Pressure Pain Threshold Values Obtained Through Algometers

Pain intensity can provide relevant medical information; nowadays, pain measuring is still subjective; therefore, there are efforts to develop devices to measure the intensity of painful stimuli objectively. A review of the scientific literature on pressure pain obtained through algometers is carried out in this work. This literature review aims to present a database of pain pressure thresholds (PPT) related to different body parts so that future research on PPT, using an algometer, could compare their results against this research. The results of these PPT values are presented and grouped according to the body regions where previous researchers recorded their results to where they applied the pressure- trapezius muscles, back muscles, upper extremities, leg muscles, foot area, and muscles of the head. These values can be considered a reference to evaluate new algometers' accuracy and reliability. Finally, the algometers operational parameters range are defined according to all the studied algometers.


INTRODUCTION
The International Association for the Study of Pain (IASP) [1] defines pain as "an unpleasant sensory and emotional experience associated with tissue damage or is described in terms of damage, whether the damage is real or potential." Since pain has existed throughout human evolution and is considered among the most significant public health problems of our society whether being considered a symptom or a disease [1] ; especially for those people with chronic diseases, physicians have studied and compared different pain types through scientific research and experimentation in order to generate knowledge [2] .
According to records, there are several pain classifications concerning intensity, frequency, or origin, even though there is scarce information regarding the threshold for a stimulus to become a pain sensation.
According to its origin, the pain can be nociceptive or neuropathic; therefore, measuring its intensity can provide information about its origin. However, doctors usually use a subjective scale to assess the pain suffered by a patient; based on this scale, the type and frequency of analgesics prescribed are determined.
Pain intensity determines the patient's treatment pathway and goals; pain can become a cause of disability for the patient depending on the intensity; therefore, various researchers have directed their efforts to develop devices to measure pain called algometers. Measuring a pressure pain threshold (PPT) is commonly adopted to try to quantify this sensation.
The PPT is currently defined as "the minimum necessary intensity of a nociceptive signal, derived from a pressure stimulus, to be perceived as painful [3] ." Several studies have been dedicated to finding the pain threshold in people, most of them using devices that generate a painful stimulus, like algometers [4] . An algometer is a device used for producing a controlled pain stimulus and can be either manual or electrome-chanical. Studies have shown the feasibility of electromechanical algometers [5] [6] [7] [8] ; nevertheless, these devices are not yet available in a commercial way.
Thus, most of the studies reported in records have adopted manual algometers. Unfortunately, manual algometers cannot maintain a constant stimulus application speed (indentation speed) [7] , and there may be data truncation because of the scales of manual algometers [9] . On the other hand, by using an electromechanical algometer, there is the possibility of normalizing the stimulus, defining the application rate of the stimulus and the penetration distance on the skin of the subject; this, in turn, increases the variables provided by the algometer, and in this way, more data can be obtained for pain analysis.
Despite articles dealing with PPT data, there is no work synthesizing assertive pain threshold values; thus, a literature review has been performed to understand better the problem of measuring a pain sensation. This work reviews the recent literature regarding the PPT values provided by manual and electromechanical algometers concerning different body regions.
This record review aims to present a database of PPTs related to different body parts so that future researchers on PPT, using an algometer, can use this work as a reference.
As a result of reading the scientific records, it was possible to define common characteristics that present electromechanical algometers have. The algometers operational parameters were defined considering all the studied algometers. These characteristics are summarized in the last section of this work and serve as a guideline to develop new electromechanical algometers.

Literature Review methodology
A record research was performed, extracting articles from PubMed and Google Scholar databases to find articles related to PPT and the devices mentioned earlier by using the keywords "pain, pressure pain threshold, pressure algometry, algometer, dolorimeter, electromechanical algometer, and computerized algometer." The search made by using each word separately resulted in 185 selected articles. From these 185 articles, scientific papers published before 2013 were discarded, except for the article [5] , which was included to gain more data about the electromechanical algometers.
Inclusion and exclusion criteria was adopted to select the resulting 75 articles from the original 185. The inclusion criteria considered were the studies with precise results of PPT mean values, studies that used either a manual or an electromechanical pressure algometer, and studies that involved healthy subjects and subjects who suffered some pain or illness. This latter information has also been considered to analyze the differences in PPTs between healthy and ill people. On the other hand, the exclusion criteria adopted were the use of other instruments different from pressure algometers to generate a painful stimulus, studies that do not report the mean PPTs, and studies that do not specify the area of applied stimuli. A total of 20 scientific papers met the inclusion and exclusion criteria and thus were deeply studied and classified according to the body part where the stimulus was appliedtrapezius muscles, back muscles, upper limbs, leg muscles, foot area, and head muscles. Figure 1 shows the article selection process described above and the final cardinality of papers considered for the six body parts mentioned before. As a first outcome of analyzing these 20 articles, the algometers list reported in Table 1 shows the existing models of algometers used in previous works.

Data extraction
The following data were collected and summarized in It is worth mentioning that the PPTs results were recorded when the stimulus changes from being comfortable to being uncomfortable, or a painful sensation was mentioned. Therefore, the PPT results collected from previous works have been obtained in each study as follows: a different number of trials were performed on each subject (varying from 2 to 5 applications of the stimulus), the average value of PPTs per subject was calculated over these trials, and finally, the mean values over all subjects were evaluated and corresponded to the PPT reported in Tables 2-7, for the body part where the stimulus was applied.
All the PPT values were properly converted and reported in the SI unit, kPa. For those studies where any kind of treatment was performed, only the baseline values were taken into account. For example, in FIGURE 1. Flow diagram of the followed methodology in paper selection. [10] , a baseline test was performed and then the subjects received a massage treatment; later on, they underwent another PPT test so, only the values of the first test were included in the tables.
A normalization of measurement units was also necessary for the stimulus application's speed rate (kPa/s) to compare all values shown in this study. As it can be seen the normalization was done for all collected data, except for the data extracted from [7] where the values used are in mm/s (see Table 6). It also shows that the range of speed rates varied from 10 to 126 kPa/s, and that in 5 studies the rate was not specified [8] [10] [11] [12] [13] . It can also be noted that the most used rate is 30 kPa/s (43.75% of the studies), followed by rates of about 124 kPa/s (18.75%), and 50 kPa/s (9.37%).
The age of the subjects involved varied from 18 to 88.
In most studies, subjects were asked to stop taking any pharmaceutical drug (or medicine that alleviated pain) at least 24 hours before the test. Only in [14] were the patients allowed to continue their usual medical treatment during the experiment.
Since some studies conducted tests on different parts of the body, only the body parts that had reported values were included. Therefore, this work only presents the results of the trapezius muscles, back muscles, upper extremities and lower legs and head area. For example, in [15] , a stimulus was applied in the middle trapezius muscle, low back, hand, and quadriceps. The mean values of PPT for each body region are reported in the corresponding table (Tables 2-5).
Most of the algometers considered in the articles were manual. As seen, the Somedic algometer was the most used (10 papers), followed by the Warner algometer (6 papers), while only in one paper [12] were the tests carried out with the Baseline Dolorimeter. Finally, in 6 studies, tests were performed using an electromechanical algometer.
All articles used an algometer with a flat circular tip that varied in size from 0.5 to 2 cm 2 (area of stimulation). In all the studies carried out with an electromechanical algometer, the subjects had an "emergency stop button," Some studies performed with a manual algometer [ [23] in order to record the PPT value.
Finally, the range of intervals between trials varied from 10 s to 300 s, the most used is 30 s, followed by 20 s.

RESULTS AND DISCUSSION
The analysis concerned the body part where the pressure stimulus had been applied; a summary table is populated for each of them.

Characteristics of the electromechanical algometers used in the studies
It was possible to list the adopted algometers from the analysis of the 20 articles selected from the literature which were either manual or electromechanical. These algometers, together with the producer, the model, and the reference for further details are reported in Table 1.
The Algoforce PA3 adopted in [5] has a pressure sensor and an actuator for what concerns the electromechanical ones. This algometer is controlled by electromechanical feedback to increase the pressure when the stimulus is performed.
The electromechanical algometer presented in [6] , called multimodal automated sensory testing (MAST) system, is controlled by signals over a Bluetooth link.
The subjects indicated the pain sensation using a rating scale over a touch screen on a separate computer.
This algometer is portable and composed of a DC servo motor, hand-held thumbnail pressure stimulators, the Bluetooth control system, and a load cell-type force sensor that works by resistive measurement (for measuring the pressure applied).
The so-called Automatic Tissue Tester (ATT) electromechanical algometer was used to apply the pressure stimulus in [7] , the subjects had to stand on a platform, and then the pressure stimulus was applied from the bottom up; therefore, the body parts that were affected were at the bottom of the foot. The electromechanical algometer comprises an indentation speed control, maximum force application of 1500 kPa, a maximum indentation of 35 mm, tension-compression load cell, and a 200 step/revolution stepper motor. In [9] , an electromechanical algometer similar to the one described in [7] was built.
Finally, in [8] [24] , a Biaxial Algometer was used, designed with a pressure application device, a visual analog scale, a user interface, a controller, and an in-line attached load cell force sensor. The algometer can move linearly and rotationally.

Analysis of PPT of the trapezius muscle area
The analysis of pain pressure applied to the trapezius muscle area in healthy participants is presented in Table 2 [15] [19] [21] . One study did not specify the condition of the subjects [17] ; in 5 works, participants with some disease or pain were studied. The disease and pain conditions that affect the subjects are fibromyalgia [15] , low back pain [15] , neck pain [20] , tension-type headache [2] [10] , and pain in the upper trapezius (UT) muscle [11] .
The highest mean value of PPT (512 kPa) was obtained in a test performed on healthy participants with a commercial algometer (Wagner Force Ten) in the upper trapezius muscle [15] . However, the lowest value (110 kPa) [11] has been recorded using the same manual algometer and in the same body part (upper trapezius muscle) on participants with local pain.
In two reports [2] [10] , patients that suffered tension-type headache (TTH) were involved in the study.
The PPT values obtained from these studies were registered using Wagner Instruments algometers [2] and Somedic AB [10] . Together with the previously cited one (110 kPa), these values were the lowest among those measured in the trapezius muscle area.
In [2] , a more in-depth analysis had been performed to  Table 2).  Instead, in [10] , the pressure stimuli were applied while the patients presented a headache, obtaining even lower values (187 kPa on UT right and 186kPa on UT left) for the ones reported in [2] . From these studies, it comes out that the intensity of pain directly affects the pain threshold, the more intense the pain, the lower the threshold. There are no articles that report the use of an electromechanical algometer on the UT.

Analysis of PPT of the back muscle area
In this section, all the studies that applied a pressure stimulus on the back muscle area are considered, and the extracted data are collected in Table 3. All these studies involved healthy participants. Two of them also performed tests on subjects who had fibromyalgia [15] , back pain [15] , and sacroiliac joint pain [13] .
The lowest PPT value was obtained in patients with pain in the sacroiliac joint region (235 kPa), whereas healthy subjects reached the highest values (833 kPa) [13] . Both values were obtained with a manual algometer (Wagner Force Dial TM FDK 40) that was applied to the sacroiliac joint region.
Out of the studies conducted on the back muscle area, an electromechanical algometer is used only in [9] (called computerized deformation-controlled indentation system). Therefore, tests were carried out on the lower back of healthy participants, both with a commercial Wagner FDN 100 algometer (695 kPa) and the electromechanical one (484 kPa). Since both devices    A value of 716 kPa obtained during the investigation in [15] on another patient using a manual Wagner algometer, further confirmed that the mechanical system was probably wrong. This value is 232 kPa above the PPT value reported by the electromechanical algometer in [9] but shows a difference of only 21 kPa for the manual algometer result for the same research [9] .

Analysis of PPT of the upper limbs
In this section, PPT values obtained in upper limbs are collected and reported in Table 4. Among all the studies considered, only five involved healthy subjects [ .    In [6] , only female subjects are considered, while both males and females were included in the others. It should be noted that in [15] , the pressure stimulus was applied between the thumb and the index finger on the dorsal part of the hand, while in the other articles, the pressure was applied on the biceps brachii muscle [16] , thumb [5] [6] , the second metacarpal [2] , and the middle finger [18] . In [5] , tests were performed on the thumb, using a manual algometer (Algometer Type II, Somedic Production AB) and an electromechanical one, obtaining very similar PPT values, 357 kPa, and 371 kPa, respectively.
The PPT values of the second metacarpal, obtained from [2] , were among the lowest ones (268 kPa and 241 kPa); it is worth mentioning that the patients presented TTH. On the other hand, the highest value (897 kPa) was obtained on the middle finger in [18], using a manual algometer (Wagner Force One FDIX 50). It is observed that the PPT value of the middle finger is higher than PPTs extracted from the hand [2] [15] and even higher than those presented on the brachii muscle [16] , giving the impression that a more significant muscle gives higher values. These values can be related to the fact that the nerves responsible for perceiving the fingers' painful stimulus are more distant from the brain than those present in the arm.
The study reported in [6]

Analysis of PPT of the foot area
In the articles presented in Table 6, related to the foot area's pain pressure, both males and females were included, except for [7] , where the participants were only five males. This article is also the only one found in the studied records that applied a pressure stimulus on the foot area with an electromechanical algometer.
In [22] , an analysis of different studies was carried out, The study described in [7] recorded the highest PPT values with respect not only to the foot area but concerning all the papers here considered (see Tables 2-7).
In addition, they recorded three different values on healthy people-1014 kPa, 1039 kPa, and 1074 kPa, on the heel pad with the ATT algometer aforementioned.     Table 7 reports the results obtained from 2 articles [2] [10] that considered the head muscle area. These two studies were already analyzed in section 3.2, related to the trapezius muscle area, where the involved subjects' conditions were deeply detailed.

Analysis of PPT of the head muscles
For the part of the study performed on the head muscles, in [10] , the number of males and females that participated was not specified for both of these studies; pressure stimulations were performed in two placessuboccipital muscles and temporalis muscle, obtaining PPT values in a range from 151 to 212 kPa.

Design characteristic for a functional electromechanical pressure algometer (EPA)
Thanks to the analysis carried out in this work, it is possible to guideline an electromechanical algometer's characteristics. It was concluded that an ideal algometer should be able to measure the PPT in different parts of the body.
An ideal algometer must be designed to be applied to the trapezius muscles, back muscles, upper and lower extremities, and the head area because those areas are the most studied. Table 8 presents an overview of the design features included in the available literature.
A functional algometer should be able to monitor the actual pressure of contact between the algometer and the patient's skin; as well as, the speed rate with which the stimulus is applied, and the penetration distance of the tip into the skin of the subject in order to obtain a more significant amount of standardized data [24] . It would then make it possible to avoid the error produced by the operator of a manual algometer.
Furthermore, error reduction in conjunction with the signals extracted from other devices (such as electroencephalograms, electrocardiograms, skin conductivity sensors, pulse oximeters) could be significantly helpful in future works related to measure physical pain [23] [25] [26] .
Based on the results obtained and the findings of the review performed in this paper, the following characteristics are proposed for the design of an electromechanical pressure algometer:

Physical features
Physical features were proposed based on the common characteristics present in the literature; in particular, the actuator for exerting the movement was a motor because its control is relatively easy to implement; however, an encoder is needed for calculating the motor's velocity and position.

Operating parameters
The following operating parameters are proposed to fulfill all the operating parameters present in the algometers available in the literature. The higher limit for pressure range was proposed based on [7] ; while, the stimulation area was selected to make comparisons with the available algometers easier. From the analysis of all the data collected, the PPT values obtained from people who suffer any form of pain are lower than those obtained in the same body region for healthy people. Therefore, it seems that fibromyalgia has the highest effects in lowering the pain thresholds. The lowest value found among all the considered studies is 98 kPa which was obtained from the dominant thumb [6] on fibromyalgia patients.
Further confirmation comes from [15] where healthy subjects, subjects with low back pain, and patients with fibromyalgia were considered for the same test.
During this investigation, it was noticed that subjects with fibromyalgia had the lowest PPT values among the three groups that were registered.
It can also be observed that a headache strongly affects the perception of pain. Several of the lowest values of PPTs were obtained while the subjects had a headache.
So, the results showed 186 kPa, and 187 kPa values on the UT region [10] , while it showed values of 215 kPa and 222 kPa on the C5/C6 zygapophyseal joint [2] .
Another result from studies performed on patients with headaches [2] [10] is that pain intensity directly affects the pain threshold-the more intense the pain, the lower the threshold.   Only in one work [9] the mean values of PPTs, which were obtained with an electromechanical device, presented discrepancies related to the PPT values compared with the manual ones. This discrepancy is probably related to the indentation speed [9] .
It is essential to emphasize that the values obtained from healthy people [6] are notably lower than those obtained from the same body part of those in [5] . This difference may have been caused by the fact that in [6] , only female subjects were under experimentation. These lower values agree with the results and conclusions reported in several other works [13] [17] [19] [21] [27] , where PPT values evaluated on females were significantly lower than the corresponding PPTs on male subjects. Table 9 summarizes the lowest and the highest PPT values among all these articles concerning the six different body parts. The lowest value (98 kPa) obtained in [6] was registered on patients with fibromyalgia, applying a pressure stimulus with the dominant thumb's MAST algometer. Whereas the heel pad region is the least sensitive area of the human body since all the studies presented in Tables 2-7 showed high PPT values. It was concluded that the heel pad is the body site where the highest pain thresholds are held, ranging from 1014 kPa to 1074 kPa. These PPT values were obtained using the ATT algometer on healthy subjects [7] . As it can be noticed, these extreme values have been measured with electromechanical algometers.
The measurements of several PPT values were collected and critically compared for different body areas.
These values verified that healthy subjects have higher PPTs than those who present some disease or pain.
Moreover, we have found evidence that the intensity of pain directly affects the pain threshold; demonstrating that as the pain level increases, the subject's pain threshold decreases regardless the type of pain.
From these values, a database of PPTs from different parts of the body is generated. This database could serve as a benchmark for future research with pressure algometers. In addition, in conjunction with other physiological and biometric signals, it could be significantly helpful in future work related to the measurement of pain.
Finally, a guideline for the characteristics that an ideal electromechanical algometer should have is provided. A portable design that measures the PPTs in different body parts and that it is also smaller, lighter, and cheaper than the existing ones is desirable.
The validity and reliability of potential new algometers-either manual or electromechanical, can be evaluated considering the PPT values collected in this paper.

AUTHOR CONTRIBUTIONS
All authors contributed equally to the work.

ETHICAL STATEMENT
This work does not contain any studies with human participants performed by any of the authors.