Current Concept of Quantitative Sensory Testing and Pressure Pain Threshold in Neck/Shoulder and Low Back Pain

In recent years, several published articles have shown that quantitative sensory testing (QST) and pressure pain threshold (PPT) are useful in the analysis of neck/shoulder and low back pain. A valid reference for normal PPT values might be helpful for the clinical diagnosis of abnormal tenderness or muscle pain. However, there have been no reliable references for PPT values of neck/shoulder and back pain because the data vary depending on the devices used, the measurement units, and the area examined. In this article, we review previously published PPT articles on neck/shoulder and low back pain, discuss the measurement properties of PPT, and summarize the current data on PPT values in patients with chronic pain and healthy volunteers. We also reveal previous issues related to PPT evaluation and discuss the future of PPT assessment for widespread use in general clinics. We outline QST and PPT measurements and what kinds of perceptions can be quantified with the PPT. Ninety-seven articles were selected in the present review, in which we focused on the normative values and abnormal values in volunteers/patients with neck/shoulder and low back pain. We conducted our search of articles using PubMed and Medline, a medical database. We used a combination of “Pressure pain threshold” and “Neck shoulder pain” or “Back pain” as search terms and searched articles from 1 January 2000 to 1 June 2022. From the data extracted, we revealed the PPT values in healthy control subjects and patients with neck/shoulder and low back pain. This database could serve as a benchmark for future research with pressure algometers for the wide use of PPT assessment in clinics.


Introduction
Musculoskeletal disease is a worldwide problem for which healthcare assistance is frequently sought. Low back pain (LBP) and neck/shoulder pain are the most common musculoskeletal conditions that evolve into chronic problems [1,2]. Musculoskeletal pathology may initiate chronic pain, but the pain is often also modulated by sensory inputs from the peripheral and central nervous systems [3]. Central sensitization is involved in the chronification of pain, which manifests as hypersensitivity to pain and is spread beyond the areas immediately affected by musculoskeletal pathology [4]. It continues to be challenging to detect and measure hypersensitivity in clinical practice, and no consensus has been reached on which tools are best for assessing musculoskeletal pain [2].
Quantitative sensory testing (QST) combines simple tools that can assess the ability to perceive touch, vibration, proprioception, and sensitivity to pinpricks or blunt pressure and to cold or heat stimuli [2]. QST and the assessment of the pressure pain threshold (PPT) have become commonplace in clinical neurophysiology units [5][6][7][8]. QST/PPT uses psychophysical tests defined as stimuli with predetermined physical properties based on specific measurement protocols for the analysis of somatosensory aberrations. QST/PPT measures sensory stimuli and can be used to assess somatosensory system functions, the measurement of altered peripheral and/or central pain sensitivity, and descending pain modulation [8].
PPT is the QST parameter most frequently used to investigate local and widespread hyperalgesia. PPT reflects sensitivity to pain and can be measured by either electronic or mechanical pressure algometry. In this test, subjects report when gradually applied pressure changes from a feeling of pressure to that of pressure combined with pain [8]. The advantages of PPT include its simplicity and rapid measurement time compared to other QST protocols in which measurement time is longer and requires more effort [5,9,10].
Several articles published over recent years have shown the usefulness of PPT in analyzing neck/shoulder and back pain [11][12][13][14][15][16][17]. Evidence from these studies indicates that PPT would appear to be a useful tool for analyzing the pathogenesis, classification, differential diagnosis, and prognosis of neck/shoulder and back pain [11]. However, the assessment of neck/shoulder and back pain with PPT has one main problem. Standardized normative values for neck/shoulder and back pain conditions are lacking and need to be developed. Although valid reference values indicative of a normal PPT would aid in the clinical diagnosis of muscle pain or abnormal tenderness, no such reliable values currently exist for neck/shoulder and back pain [17].
Therefore, the aims of the present article are to review previously published articles on PPT for neck/shoulder pain and LBP, to discuss measurement properties of PPT, and to review and summarize the present data on PPT values in patients with chronic neck/shoulder and LBP and healthy volunteers, based on our search of the current knowledge base on PPT. We also reveal previous issues related to the PPT evaluation of patients with chronic pain and discuss the future of PPT for widespread use in general clinics.

Quantitative Sensory Testing
QST collectively refers to a group of procedures that assess the perceptual response to systematically applied and quantitative sensory stimuli to characterize somatosensory function or dysfunction [8,18]. QST involves procedures that test perception, pain threshold, and pain tolerance thresholds for different stimuli based on the application of standardized pressure, vibration, thermal, or electrical impulses. QST measures the response to sensory stimuli and can be used to assess somatosensory system function, the measurement of altered peripheral and/or central pain sensitivity, and descending pain modulation [8,19].
By selecting various QST modalities, different fibers can be tested. The function of Aδ fibers is represented by the cold detection threshold, that of C fibers by the heat detection threshold, that of nociceptive C fibers mainly by the heat pain threshold, and that of Aβ fibers by mechanical detection and vibration [11,18,20]. The thermal, mechanical, and electrical tests commonly applied in QST are listed in Table 1 [20][21][22].

Pressure Pain Threshold
Among the QST parameters, PPT is the most frequently assessed. PPT is determined by applying a mechanical stimulus to determine the moment that the stimulus-induced sensation of pressure first changes to that of pain [23]. This allows the quantification of the PPTs of skin and muscle. An algometer is often used to apply pressure to sites both close and far from the location of the subject's pain. Factors such as sex, the investigator, and the apparatus used may affect the measurement of PPT by pressure algometry. The reliability of PPT based on raters or measurement frequencies is reported to be relatively high [23,24].

Perceptions of Peripheral and Central Sensitization Can Be Quantified by PPT
PPT can be used to evaluate peripheral and central sensitization. Tenderness experienced with blunt pressure may be caused by the peripheral sensitization of primary afferents or central sensitization [25]. Because PPT preferentially activates deep afferents, it is a good clinical device for measuring peripheral sensitization. Hyperalgesia of the affected area to blunt mechanical stimuli is thought to reflect the peripheral sensitization of Aδ and C fibers. Unlike cutaneous nociceptors, which are particularly sensitive to thermal stimuli, nociceptors in deep somatic tissue, such as joints and muscles, exhibit a pronounced sensitivity to mechanical stimuli [25,26].
PPT can also assess central sensitization, which can cause mechanical receptive fields to expand. Although this might account for some local spreading of tenderness, the alteration of pathways descending from the brainstem is more likely to result in widespread or generalized tenderness. A widespread lowering of PPT may reflect the dysfunction of the endogenous pain inhibitory mechanism [25][26][27].

PPT Analysis in Neck/Shoulder and Low Back Pain
PPT is also effective in disorders involving musculoskeletal pain. Pressure stimuli generated by an algometer can target muscles or fascia, thus indicating that the application of such stimuli would be suitable for patients with muscle or joint pain [28]. The reliability of algometer use in patients with musculoskeletal pain has been established. In addition, in a reliability study using several PPTs, algometers were reported to have the least variability and highest reliability in assessing musculoskeletal pain [26,28]. Distinguishing between alterations in peripheral and central pain processing in patients with musculoskeletal pain is important, as central sensitization is considered a potential influence in the development and maintenance of chronic pain. There are many reports on the use of PPT in patients with neck/shoulder, low back, and other musculoskeletal pain [28]. Furthermore, PPT might be valuable in predicting postoperative pain after surgery on musculoskeletal structures [2,6,9]. PPT can be used to evaluate the pathophysiology of peripheral and central sensitization in patients with neck/shoulder and LBP and is useful when analyzing the pathogenesis of chronic pain as well as its classification, differential diagnosis, and prediction [12].
They are meaningful evaluation techniques for patients with chronic pain because it is generally very difficult to objectively score how much pain the patients feel in the neck/shoulder and back area, including central sensitizations. PPT examination is one of the solutions to examining patients with chronic pain for digitalization [12]. However, no reviews of previous articles on PPT analysis for chronic neck/shoulder and LBP have been published, nor have standardized methods of assessing PPT for musculoskeletal pain been reported. Moreover, the results are different in the articles showing standardized, normative, and abnormal PPT values of neck/shoulder and LBP in volunteers/patients with and without chronic pain [12].
For these reasons, PPT is not a popular tool in the evaluation of patients with chronic pain even now in general clinics [11]. It is necessary to review all articles on PPT related to neck/shoulder and LBP in volunteers/patients with and without chronic pain in order to achieve the wide and general use of PPT examination. In addition, issues related to recent PPT analysis from the review of the published articles should be pointed out. In the next section, we discuss the previously published articles on PPT for neck/shoulder and LBP published from 2000 to 2022 (Tables 2 and 3). We also reveal the normative and abnormal values for the neck, shoulder, and back, retrieved from the published articles, because these values would be the most important in helping clinicians to distinguish whether patients have abnormal pain. In addition, these data would be meaningful for clinical use in general clinics to help popularize PPT as an examination tool.

Systematic Review of PPT Values in Healthy Control Subjects and Patients with Neck/Shoulder and Low Back Pain
In this section, we review normal and abnormal PPT values in patients with neck/ shoulder and LBP, PPT devices, and the area of PPT examination from the selected articles.

Methods of Literature Search and Inclusion Criteria
We conducted a systematic review according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines (https://prisma-statement.org/; accessed on 1 June 2022). Using the PubMed/MEDLINE database, we first identified relevant articles using the search terms "Pressure pain threshold" AND "Neck shoulder pain" OR "Back pain" published until 1 June 2022 from 1 January 2000. Based on this review of the article titles, we selected relevant titles related to our review. We excluded articles that were not written in the English language. These titles underwent an abstract review, after which unrelated titles were excluded. Additional relevant publications were identified and added after review of reference lists. The remaining articles underwent a full-text review. Articles without full text were excluded. Animal studies were also excluded.
The criteria for selection of the articles were: (1) PPT values as one of the main outcomes; (2) measurement site and method of assessment of PPT were described in detail; (3) the articles were written in English. For this review on musculoskeletal pain, we focused on neck/shoulder pain and back pain, for which PPT values are frequently reported in musculoskeletal pain.

Study Selection
We identified a total of 6523 articles through our database search. After title review and the removal of duplicates, 6275 articles were excluded, and 248 articles underwent abstract and full-text review. A total of 151 articles were excluded on full-text review. The reasons for the exclusion of studies were: (1) PPT value was not listed as one of the main outcomes; (2) The measurement site and method of assessment of PPT were not described in detail, and the articles were written in English; (3) There were no written in PPT values; (4) They were deemed unsuitable after a discussion. Ninety-seven studies met the criteria for review. The search flow diagram is displayed in Figure 1. Titles and abstracts of the studies identified by the search strategy were independently screened by two reviewers (H.S. and S.T.) to determine potentially relevant studies. Full texts of potentially relevant studies were retrieved and evaluated for eligibility by the same reviewers. Any disagreements were resolved via consensus; if consensus could not be reached, a third, independent reviewer (T.S.) resolved the dispute. As shown in Tables 2 and 3, 97 articles were selected in the present review, in which we focused on the normative values and abnormal values in volunteers/patients with neck/shoulder and LBP based on the values reported in the articles, because it was difficult to compare the effects of each treatment directly. The subjects ranged in age from 18 to 75 years old. The majority of the studies used pressure algometers manufactured by Somedic AB (Sweden) or Wagner Instruments (Greenwich, CT, USA).

Quality Assessment and Risk of Bias Assessment
Two review authors (H.S. and S.T.) independently performed the risk of bias assessment, and a third review author (Y.I.) was involved in case of disagreement. The Cochrane Back Review Group "risk of bias" tool was used. All studies had at least one serious risk of bias, with a consequent overall serious risk of bias for those studies. Critical appraisal revealed a spread in methodological quality. Common areas of bias were the lack of use of accepted diagnostic criteria for neck/shoulder/back pain and the lack of reporting of the validity and reliability of the measurement device. Furthermore, all studies had high selection bias because no study reported randomly selecting or consecutively recruiting participants.

Neck/Shoulder Pain
Forty-nine studies, in which the PPT of the neck-shoulder area was measured in patients with neck/shoulder pain and/or healthy volunteers, are listed in Table 2  . The  Tables 2 and 3, 97 articles were selected in the present review, in which we focused on the normative values and abnormal values in volunteers/patients with neck/shoulder and LBP based on the values reported in the articles, because it was difficult to compare the effects of each treatment directly. The subjects ranged in age from 18 to 75 years old. The majority of the studies used pressure algometers manufactured by Somedic AB (Sweden) or Wagner Instruments (Greenwich, CT, USA).

Quality Assessment and Risk of Bias Assessment
Two review authors (H.S. and S.T.) independently performed the risk of bias assessment, and a third review author (Y.I.) was involved in case of disagreement. The Cochrane Back Review Group "risk of bias" tool was used. All studies had at least one serious risk of bias, with a consequent overall serious risk of bias for those studies. Critical appraisal revealed a spread in methodological quality. Common areas of bias were the lack of use of accepted diagnostic criteria for neck/shoulder/back pain and the lack of reporting of the validity and reliability of the measurement device. Furthermore, all studies had high selection bias because no study reported randomly selecting or consecutively recruiting participants.

Neck/Shoulder Pain
Forty-nine studies, in which the PPT of the neck-shoulder area was measured in patients with neck/shoulder pain and/or healthy volunteers, are listed in Table 2  . The subjects of studies of healthy volunteers, workers, children, and young adults without pain were also reported in 10 articles, shown at the bottom of Table 2 [67][68][69][70][71][72][73][74][75]. These articles revealed the normative values of PPT in the neck-shoulder area. PPT was examined in the areas of the deltoid, trapezius, sternocleidomastoid, supraspinatus, and infraspinatus muscles, spinal processes, and C5-C6 zygapophyseal joints. Several devices and different units of measurement were used in the examination. The most common device used was a pressure algometer from Somedic AB, and the measurement unit was kPa. The normative PPT values obtained from the previous data ranged from 175 to 420 kPa at the neck-shoulder area, indicating variability in the data. In addition, several papers compared the data from healthy controls with those of the patients with chronic pain in the neck or shoulder. Nine articles showed the normative value, while data values in comparative tests ranged from 151 to 337 kPa at this area [33][34][35]40,41,[47][48][49]53,[55][56][57][58][59]65], again revealing variability in the data.
There were 39 studies that measured PPT in the neck-shoulder area of patients with neck/shoulder pain ( Table 2) . Algometers made by Somedic AB (units in kPa) and Wagner Instruments (units in kg/cm 2 ) were mainly used for PPT measurements, but more than 10 different devices were used in the articles. The areas of PPT examination were the deltoid, trapezius, levator scapulae, semispinalis capitis, sternocleidomastoid, supraspinatus, and infraspinatus muscles, spinal processes, suboccipital muscles, and C5-C6 zygapophyseal joints. The trapezius muscle and levator scapulae were the most commonly evaluated areas of PPT [33,34,41,53,[55][56][57]64,66,70,73,74], but the analyzed areas differed widely in the articles. The abnormal values of PPT in the trapezius muscle of the patients with chronic neck or shoulder pain were reported to vary from 151 to 411 kPa and 1.35 to 4.14 kg/cm 2 [33,34,41,53,[55][56][57]64], with varying data depending on the device and units used. From this review of previously published articles evaluating neck-shoulder pain using algometers to measure PPT, we think that it is difficult to show the abnormal and cutoff values of patients/volunteers with chronic neck or shoulder pain because the devices, measurement units, and PPT data vary widely across the different papers. However, a difference score above 25-81 kPa between the patients with neck or shoulder pain and healthy control subjects was a meaningful difference for PPT measured by Somedic AB algometers (Table 2) [33,34,41,53,[55][56][57]64].

Discussion
Previously published articles revealed that the individuals with higher scores in the pain-related questionnaire and with a higher score of central sensitization showed lower values on PPT; in addition, previous studies consistently demonstrated that there was a moderate to strong correlation between PPT value and disability/pain intensity . Although valid reference values indicative of a normal and abnormal PPT would aid in the clinical diagnosis of pain, no such reliable values and no published review articles currently exist for neck/shoulder and back pain [17].
To the best of our knowledge, this is the first review article to summarize and evaluate the previously published articles on PPT in patients with neck/shoulder and LBP and to analyze the existing data on PPT values. In the general population, variations in PPT can be associated with several factors, including ethnicity, sex, age, anxiety, and physical activity [8][9][10][11][12][13][14][15][16][17]. Although data on PPT collected by a number of different researchers and the use of different algometers can also be sources of variation in PPT results, in general, the studies showed the high reliability of pressure algometry [22]. However, the evaluation of PPT in general clinics has not been a popular method for patients with pain, possibly because of the difference in results among the articles showing the normative and abnormal PPT values of neck/shoulder and back pain in volunteers/patients with and without pain [11] (Tables 2 and 3). Despite the many articles dealing with PPT data, no work has synthesized assertive pain threshold values. Therefore, we performed this literature review to better understand the problem of measuring pain sensation.
The PPT values collected from several studies were obtained from varying parts of the body and thus may not be directly comparable [22,[29][30][31][32][33][34][35][36][37][38][39][40]. However, using these values, we propose a database of PPTs that could serve as a benchmark for future research with pressure algometers on healthy subjects and subjects with some disease or pain.
From these values, a database of PPTs in neck/shoulder and back pain can be 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 quite helpful in future work related to the measurement of pain. However, we still have several issues regarding PPT analysis. Each institute used each device and measured in a different way during PPT examination. This is the problem of PPT analysis for standardization. We think that worldwide guidelines are required for the standardization of PPT examination from now.
Finally, another guideline is required that describes the characteristics of an ideal algometer for the measurement of PPT. A portable algometer is needed for the measurement of the PPT of different body parts that is smaller, lighter, and cheaper than current devices. The validity and reliability of newly designed manual or electromechanical algometers can then be evaluated considering the PPT values collected and shown in this paper.

Conclusions
In conclusion, we revealed the normative and abnormal values for neck/shoulder and back pain conditions in PPT analysis from the previously published articles. However, the instruments, methods and areas of PPT examination were not standardized. The differences between each institution and facility remain issues of concern for PPT analysis and standardization.