to assess significance. (p< .01 indicates significance).

We calculated the difference between consecutive SBP/DBP measurements in each task by subtracting each SBP/DBP measurement from its corresponding following one. To find out how blood pressure response changed among the Control, Borderline and Hypertension groups throughout the experiments we performed a multivariate ANOVA on the {Blood pressure groups (C, B, H)} against the {Differences between successive SBP/DBP measurements}.

Bivariate two-tailed Correlation analyses were performed to determine how variables are related. Pearson's correlation coefficient (r) was used to assess the significance of correlation. The correlation was considered significant when r < .01.

Results

Characteristics of the three blood pressure groups

Following data analysis we noticed a significant difference in mean age only between the Control group and Hypertensive group with the later being relatively older, p = .02. (See table 1). No significant difference in smoking habits, family history of hypertension, gender variation or mean age of men and women was found in the three groups.

Control group had lower mean BMI compared to Borderline group, p = .03 and compared to Hypertensive group, p = .02.

TAI and SAI scores: Control group had lower mean TAI scores than the other two groups. There was a significant difference in mean TAI scores between Control group and Borderline group, p = .01 and between Control group and Hypertension group, p = .05. Also, Control group had lower mean SAI scores than Borderline group, p = .02. This means that the anxiety levels were higher in Borderline and Hypertensive groups compared to Control group.

No significant variability in the mean scores of the Pain Catastrophizing Scale and all the different components of the Coping Strategies Questionnaire were found among the three blood pressure groups.

We analysed the difference in ambulatory blood pressure measurements between the three groups. Results showed significant differences between all three groups in mean ambulatory SBP, p < .001 and ambulatory DBP, p < .001. (See table 3)

Table 3: Mean Ambulatory Systolic (SBP) and Diastolic (DBP) day blood pressure in Control (C), Borderline (B) and Hypertension (H) group.

Groups:

Hypertensive, Normotensive, Borderline

Mean Systolic/Diastolic Ambulatory Blood Pressure (mmHg)

Std. Error

Ambulatory Day SBP

B

138.8

2.4

C

120.3

2.3

H

149.7

1.9

Ambulatory Day DBP

B

90.1

2.1

C

76.1

2.0

H

98.5

1.6

Clinical vs. Ambulatory Blood Pressure: Mean Clinical SBP and mean Clinical DBP were correlated to the corresponding Ambulatory SBP and DBP respectively in all subjects to test for any difference between Baseline and Ambulatory Blood Pressure measurements. Results revealed significant correlations for both Systolic Blood Pressure, r = .80, p < .001 and Diastolic Blood Pressure, r = .74, p < .001. This confirmed the classification of the three blood pressure groups and eliminated any major variations in individual blood pressure levels in subjects.

In each task we analysed the following variables in the three different groups: (i) the maximum time tolerated (The Pain Tolerance Time in CPT_1,_2 and _3 and Forearm Muscle Ischemia will be referred to as PTT_1, _2 and _3 and PTT_Ischemia respectively). (ii) the subscale scores of the SF-MPQ for each task (Sensory Pain Rating index (SPR), Affective Pain Rating index (APR), Present Pain Rating index (PPR), and Visual Analogue Scale (VAS) (iii) the arithmetic difference between successive Systolic Blood Pressure (SBP) measurements in each task and (iv) the arithmetic difference between successive Diastolic Blood Pressure (DBP) measurements in each task. The results are illustrated in the tables and graphs below.

Cold Pressor Task 1 results

We analysed mean Pain Tolerance Time (PTT) for the three blood pressure groups. Control group had the lowest mean PPT and Hypertensive group had the highest. PTT in Borderline group was intermediate between the other 2 groups (See table4 & Fig. 4.1). Pain rating results in the SF-MPQ revealed that mean VAS scores and mean PPI scores were lowest in Borderline group, intermediate in Hypertensive group and highest in Control group. Significant difference in VAS scores was noticed between Control group and Borderline group, p = .03. Mean SPR scores were highest in Control group, intermediate in Borderline group and lowest in Hypertension group. Significance values were present between Control group and Hypertension group, p = .01. Mean APR scores were equal in Borderline and Hypertension groups and both lower than the scores of Control group. (See table 5)

Cold Pressor Task 2 results

Distraction was introduced in Cold Pressor 2. Pain Tolerance in this task remained lowest in Control group. It also increased notably in both Control and Borderline groups relative to the first task. Distraction therefore did affect tolerance time in those two groups. Hypertension group tolerance time did not differ from the previous task. VAS and PPI scores retained the pattern seen in the previous task: Controls group had the highest pain rating and Borderline group had the lowest (Significant difference was seen between Control and Borderline p=.02. between). Total Pain Rating scores were also significantly higher in Control subjects relative to the other two groups (Significant difference between Control and Borderline p = .04 and between Control and Hypertension groups p =.004). The notable difference in this task is the increase in pain tolerance time in Borderline and Control groups.

Cold Pressor Task 3 results

In Cold Pressor 3 distraction was removed. Pain Tolerance Time was still lowest in Control group although it was higher relative to the previous task. In Borderline group tolerance time was almost similar to the previous task. In hypertension group, the tolerance time was very close to the previous two tasks. (See table 4 & Fig.3 for Pain Tolerance Time). A notable and significant difference in PPI was noted between Control and Borderline groups p = .009.

VAS and PPI scores were still highest in Control group and lowest in Borderline. Generally speaking the magnitude of scores for each group did not differ considerably from the previous task. Again, it is notable that the tolerance time for Control group is still the lowest and their pain reports are significantly higher than the other two groups.

Forearm Muscle Ischemia Task results

In Forearm Muscle Ischemia Task (FMIT) the results of pain tolerance time (fig 4.2), Present Pain Intensity, Sensory Pain Rating and Total Pain Rating were almost similar in the three blood pressure groups. Only the VAS scores (table 5) were significantly higher in Control group than the other two groups. The individual analysis of scores in the SF-MPQ in FMIT resulted in confusing patterns of distribution that could not be tracked or interpreted.

When we added all the scores in the SF-MPQ together and compared them in the three BP groups we noticed that: SF-MPQ pain scores were highest in Control group and lowest in Borderline group throughout the Cold Pressor and Ischemia Tasks with a significant difference between those two groups in the first Cold Pressor Task, p = .03, and the second CPT, p = .01. (Table 10 & Fig.7)

Table 4: Mean Pain Tolerance Time (PTT) for Control (C), Borderline (B) and Hypertension (H) groups in Cold Pressor Task and Forearm Muscle Ischemia

	*Groups:* *Hypertensive, Normotensive, Borderline*	*Mean Pain Tolerance Time (sec)*	*Std. Error*
PTT_1	C	87.5	9.4
	B	96.7	9.8
	H	106.7	7.6
PTT_2 (Distraction Phase)	C	98.1	6.8
	B	117.5	7.0
	H	107.4	5.5
PTT_3 (Post Distraction Phase)	C	104.0	6.3
	B	119.6	6.5
	H	108.9	5.1
PTT_Ischemia	C	274.2	19.5
	B	265.0	20.3
	H	260.1	15.7

Fig 4.1: Mean Pain Tolerance Time for Control (C), Borderline (B) and Hypertension (H) groups (PTT) in Cold Pressor Task (CPT)

We correlated the Pain Tolerance Time data with the total scores of the SF-MPQ for the three BP groups in both experiments. The results revealed a negative correlation which was significant in the three Cold Pressor tasks and in the Ischemia task, (r = -.4, p < .01 in CPT_1), (r = -.6, p < .01 in CPT_2), (r = -.4, p < .01 in CPT_3), (r = -.4, p < .01 in FMIT). This negative correlation was expected and it confirms the negative linear link between Pain Tolerance Time and Pain rating. The longer the pain was tolerated, the lower it was reported and vice versa.

It is notable however that although Borderline group tolerated less time than Hypertension group during the first Cold Pressor Task, their pain report in that task was actually slightly lower where it was expected to be actually higher. However, this may be explained by the fact that the differences in Pain Tolerance Time between the three groups, and the difference in SF-MPQ scores between Borderline and Hypertension groups failed to reach statistical significance.

In every Cold Pressor Task, Systolic and Diastolic BP were taken at 0 sec and 60 sec from the start of each CPT task. In Forearm Muscle Ischemia Task, SBP and DBP measurements were taken at 0, 120 and 240 seconds from the start (after hand exercise ends). We wanted to explore the reaction of Blood Pressure in the three different groups in response to pain in each task. The ANOVA analyses showed that in the three Cold Pressor Tasks the results followed a similar trend in the reaction of both Systolic and Diastolic Blood Pressure in the three groups. Mean SBP and DBP increased during CPT_1, _2 and _3 in all BP groups. This increase was greatest in Hypertensive group, intermediate in Borderline group and lowest in Control group. The rise in blood pressure of Control and Hypertension was group smaller in CPT_2 and became smallest in CPT_3. The opposite however was noticed in Borderline group as results showed that the increase in their blood pressure became more pronounced as they progressed from CPT_1 to CPT_3.

In The Forearm Muscle Ischemia mean SBP and mean DBP in all groups decreased first and then started increasing towards the end of the task; the arithmetic difference between the second and first SBP/DBP measurements yielded negative values. The fact that blood pressure did decrease in response to pain in this task rather than increase contradicts previous findings and is hard to interpret. We assumed therefore that the FMI task in our study was not reliable in the interpretation of blood pressure responses to pain. The ANOVA results were not significant except for the difference in SBP in CPT_1 compared between Control and Borderline groups, p = .01. (See table 11& Fig.8, 9)

To examine any possible relationship between the experimental blood pressure measurements on one side and Pain Tolerance Time and scores taken during each task on the other side, we performed the following two-tailed correlations: (i) Correlation between mean systolic blood pressure and mean Pain Tolerance Time in each task. (ii) Individual Correlations between mean systolic blood pressure and corresponding mean VAS, PPI, SPR, APR and TPR scores in each task. We also repeated the same correlations with mean Systolic Blood Pressure instead of Diastolic BP. the results revealed positive correlation between blood pressure (systolic and diastolic) and Pain Tolerance Time, and negative correlation between blood pressure (systolic and diastolic) and all pain scores of VAS, PPI, SPR, APR and TPR. Although all these correlations failed to reach statistical significance - even after outliers were eliminated from the data � the outcome was nevertheless expected. These results confirm that blood pressure and pain rating feedback increase linearly as the magnitude of the stressful stimulus intensifies and that this relationship is independent of the blood pressure group.

Research on humans and animals confirmed the link between hypoalgesia and high blood pressure or (hypertension)^{3 4 5 6 7 8 9 13 14 15 16}. Many theories have been proposed to explain the phenomenon of hypertensive hypoalgesia, but until today the exact underlying mechanism remains uncertain. Nonetheless, most studies investigating the link between blood pressure and hypoalgesia seem to support the idea that decreased pain perception is associated with chronic high blood pressure and is not affected by daily fluctuations in blood pressure levels ^{21 22 23}. The majority of the previous studies were conducted on two different blood pressure groups, Normotensive and Hypertensive subjects; various forms of pain stimuli were used and direct comparisons of the responses to pain were carried out in order to draw experimental conclusions.

Pain perception in subjects with Borderline hypertension was also investigated in many studies and compared with the results of normotensive and hypertensive subjects. All those studies confirmed that Borderline hypertensive individuals have lower pain perception when compared to normotensive individuals. Only one study by Ghione et al.¹³ investigated pain thresholds in three blood pressure groups at the same time (Normotensive, Borderline and Hypertensive) and found that although pain threshold in Borderline hypertensive subjects was higher than that of normotensive subjects, Borderline and established Hypertensive subjects had similar sensory pain thresholds. However, the study by Ghione et al only assessed the sensory-discriminative aspect of pain and did not investigate the affective and cognitive-evaluative aspect of that pain. Furthermore, Ghione et al did not investigate the blood pressure reactivity to the stressful stimulus and they drew their conclusions from using only one type of stimulus, the tooth pulp stimulation technique.

In fact, there is a growing interest in studying the physiological responses to stressful stimuli in Borderline hypertension individuals in order to gain more knowledge on their pathophysiology and prognosis. It is of great importance to ultimately determine whether it is clinically useful to adopt antihypertensive drug therapy in Borderline patients in the same way as in patients with established hypertension. If the clinical and physiological behaviour (such as response to pain and corresponding cardiovascular reactivity) of Borderline hypertension patients is similar to established hypertension patient, it may only be a matter of time before the former progress from being Borderline to become established hypertensives. In this case, it may be useful to start drug therapy as soon as borderline hypertension is diagnosed. However, if Borderline individuals respond to stress and physiologically react in a way that is comparable or close to the response of normotensive individuals, it may be worthwhile maintaining the current guidelines of treatment i.e. lifestyle change advice and one year of clinical monitoring.

For all those reasons and to have a clearer view on the behavioural and cardiovascular responses to pain in Borderline hypertension subjects, and to establish a more comprehensible comparison between normotensives, Borderline and hypertensive subjects we conducted this study on those three blood pressure groups.

In all Cold Pressor Tasks pain tolerance time was always lowest in normotensive subjects compared to Borderline and hypertensive subjects. Distraction in Cold Pressor 2 did influence normotensive and Borderline subjects whose tolerance time continued to increase in Cold Pressor 3 even after the distraction was removed. Distraction however did not affect hypertensive subjects whose tolerance time remained relatively unchanged before, during and after distraction (Cold Pressor Task 1, 2 and 3 respectively). The adaptability to pain or the modulation of painful stimuli was therefore a common feature in Borderline and normotensive individuals only. This conclusion however must be regarded carefully as the differences in time tolerance in the three CP tasks were not statistically significant.

In the Forearm Muscle Ischemia Task Pain Tolerance Time did not vary considerably enough to generate any plausible conclusions.

In contrast with the Pain Tolerance Time which represents a reactive and discriminative response to pain, the SF_MPQ measures the subjective assessment (evaluative and affective) of the quality and quantity of pain.

When we considered the sum of scores of all components of the SF-MPQ for each Cold Pressor task, we noticed that Borderline hypertensive subjects reported the intensity of pain they experienced in a less dramatic way compared to normotensive and hypertensive subjects. However, when the different aspects and qualities of pain were described, Borderline subjects seem to have perceived pain in an intermediate way between hypertensive and normotensive subjects. Although the variations between pain scores were not always significant statistically, a unique behavioural pattern was noticed characteristic of each blood pressure group. The SF-MPQ results in Forearm Muscle Ischemia Task were neither statistically significant nor they did follow a specific pattern that can enable us to draw a plausible conclusion.

When we correlated the sum of scores of all components of the SF-MPQ with their corresponding Pain Tolerance Time for the three BP groups in Cold Pressor Task and Forearm Muscle Ischemia Task there was a strong negative correlation. This means that the longer the tolerance time in a task the lower were the pain rating and description scores. In other words, the description of pain quantity and quality reflects the tolerance time of that pain in all three groups. It is not surprising therefore that the sum of SF-MPQ scores obtained were highest during the first Cold Pressor Task in all three groups just like the Pain Tolerance Time. The pattern of distribution of scores in the SF-MPQ for each group reflected the Pain Tolerance Time of that group: In normotensive subjects, the pain scores decreased significantly during the distraction phase and remained on that level in the third Cold Pressor Task (post-distraction). Hypertensive and Borderline subjects reported their worst pain during the first task, and then reported significantly less pain during the second task and finally slightly higher pain than the second report in the third task (post-distraction).

The overall results of pain perception analysis seem to confirm that :(i) In comparison to normotensive subjects, Borderline hypertensive subjects had more pain tolerance (lower pain perception). This is in line with the previous findings of the studies which compared pain perception in normotensives and Borderline hypertensives ^{9 13 7 21} (ii) Pain tolerance time and pain description were positively related but not necessarily proportional to each other. (iii) Distraction from pain had a dramatic effect on Borderline and normotensive subjects which enabled them to tolerate pain more like subjects with established hypertension. These results are also supportive of previous findings.^{40
41 42 43 45} (iv) This effect of distraction remained present in Borderline and normotensive subjects even after distraction was removed. (v) Pain rating in Borderline subjects was closer to that of hypertensive subjects.

Blood pressure (systolic and diastolic) increased in each task in all three BP groups as the degree of pain augmented. This is in line with previous findings which confirm the linear relationship between pain intensity and Blood pressure increase[93]. When we compared this increase between the three groups in the Cold Pressor Task experiment we found that in normotensive subjects the increase was the lowest among the three groups in CPT_1, _2 and _3 although it became less pronounced in CPT_2 (during distraction) and then diminished further in CPT_3 (after distraction). The increase in SBP and DBP in Hypertension subjects was the highest among the three groups, and it also diminished as we progressed from CPT_1 to CPT_3. In Borderline hypertensives however, the increase in systolic and diastolic blood pressure was intermediate compared to Normotensives and Hypertensives and it became slightly higher as we progressed from CPT_1 to CPT_3. Again, the blood pressure increase in Borderline hypertensive subjects was intermediary between the increase in blood pressure seen in Normotensives and the one seen in Hypertensives. This aspect of cardiovascular reactivity was therefore a unique characteristic of Borderline group which was intermediate in comparison to the other two groups.

Blood pressure measurements in all tasks were negatively correlated with pain rating and description scores of the SF-MPQ and positively correlated with Pain Tolerance Time. These results also confirm previous findings that subjects with higher blood pressure do tolerate pain more and report pain less when compared with subjects that have lower blood pressure.^{2 3 5 13 15}

It is also important to mention that this study was the first to examine the effect of distraction on pain perception in Borderline hypertension subjects. Also, it was the first to compare both pain tolerance and pain perception in normotensive, borderline hypertensive and established hypertensive subjects before, during and after distraction. Although the sample size in this study was not big enough which made data unsuitable for statistical analysis at certain points, the results did generate robust patterns that can be experimentally evaluated.

Possible improvements on the currents study and recommendations for future studies

Some improvements and refinements in the protocol of both experiments should be considered in future studies in order to obtain more significant results:

Testing took place in an open area in the clinic where noise pollution varied from time to time during the day. Too much noise is a source of distraction for the Cold Pressor Task and can interfere with the results of pain rating and tolerance as discussed above. A private and noise free area would be better as a location for our experiment than the open area we used.

Also in the CPT, pain rating and tolerance values can be affected by the different attitudes towards cold which varies among individuals. People whose jobs or careers involve handling ice, cold water, freezers or even cold merchandise for long periods during the day can become habituated to cold sensations and would not perceive cold water in the same way as other individuals whose daily activities involve minimal contact with cold objects irrespective of the other factors that affect pain perception. Among our participants, those who are accustomed to cold would report lower pain ratings and have longer tolerance time in the CPT than participants who are not. It would be sensible therefore to take this factor into consideration in future studies and include a question in the screening sheet about the nature of job the participant and include this in the final data analysis. Also, the same study should be replicated with different kinds of stimuli that can be electrical, mechanical or thermal and results can be compared to the current study.

The Omron blood pressure monitor did occasionally give erroneous readings. Although this was rare (about 1 in 70 readings) it should be nonetheless mentioned. Wrong readings can be avoided by minimizing arm movements when the cuff is inflating.

In the clinical screening before the experiments the participants who are smokers were not asked if they did smoke immediately before they came to the clinic. Resting blood pressure and resting heart rate rise immediately after smoking[94] . This fact would influence those measures clinically and experimentally within 30 to 60 seconds after smoking. Restrictions on smoking immediately before the experiment should be included in future protocols.

Female participants were not asked whether they are using contraceptive pills at the time of the study. Some contraceptive pills especially the ones that contain Progesterone are known to increase resting blood pressure in women who use them regularly[95]. This will affect experimental blood pressure readings in our experiment. A query on any possible usage of contraceptive pills in female participants should be added to the screening sheet in similar future studies

In the second experiment (the Forearm Muscle Ischemia Task) results were difficult to interpret as they did not generally show a clear trend of difference between the three groups. We think that the reason for this is the difference in the contraction load among subjects. Every participant in this experiment had to perform 50% of his/her maximum voluntary contraction. Results could be more constructive if the contraction load was unified for all participants. The same experiment could be repeated with a single contraction load for all participants.

Body Mass Index and State and Trait Anxiety were higher in Borderline and Hypertension subjects compared to normotensives. A positive correlation between Body Mass Index and blood pressure has been well documented[96] [97] [98]. Also, anxiety levels are known to negatively affect pain tolerance, and raise resting blood pressure^{78 78 80 81 83 85}. The possible influence of those two factors on increased blood pressure reactivity and the response to pain in Borderline and Hypertension groups should not be eliminated.

This study will need to be taken further if we want to confirm the current findings and elaborate more on the behavioral and clinical characteristics of Borderline hypertensive subjects and on their pathological progression. A follow-up study using the same experiments we used should be carried out in the future on the participants who progress from borderline to established hypertension and compare the results of the two studies together.

Conclusion: This study confirms that Borderline hypertensive subjects tolerate and rate pain more like subjects with established hypertension, yet they still have pain related physiological features that are characteristics of normotensives; we found that distraction can alter pain tolerance in normotensives and Borderline hypertensives but not in established hypertensives. We also found that the cardiovascular reactivity in Borderline hypertensives is intermediate between that of normotensives and established hypertensives. In a clinical sense, the findings in this study suggest that although Borderline hypertensives do not respond to pain quite like normotensives, they may still be prevented from progressing from Borderline to established hypertension and regain normotensive status. Borderline hypertensives may indeed respond positively to intensive lifestyle intervention in the effort to reduce their risk in developing established Hypertension.

Acknowledgements: Dr Una Martin, Dr Christopher Ring, Dr Louisa Edwards, Sister Louise Beesley, Dr Abdullah Shehab and the staff at the Wellcome Trust Clinical Research Facility. A special �Thank You� for your help and assistance in the effort of making this study successful.

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Appendix A

SAI (State Anxiety Inventory) ⁸⁶

DIRECTIONS: Please read the statements below and then circle the number that corresponds with how you feel right now, that is at this moment. There are no right or wrong answers. Use the following scale:

1 = Not at all

2 = Somewhat

3 = Moderately

4 = Very Much

1. I feel calm	1 2 3 4
2. I feel secure	1 2 3 4
3. I am tense	1 2 3 4
4. I am regretful	1 2 3 4
5. I feel at ease	1 2 3 4
6. I feel upset	1 2 3 4
7. I am presently worrying over possible misfortunes	1 2 3 4
8. I feel rested	1 2 3 4
9. I feel anxious	1 2 3 4
10. I feel comfortable	1 2 3 4
11. I feel self-confident	1 2 3 4
12. I feel nervous	1 2 3 4
13. I am jittery	1 2 3 4
14. I feel �high strung�	1 2 3 4
15. I am relaxed	1 2 3 4
16. I feel content	1 2 3 4
17. I am worried	1 2 3 4
18. I feel over-excited and �rattled�	1 2 3 4
19. I feel joyful	1 2 3 4
20. I feel pleasant	1 2 3 4

TAI (Trait Anxiety Inventory) ⁸⁶

DIRECTIONS: Please read the statements below and then circle the number that corresponds with how you generally feel. There are no right or wrong answers. Use the following scale:

1 = Not at all

2 = Somewhat

3 = Moderately

4 = Very Much

1. I feel pleasant	1 2 3 4
2. I tire quickly	1 2 3 4
3. I feel like crying	1 2 3 4
4. I wish I could be as happy as others seem to be	1 2 3 4
5. I am losing out on things because I can�t make up my mind soon enough	1 2 3 4
6. I feel rested	1 2 3 4
7. I am �calm, cool and collected�	1 2 3 4
8. I feel that difficulties are piling up so that I cannot overcome them	1 2 3 4
9. I worry too much over something that doesn�t really matter	1 2 3 4
10. I am happy	1 2 3 4
11. I am inclined to take things hard	1 2 3 4
12. I lack self-confidence	1 2 3 4
13. I feel secure	1 2 3 4
14. I try to avoid facing a crisis or difficulty	1 2 3 4
15. I feel blue	1 2 3 4
16. I am content	1 2 3 4
17. Some unimportant thoughts run through my mind and bother me	1 2 3 4
18. I take disappointments so keenly that I can�t put them out of my mind	1 2 3 4
19. I am a steady person	1 2 3 4
20. I get in a state of tension or turmoil as I think over my recent concerns and interests	1 2 3 4

CSQ (Coping Strategies Questionnaire)⁹²

Directions: As normal, healthy people go through their typical day they experience pain from time to time. This pain might be due to a toothache, an occasional headache or a minor injury such as a cut or a bruise. People cope or deal with such common pain problems in different ways. These include saying things to themselves when they experience pain or engaging in different activities. Below is a list of things that people have reported doing when they feel pain. For each activity, I want you to indicate, using the scale below, how much you engage in that activity when you feel pain.

When I feel pain....
1.	I try to feel distant from the pain, almost as if the pain was in somebody else's body.	?	�	?	?	?	?	?
2.	I leave the house and do something, such as going to the movies or shopping.	?	�	?	?	?	?	?
3.	I try to think of something pleasant.	?	�	?	?	?	?	?
4.	I don't think of it as pain but rather as a dull or warm feeling.	?	�	?	?	?	?	?
5.	It is terrible and I feel it's never going to get any better.	?	�	?	?	?	?	?
6.	I tell myself to be brave and carry on despite the pain.	?	�	?	?	?	?	?
7.	I read.	?	�	?	?	?	?	?
8.	I tell myself that I can overcome the pain.	?	�	?	?	?	?	?
9.	I count numbers in my head or run a song through my mind.	?	�	?	?	?	?	?
10.	I just think of it as some other sensation, such as numbness.	?	�	?	?	?	?	?
11.	It is awful and I feel that it overwhelms me.	?	�	?	?	?	?	?
12.	I play mental games with myself to keep my mind off the pain.	?	�	?	?	?	?	?
13.	I feel my life isn't worth living.	?	�	?	?	?	?	?
14.	I know someday someone will be here to help me and it will go away for a while.	?	�	?	?	?	?	?

15.	I pray to God it won't last long.	?	�	?	?	?	?	?
16.	I try not to think of it as my body, but rather as something separate from me.	?	�	?	?	?	?	?
17.	I don't think about the pain.	?	�	?	?	?	?	?
18.	I try to think years ahead, what everything will be like after I've gotten rid of the pain.	?	�	?	?	?	?	?
19.	I tell myself it doesn't hurt.	?	�	?	?	?	?	?
20.	I tell myself I can't let the pain stand in the way of what I have to do.	?	�	?	?	?	?	?
21.	I don't pay any attention to the pain.	?	�	?	?	?	?	?
22.	I have faith in doctors that someday there will be a cure for my pain.	?	�	?	?	?	?	?
23.	No matter how bad it gets, I know I can handle it.	?	�	?	?	?	?	?
24.	I pretend it's not there.	?	�	?	?	?	?	?
25.	I worry all the time about whether it will end.	?	�	?	?	?	?	?
26.	I replay in my mind pleasant experiences in the past.	?	�	?	?	?	?	?
27.	I think of people I enjoy doing things with.	?	�	?	?	?	?	?
28.	I pray for the pain to stop.	?	�	?	?	?	?	?
29.	I imagine that the pain is outside of my body.	?	�	?	?	?	?	?
30.	I just go on as if nothing happened.	?	�	?	?	?	?	?
31.	I see it as a challenge and don't let it bother me.	?	�	?	?	?	?	?
32.	Although it hurts, I just keep on going.	?	�	?	?	?	?	?
33.	I feel I can't stand it anymore.	?	�	?	?	?	?	?
34.	I try to be around other people.	?	�	?	?	?	?	?

35.	I ignore it.	?	�	?	?	?	?	?
36.	I rely on my faith in God.	?	�	?	?	?	?	?
37.	I feel like I can't go on.	?	�	?	?	?	?	?
38.	I think of things I enjoy doing.	?	�	?	?	?	?	?
39.	I do anything to get my mind off the pain.	?	�	?	?	?	?	?
40.	I do something I enjoy, such as watching TV or listening to music.	?	�	?	?	?	?	?
41.	I pretend it's not a part of me.	?	�	?	?	?	?	?
42.	I do something active, like household chores or projects.	?	�	?	?	?	?	?

Based on all the things you do to cope, or deal with your pain, on an average day, how much control do you feel you have over it? Please blacken the appropriate number.

�

No control

Almost no control

Little control

Some control

A lot of control

Almost complete control

Complete

control

Based on all the things you do to cope, or deal with your pain, on an average day, how much are you able to decrease it? Please blacken the appropriate number.

?	�	?	?	?	?	?
Can�t decrease it at all	Can�t decrease it much	Can decrease it a little	Can decrease it somewhat	Can decrease it a lot	Can decrease it almost completely	Can decrease it completely

PCS (Pain Catastrophizing Scale) ⁹⁰

Everyone experiences painful situations at some point in their lives. Such experiences may include headaches, tooth pain, joint or muscle pain. People are often exposed to situations that may cause pain such as illness, injury, dental procedures or surgery.

We are interested in the types of thoughts and feelings that you have when you are in pain. Listed below are thirteen statements describing different thoughts and feelings that may be associated with pain. Using the following scale, please indicate the degree to which you have these thoughts and feelings when you are experiencing pain.

0 = not at all

1 = to a slight degree

2 = to a moderate degree

3 = to a great degree

4 = all the time

When I�m in pain�

1. I worry all the time about whether the pain will end.	0 1 2 3 4
2. I feel I can�t go on.	0 1 2 3 4
3. It�s terrible and I think that it�s never going to get any better.	0 1 2 3 4
4. It�s awful and I feel that it overwhelms me.	0 1 2 3 4
5. I feel I can�t stand it any more.	0 1 2 3 4
6. I become afraid that the pain will get worse.	0 1 2 3 4
7. I keep thinking of other painful events.	0 1 2 3 4
8. I anxiously want the pain to go away.	0 1 2 3 4
9. I can�t seem to keep it out of my mind.	0 1 2 3 4
10. I keep thinking about how much it hurts.	0 1 2 3 4
11. I keep thinking about how badly I want the pain to stop.	0 1 2 3 4
12. There�s nothing I can do to reduce the intensity of the pain.	0 1 2 3 4
13. I wonder whether something serious may happen.	0 1 2 3 4

SF-MPQ (Short Form McGill Pain Questionnaire) ⁷⁷

Using the visual analogue scale below, please give the number that best describes your peak pain during the previous assessment: _______

JUST NOTICEABLE

PAIN WORST

NO �-----------------------------3-----------------------------� POSSIBLE

PAIN 0 50 100 PAIN

Which word best describes your peak pain during the previous assessment?

______ No pain

______ Mild

______ Discomforting

______ Distressing

______ Horrible

______ Excruciating

The following 15 words are used to describe pain. Rate the extent to which each word describes your peak pain experience during the previous assessment.


1.	THROBBING	?	�	?	?
2.	SHOOTING	?	�	?	?
3.	STABBING	?	�	?	?
4.	SHARP	?	�	?	?
5.	CRAMPING	?	�	?	?
6.	GNAWING	?	�	?	?
7.	HOT-BURNING	?	�	?	?
8.	ACHING	?	�	?	?
9.	HEAVY	?	�	?	?
10.	TENDER	?	�	?	?
11.	SPLITTING	?	�	?	?
12.	TIRING-EXHAUSTING	?	�	?	?
13.	SICKENING	?	�	?	?
14.	FEARFUL	?	�	?	?
15.	PUNISHING-CRUEL	?	�	?	?

Luc Jaber

	*Groups:* *Hypertensive, Normotensive, Borderline*	*Mean Visual Analogue Scale scores (arb. Units)*	*Std. Error*
	*Groups:* *Hypertensive, Normotensive, Borderline*	*Mean Visual Analogue Scale scores (arb. Units)*	*Std. Error*
VAS_1	C	79.1	5.8
	B	60.8	6.0
	H	74.9	4.7
VAS_2 (Distraction Phase)	C	76.5	6.3
	B	54.6	6.5
	H	66.8	5.1
VAS_3 (Post Distraction)	C	76.9	7.3
	B	57.5	7.6
	H	69.0	5.9
VAS_Ischemia	C	72.3	6.5
	B	59.2	6.8
	H	70.9	5.3

	*Groups:* *Hypertensive, Normotensive, Borderline*	*Mean Present Pain Intensity scores (arb. Units)*	*Std. Error*
PPI_1	C	3.0	.29
	B	2.3	.30
	H	2.8	.23
PPI_2 (Distraction Phase)	C	3.4	.31
	B	2.0	.32
	H	2.4	.25
PPI_3 (Post Distraction)	C	3.2	.33
	B	1.9	.35
	H	2.5	.27
PPI_Ischemia	C	2.7	.37
	B	2.9	.39
	H	2.7	.30

	*Groups:* *Hypertensive, Normotensive, Borderline*	*Mean Sensory Pain Rating scores* *(arb. Units)*	*Std. Error*
SPR_1	C	13.3	1.7
	B	9.3	1.8
	H	7.5	1.4
SPR_2 (Distraction Phase)	C	14.1	1.8
	B	8.9	1.9
	H	7.0	1.4
SPR_3 (Post Distraction)	C	13.9	2.2
	B	10.0	2.3
	H	9.0	1.8
SPR_Ischemia	C	13.5	2.4
	B	13.0	2.5
	H	12.3	1.9

	*Groups:* *Hypertensive, Normotensive, Borderline*	*Mean Affective Pain Rating scores (arb. Units)*	*Std. Error*
APR_1	C	2.5	.51
	B	1.5	.53
	H	1.5	.41
APR_2 (Distraction Phase)	C	2.3	.48
	B	1.1	.50
	H	1.1	.39
APR_3 (Post Distraction)	C	2.6	.52
	B	1.2	.54
	H	1.3	.42
APR_Ischemia	C	2.5	.76
	B	3.2	.79
	H	1.8	.61

	*Groups:* *Hypertensive, Normotensive, Borderline*	*Mean Total Pain Rating scores (arb. Units)*	*Std. Error*
TPR_1	C	15.9	2.0
	B	10.8	2.1
	H	9.0	1.6
TPR_2 (Distraction Phase)	C	16.4	2.1
	B	10.0	2.2
	H	8.2	1.7
TPR_3 (Post Distraction)	C	16.5	2.5
	B	11.2	2.6
	H	10.3	2.0
TPR_Ischemia	C	15.9	2.9
	B	16.2	3.1
	H	14.1	2.4

Hypertensive: (H) Normotensive/control: (C) Borderline: (B)	Male, Female	Mean Age	Std. Deviation	N
B	F	37.75	6.946	4
	M	41.75	4.924	4
	*Total*	*39.75*	*5.970*	8
C	F	36.00	10.354	6
	M	32.60	11.610	5
	*Total*	*34.45*	*10.520*	11
H	F	39.33	9.849	9
	M	46.36	12.460	11
	*Total*	*43.20*	*11.638*	20

	*Groups:* *Hypertensive, Normotensive, Borderline*	*Mean Systolic/Diastolic Ambulatory Blood Pressure (mmHg)*	*Std. Error*
Ambulatory Day SBP	B	138.8	2.4
	C	120.3	2.3
	H	149.7	1.9
Ambulatory Day DBP	B	90.1	2.1
	C	76.1	2.0
	H	98.5	1.6

	*Groups:* *Hypertensive, Normotensive, Borderline*	Mean total of all McGill scores (arb. Units)	Std. Error
Sum of all McGill scores In CPT_1	C	111.385	8.684
	B	83.333	9.038
	H	94.250	7.001
Sum of all McGill scores In CPT_2	C	96.308	7.950
	B	66.583	8.274
	H	77.500	6.409
Sum of all McGill scores In CPT_3	C	96.692	9.558
	B	70.667	9.948
	H	81.950	7.706

	*Blood Pressure Groups (Control, Borderline, Hypertensive)*	*Mean Difference between successive SBP/DBP measurements*	*Std. Error*
Difference between 2^nd & 1^st SBP *CPT_1*	C	7.000	4.026
	B	7.875	3.487
	H	16.455	2.973
Difference between 2^nd & 1^st DBP *CPT_1*	C	14.167	4.454
	B	15.000	3.858
	H	20.273	3.290
Difference between 2^nd & 1^st SBP *CPT_2*	C	6.000	4.792
	B	8.250	4.150
	H	11.273	3.539
Difference between 2^nd & 1^st DBP *CPT_2*	C	-1.333	2.742
	B	4.875	2.375
	H	6.364	2.025
Difference between 2^nd & 1^st SBP *CPT_3*	C	4.333	3.807
	B	9.125	3.297
	H	11.091	2.812
Difference between 2^nd & 1^st DBP *CPT_3*	C	11.167	5.577
	B	12.375	4.829
	H	13.727	4.119
Difference between 2^nd & 1^st SBP *FMIT*	C	-6.500	6.049
	B	-7.125	5.239
	H	-1.818	4.468
Difference between 2^nd & 1^st DBP *FMIT*	C	-.833	3.976
	B	-3.000	3.443
	H	2.182	2.936
Difference between 3^rd & 2^nd SBP *FMIT*	C	-.667	5.119
	B	1.125	4.433
	H	2.455	3.781
Difference between 3^rd & 2^nd DBP *FMIT*	C	-4.000	2.461
	B	1.000	2.132
	H	-1.818	1.818

Fig 1: Framingham Study 51

Appendix A

SAI (State Anxiety Inventory) 86

TAI (Trait Anxiety Inventory) 86

When I�m in pain�

Fig 1: Framingham Study ⁵¹

SAI (State Anxiety Inventory) ⁸⁶

TAI (Trait Anxiety Inventory) ⁸⁶