Advertisement

Central Hypersensitivity in Patients With Subacromial Impingement Syndrome

  • Tracy Maria Paul
    Affiliations
    Case Western Reserve University School of Medicine, Cleveland, OH
    Search for articles by this author
  • Jennifer Soo Hoo
    Affiliations
    Case Western Reserve University School of Medicine, Cleveland, OH
    Search for articles by this author
  • John Chae
    Affiliations
    Department of Physical Medicine and Rehabilitation, Case Western Reserve University at MetroHealth Medical Center, Cleveland, OH

    Cleveland Functional Electrical Stimulation Center, Case Western Reserve University, Cleveland, OH

    Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH
    Search for articles by this author
  • Richard D. Wilson
    Correspondence
    Correspondence to Richard D. Wilson, MD, Dept of Physical Medicine and Rehabilitation, Case Western Reserve University at MetroHealth Medical Center, 2500 MetroHealth Dr, R-230, Cleveland, OH 44109
    Affiliations
    Department of Physical Medicine and Rehabilitation, Case Western Reserve University at MetroHealth Medical Center, Cleveland, OH

    Cleveland Functional Electrical Stimulation Center, Case Western Reserve University, Cleveland, OH
    Search for articles by this author

      Abstract

      Paul TM, Soo Hoo J, Chae J, Wilson RD. Central hypersensitivity in patients with subacromial impingement syndrome.

      Objective

      To investigate the presence of primary and secondary hyperalgesia among subjects with chronic subacromial impingement syndrome (SIS) compared with pain-free controls.

      Design

      Cross-sectional design.

      Setting

      Outpatient rehabilitation clinic, urban, academic medical center.

      Participants

      Volunteer sample (N=62) (31 with SIS, 31 controls).

      Interventions

      Not applicable.

      Main Outcome Measures

      Pressure-pain thresholds (PPTs) were measured at the middle deltoid of the affected/dominant arm (primary or secondary hyperalgesia) and the middle deltoid and tibialis anterior of the unaffected/nondominant side (secondary hyperalgesia) in SIS and healthy controls, respectively. Differences in PPTs were analyzed by Wilcoxon rank sum test and with linear regression analysis controlling for sex, a known confounder of PPTs.

      Results

      After adjusting for sex, subjects with SIS had significantly lower PPTs than did controls at all locations. Controls had a 1.4kg/cm2 (95% confidence interval [CI], 1.2–1.5) higher PPT at their affected shoulder than did those with SIS, a 0.7kg/cm2 (95% CI, 0.5–0.9) higher PPT at their nonaffected shoulder, and a 1.1kg/cm2 (95% CI, 1.1–1.2) higher PPT at their contralateral tibialis anterior. Observers were not blinded to patient groupings but were blinded to the level of applied pressure.

      Conclusions

      This study provides further evidence that patients with SIS have significantly lower PPTs than do controls in both local and distal areas from their affected arm consistent with primary and secondary hyperalgesia, respectively. Data suggest the presence of central sensitization among subjects with chronic SIS.

      Key Words

      List of Abbreviations:

      CI (confidence interval), PPT (pressure-pain threshold), SIS (subacromial impingement syndrome)
      SUBACROMIAL IMPINGEMENT syndrome (SIS) is a common cause of shoulder pain, estimated to be the cause for up to half of incident cases.
      • van der Windt D.A.W.M.
      • Koes B.W.
      • de Jong B.A.
      • Bouter L.M.
      Shoulder disorders in general practice: incidence, patient characteristics, and management.
      Anatomically, SIS refers to the supraspinatus tendon impinging on the undersurface of the anterior acromion as the arm is raised overhead.
      • Neer II, C.S.
      Anterior acromioplasty for the chronic impingement syndrome in the shoulder: a preliminary report.
      Typically, pain is generated with elevation of the arm above the head though it can occur with rest.
      • Neer II, C.S.
      Impingement lesions.
      Many pathologies are found in those with SIS, either alone or conjointly, and include subacromial bursitis, rotator cuff tendinopathy, and partial rotator cuff tears.
      • Bigliani L.U.
      • Levine W.N.
      Subacromial impingement syndrome.
      Treatment generally consists of conservative therapy, though as the duration of shoulder pain from SIS increases, the likelihood of successful treatment becomes worse.
      • Kuijpers T.
      • van der Windt D.A.W.M.
      • Boeke A.J.P.
      • et al.
      Clinical prediction rules for the prognosis of shoulder pain in general practice.
      Up to 45% of those who present to their primary physicians with shoulder pain will either continue to have pain at 2 years or will have gone on to surgical treatment.
      • Cummins C.A.
      • Sasso L.M.
      • Nicholson D.
      Impingement syndrome: temporal outcomes of non-operative treatment.
      Unfortunately, randomized controlled trials have not shown the benefit of surgical treatment over conservative treatment,
      • Dorrestijn O.
      • Stevens M.
      • Winters J.C.
      • van der Meer K.
      • Diercks R.L.
      Conservative or surgical treatment for subacromial impingement syndrome? A systematic review.
      • Ketola S.
      • Lehtinen J.
      • Arnala I.
      • et al.
      Does arthroscopic acromioplasty provide any additional value in the treatment of shoulder impingement syndrome? A two-year randomised controlled trial.
      leaving a large number of those with shoulder pain to suffer from chronic pain. There is now evidence that alterations in the central and peripheral nervous systems may play a role in chronic pain,
      • Petersen-Felix S.
      • Curatolo M.
      Neuroplasticity – an important factor in acute and chronic pain.
      • Curatolo M.
      • Arendt-Nielsen L.
      • Petersen-Felix S.
      Central hypersensitivity in chronic pain: mechanisms and clinical implications.
      • Latremoliere A.
      • Woolf C.J.
      Central sensitization: a generator of pain hypersensitivity by central neural plasticity.
      and may explain why some patients fail to improve in spite of treatment and lack of evidence for persistent pathology.
      There is evidence of secondary hyperalgesia in those who experience chronic shoulder pain from SIS, providing indirect evidence of central hypersensitivity.
      • Hidalgo-Lozano A.
      • Fernández-de-las-Peñas C.
      • Alonso-Blanco C.
      • Ge H.Y.
      • Arendt-Nielsen L.
      • Arroyo-Morales M.
      Muscle trigger points and pressure pain hyperalgesia in the shoulder muscles in patients with unilateral shoulder impingement: a blinded, controlled study.
      Central hypersensitivity is an augmentation of the nociceptive pathways of the central nervous system
      • Petersen-Felix S.
      • Curatolo M.
      Neuroplasticity – an important factor in acute and chronic pain.
      • Curatolo M.
      • Arendt-Nielsen L.
      • Petersen-Felix S.
      Central hypersensitivity in chronic pain: mechanisms and clinical implications.
      • Latremoliere A.
      • Woolf C.J.
      Central sensitization: a generator of pain hypersensitivity by central neural plasticity.
      that is characterized by local and generalized lowered pain thresholds and an exaggerated pain response to painful and nonpainful stimulation. Central hypersensitivity is a normal response of the central nervous system to injury that encourages protection of injured tissue to allow healing.
      • Greene C.S.
      Neuroplasticity and sensitization.
      After the injured tissue has healed, the hypersensitivity to pain typically resolves; however, the central hypersensitivity may persist in some individuals, resulting in a chronic pain syndrome. In the case of those with SIS, central hypersensitivity may be associated with persistent pain in spite of treatment.
      Local and generalized hyperalgesia was demonstrated by Hidalgo-Lozano et al
      • Hidalgo-Lozano A.
      • Fernández-de-las-Peñas C.
      • Alonso-Blanco C.
      • Ge H.Y.
      • Arendt-Nielsen L.
      • Arroyo-Morales M.
      Muscle trigger points and pressure pain hyperalgesia in the shoulder muscles in patients with unilateral shoulder impingement: a blinded, controlled study.
      in the form of lower pain thresholds (ie, pain being perceived at lower mechanical pressure intensities) in the deltoid (local) and ipsilateral tibialis anterior (distal, healthy tissue) compared with control subjects. Hyperalgesia in the shoulder of those with SIS compared with controls could represent either primary or secondary hyperalgesia, which are indirect evidence of peripheral and central hypersensitivity, respectively. Hyperalgesia in distal, healthy tissues in those with SIS compared with controls is evidence of central hyperalgesia because a lower pain threshold in uninvolved tissue would require alterations in the central nervous system.
      • Curatolo M.
      • Arendt-Nielsen L.
      • Petersen-Felix S.
      Central hypersensitivity in chronic pain: mechanisms and clinical implications.
      As noted by the authors, a major limitation of the study was a small sample size. Other limitations in this study include lack of adjusting for sex, age, and ethnicity, all of which have been shown to independently influence pain thresholds,
      • Chesterton L.S.
      • Barlas P.
      • Foster N.E.
      • Baxter G.D.
      • Wright C.C.
      Gender differences in pressure pain threshold in healthy humans.
      • Lautenbacher S.
      • Kunz M.
      • Strate P.
      • Nielsen J.
      • Arendt-Nielsen L.
      Age effects on pain thresholds, temporal summation and spatial summation of heat and pressure pain.
      • Edwards R.R.
      • Doleys D.M.
      • Fillingim R.B.
      • Lowery D.
      Ethnic differences in pain tolerance: clinical implications in a chronic pain population.
      • Mechlin B.M.
      • Maixner W.
      • Light K.C.
      • Fisher J.M.
      • Girdler S.S.
      African Americans show alterations in endogenous pain regulatory mechanisms and reduced pain tolerance to experimental pain procedures.
      lack of evaluating pain thresholds contralateral to the affected side, and not clearly excluding all subjects with other chronic pain syndromes. The objective of this study was to address these limitations and to confirm the presence of primary and secondary hyperalgesia among subjects with chronic shoulder pain due to SIS compared with a pain-free population.

      Methods

      Subjects

      This cross-sectional study was approved by the institutional review board of the authors' local institution. Subjects were recruited from an outpatient rehabilitation clinic including physician and allied health services of an urban, academic medical center. After obtaining informed consent and establishing eligibility, baseline information was collected. Subjects with SIS were 21 years or older, had shoulder pain for at least 6 months, and had shoulder pain of 4 or greater in the last week on a scale of 0 to 10. Subjects with SIS were excluded if they had evidence of joint or overlying skin infection, prior surgery to the affected limb, or had any other chronic pain syndrome. Controls were 21 years or older, were without pain in the prior week greater than 3 on a scale of 0 to 10, and had no pain in a single location for more than 16 days of the last 30. Subjects were also excluded if they had evidence of joint or overlying skin infection or had difficulty understanding instructions related to the determination of a pain threshold.

      Pressure-Pain Threshold

      Hyperalgesia is evaluated by measuring pressure-pain thresholds (PPTs), the minimum amount of pressure at which pain is perceived.
      • Vanderweeën L.
      • Oostendorp R.A.
      • Vaes P.
      • Duquet W.
      Pressure algometry in manual therapy.
      The reliability of pressure algometry to evaluate deep somatic tissue sensitivity has been demonstrated previously.
      • Nussbaum E.L.
      • Downes L.
      Reliability of clinical pressure-pain algometric measurements obtained on consecutive days.
      • Pontinen P.J.
      Reliability, validity, reproducibility of algometry in diagnosis of active and latent tender spots and trigger points.
      • Chesterton L.S.
      • Sim J.
      • Wright C.C.
      • Foster N.E.
      Interrater reliability of algometry in measuring pressure pain thresholds in healthy humans, using multiple raters.
      To discriminate between peripheral and central sensitization, sites of healthy tissue distal to the site of injury were included. Secondary hyperalgesia, a reduction in pain thresholds in healthy tissue distal to the site of injury in those with SIS compared with controls, is indicative that a central process is responsible.
      • Curatolo M.
      • Arendt-Nielsen L.
      • Petersen-Felix S.
      Central hypersensitivity in chronic pain: mechanisms and clinical implications.
      Two assessors obtained PPT measurements in subjects with SIS and controls. The assessors underwent training prior to the study to standardize measurement methods including subject positioning, assessor blinding to pressure reading, and rate of pressure application. PPTs were measured using a hand-held digital algometera with a .785-cm
      • Neer II, C.S.
      Anterior acromioplasty for the chronic impingement syndrome in the shoulder: a preliminary report.
      rubber tip by applying the probe perpendicularly to the skin at a rate of 1 kg/cm2 per second while subjects were seated comfortably with their arms at their sides. The mean of 3 trials at each location was calculated and used for analysis. The PPTs were measured at the middle deltoid of the affected/dominant arm, the unaffected/nondominant arm, and the tibialis anterior on the same side of the body as the unaffected/nondominant arm in those with SIS and controls, respectively. The measurements were obtained in the same order on all subjects.

      Statistical analysis

      Differences in demographic variables between the 2 groups were analyzed with a chi-square test, or Fisher's exact tests for small cell size (<5) for categorical variables and with the Wilcoxon rank sum test for continuous variables. The effect sizes of PPTs between SIS and controls were calculated by the differences of the predicted PPTs from linear regression models with the covariates of sex and age, both known to influence PPTs.
      • Chesterton L.S.
      • Barlas P.
      • Foster N.E.
      • Baxter G.D.
      • Wright C.C.
      Gender differences in pressure pain threshold in healthy humans.
      • Lautenbacher S.
      • Kunz M.
      • Strate P.
      • Nielsen J.
      • Arendt-Nielsen L.
      Age effects on pain thresholds, temporal summation and spatial summation of heat and pressure pain.
      The covariate ethnicity
      • Edwards R.R.
      • Doleys D.M.
      • Fillingim R.B.
      • Lowery D.
      Ethnic differences in pain tolerance: clinical implications in a chronic pain population.
      • Mechlin B.M.
      • Maixner W.
      • Light K.C.
      • Fisher J.M.
      • Girdler S.S.
      African Americans show alterations in endogenous pain regulatory mechanisms and reduced pain tolerance to experimental pain procedures.
      was also evaluated in the prediction models because of its association with PPTs, though it could not be included in the models because of insufficient distribution across groups. Confidence intervals (CIs) were calculated by repeating the regression analysis on boot-strapped samples (with replacement, 1000 iterations) and finding the 2.5 and 97.5 percentiles of the estimates. Because of nonnormal distributions of the PPTs, we transformed the measurements in the primary and subgroup analyses, respectively, of the local deltoid (fourth root, square root), nonaffected deltoid (square root, square root), and tibialis anterior (square root, no transformation) prior to the regression analyses. The predicted values were backtransformed to the original scale before the calculation of PPT differences.

      Hypothesis

      We hypothesized that subjects with SIS will have significantly lower pain thresholds local to and distal from their painful shoulders than healthy control subjects.

      Results

      A total of 64 subjects were enrolled in this study, of which 2 were excluded for difficulty understanding instructions related to the measurement of PPTs. There were 31 cases and 31 controls in the analysis. There were significant differences between groups, with those with SIS being older and having a larger minority representation, as can be seen in table 1.
      Table 1Demographic Information
      VariableSIS PatientsControlsP
      n3131
      Females, n (%)16 (51.6)21 (67.7)0.2
      Age (y), mean ± SD51.7±10.039.5±10.90.02
      Ethnicity
       White, n (%)16 (51.6)29 (93.6)0.001
       African American, n (%)12 (38.7)1 (3.2)0.001
       Other, n (%)3 (9.7)1 (3.2)0.6
      The mean PPTs for SIS and controls at their affected/dominant shoulder and contralateral shoulder and tibialis anterior are shown in figure 1. We used linear regression models to predict the effect size of the differences in PPTs for subjects with SIS compared with controls when taking into account sex and age differences. The models revealed significantly lower PPTs for subjects with SIS at all locations tested. The estimated effect sizes for PPTs for those with SIS were lower than those for controls at their affected shoulder by 1.7kg/cm2 (95% CI, 1.5–2.0), lower by 0.9kg/cm2 (95% CI, 0.6-1.1) at their nonaffected shoulder, and lower by 1.5kg/cm2 (95% CI, 1.4–1.5) at their contralateral tibialis anterior.
      Figure thumbnail gr1
      Fig 1Pressure-pain thresholds (kg/cm2) of subjects with SIS (n=31) and pain-free controls (n=31). The errors bars indicate standard error.
      To control for potential differences in race that we could not adjust for in our models, the analyses were repeated on whites because they represented 73.4% of the sample. The estimated effect sizes for PPTs for those with SIS were lower than those for controls at their affected shoulder by 1.3kg/cm2 (95% CI, 0.9–1.47), lower by 0.8kg/cm2 (95% CI, 0.4–1.1) at their nonaffected shoulder, and lower by 1.8kg/cm2 (95% CI, 0.8–1.1) at their contralateral tibialis anterior.

      Discussion

      The current results are in agreement with prior work that demonstrated lower PPTs in local and ipsilateral distal locations in patients with chronic SIS, consistent with primary and secondary hyperalgesia, respectively.
      • Hidalgo-Lozano A.
      • Fernández-de-las-Peñas C.
      • Alonso-Blanco C.
      • Ge H.Y.
      • Arendt-Nielsen L.
      • Arroyo-Morales M.
      Muscle trigger points and pressure pain hyperalgesia in the shoulder muscles in patients with unilateral shoulder impingement: a blinded, controlled study.
      Our study provides greater evidence for widespread central hypersensitivity through lower PPTs on the contralateral shoulder and contralateral tibialis anterior in addition to the affected shoulder in SIS subjects compared with control subjects. We also improved on the prior study by recruiting a larger sample (62 subjects compared with 22) by excluding all subjects with a chronic pain syndrome other than SIS, and by adjusting for the effect of sex in our analyses.
      Reduced pain thresholds at healthy tissues distal to the affected shoulder provide further support for the presence of widespread central hypersensitivity for those with chronic SIS. Lower pain thresholds compared with normal values in pain-free control subjects have been suggested as a clinically meaningful difference.
      • Fischer A.A.
      Pressure threshold meter: its use for quantification of tender spots.
      Persistence of central hypersensitivity has been suggested in multiple chronic pain conditions, demonstrated by reduced pain thresholds in healthy tissues distal to the site of injury when compared with healthy control subjects.
      • Latremoliere A.
      • Woolf C.J.
      Central sensitization: a generator of pain hypersensitivity by central neural plasticity.
      • Hidalgo-Lozano A.
      • Fernández-de-las-Peñas C.
      • Alonso-Blanco C.
      • Ge H.Y.
      • Arendt-Nielsen L.
      • Arroyo-Morales M.
      Muscle trigger points and pressure pain hyperalgesia in the shoulder muscles in patients with unilateral shoulder impingement: a blinded, controlled study.
      • Scott D.
      • Jull G.
      • Sterling M.
      Widespread sensory hypersensitivity is a feature of chronic whiplash-associated disorder but not chronic idiopathic neck pain.
      • Desmeules J.A.
      • Cedraschi C.
      • Rapiti E.
      • et al.
      Neurophysiologic evidence for a central sensitization in patients with fibromyalgia.
      • Fernández-de-las-Peñas C.
      • de la Llave-Rincón A.I.
      • Fernández-Carnero J.
      • et al.
      Bilateral widespread mechanical pain sensitivity in carpal tunnel syndrome: evidence of central processing in unilateral neuropathy.
      • Bendtsen L.
      • Jensen R.
      • Olesen J.
      Decreased pain detection and tolerance thresholds in chronic tension-type headache.
      • Svensson P.
      • List T.
      • Hector G.
      Analysis of stimulus-evoked pain in patients with myofascial temporomandibular pain disorders.
      The association of chronic pain and central hypersensitivity is not well understood, though there is evidence that persistent central hypersensitivity is a consequence of chronic pain rather than a risk factor for chronic pain.
      • Buchgreitz L.
      • Lyngberg A.C.
      • Bendtsen L.
      • Jensen R.
      Increased pain sensitivity is not a risk factor but a consequence of frequent headache: a population-based follow-up study.
      This finding raises the possibility that successfully treating chronic SIS may need to address more than biomechanical or anatomic pathologies alone.

      Study Limitations

      There are limitations to our study that should be kept in mind. We were unable to limit analgesic usage among the subjects with SIS. However, medication use would be expected to raise the PPTs for those with SIS and bias against a difference between the PPTs of subjects with SIS and controls. Differences in estimated PPTs were found despite this limitation, though it may cause underestimation of the true difference in PPTs between those with chronic pain and without. Second, our sample was not a random sample; thus, the true difference in PPTs in those with chronic SIS and without may be different than that seen in this study. Third, the evaluators were not blinded to case and control subjects and could have potentially introduced bias into the study; however, efforts were made to reduce bias by blinding evaluators to PPT levels during testing. Finally, there were significant differences in sex, age, and ethnicity that could contribute to differences between those with SIS and controls. While we adjusted for sex and age, we could not adjust for race within the models because of the lack of distributional overlap between the groups. Race has been shown to be significantly associated with pain perception,
      • Edwards R.R.
      • Doleys D.M.
      • Fillingim R.B.
      • Lowery D.
      Ethnic differences in pain tolerance: clinical implications in a chronic pain population.
      • Mechlin B.M.
      • Maixner W.
      • Light K.C.
      • Fisher J.M.
      • Girdler S.S.
      African Americans show alterations in endogenous pain regulatory mechanisms and reduced pain tolerance to experimental pain procedures.
      with minorities having lower pain thresholds than whites, and this could bias toward the differences observed in this study. We repeated the analyses in whites only and while the magnitude of difference is lower, widespread hyperalgesia is observed in those subjects with SIS compared with pain-free controls and thus the conclusions of our study are unchanged.

      Conclusions

      This study provides further evidence that subjects with chronic shoulder pain due to SIS have lower pain thresholds than do control subjects in both local areas and distal areas from their affected arm. This suggests that subjects with SIS may be experiencing central hypersensitivity. Further studies of the relationship of PPTs and chronic pain syndromes should be conducted including longitudinal studies of central hypersensitivity in subjects with chronic shoulder pain undergoing treatment, which would improve our understanding of this association.
      • a
        Wagner Pain Test – Model FPIX Digital Algometer; Wagner Instruments, PO Box 1217, Greenwich, CT 06836.

      Acknowledgment

      We thank Steven M. Sidik, PhD, of the Cleveland FES Center (staff statistician) and Department of Statistics, Case Western Reserve University (lecturer), for assistance in statistical analyses.

      References

        • van der Windt D.A.W.M.
        • Koes B.W.
        • de Jong B.A.
        • Bouter L.M.
        Shoulder disorders in general practice: incidence, patient characteristics, and management.
        Ann Rheum Dis. 1995; 54: 959-964
        • Neer II, C.S.
        Anterior acromioplasty for the chronic impingement syndrome in the shoulder: a preliminary report.
        J Bone Joint Surg Am. 1972; 54: 41-50
        • Neer II, C.S.
        Impingement lesions.
        Clin Orthop Relat Res. 1983; : 70-77
        • Bigliani L.U.
        • Levine W.N.
        Subacromial impingement syndrome.
        J Bone Joint Surg Am. 1997; 79: 1854-1868
        • Kuijpers T.
        • van der Windt D.A.W.M.
        • Boeke A.J.P.
        • et al.
        Clinical prediction rules for the prognosis of shoulder pain in general practice.
        Pain. 2006; 120: 276-285
        • Cummins C.A.
        • Sasso L.M.
        • Nicholson D.
        Impingement syndrome: temporal outcomes of non-operative treatment.
        J Shoulder Elbow Surg. 2009; 18: 172-177
        • Dorrestijn O.
        • Stevens M.
        • Winters J.C.
        • van der Meer K.
        • Diercks R.L.
        Conservative or surgical treatment for subacromial impingement syndrome?.
        J Shoulder Elbow Surg. 2009; 18: 652-660
        • Ketola S.
        • Lehtinen J.
        • Arnala I.
        • et al.
        Does arthroscopic acromioplasty provide any additional value in the treatment of shoulder impingement syndrome?.
        J Bone Joint Surg Br. 2009; 91: 1326-1334
        • Petersen-Felix S.
        • Curatolo M.
        Neuroplasticity – an important factor in acute and chronic pain.
        Swiss Med Wkly. 2002; 132: 273-278
        • Curatolo M.
        • Arendt-Nielsen L.
        • Petersen-Felix S.
        Central hypersensitivity in chronic pain: mechanisms and clinical implications.
        Phys Med Rehabil Clin North Am. 2006; 17: 287-302
        • Latremoliere A.
        • Woolf C.J.
        Central sensitization: a generator of pain hypersensitivity by central neural plasticity.
        J Pain. 2009; 10: 895-926
        • Hidalgo-Lozano A.
        • Fernández-de-las-Peñas C.
        • Alonso-Blanco C.
        • Ge H.Y.
        • Arendt-Nielsen L.
        • Arroyo-Morales M.
        Muscle trigger points and pressure pain hyperalgesia in the shoulder muscles in patients with unilateral shoulder impingement: a blinded, controlled study.
        Exp Brain Res. 2010; 202: 915-925
        • Greene C.S.
        Neuroplasticity and sensitization.
        JADA. 2009; 140: 676-678
        • Chesterton L.S.
        • Barlas P.
        • Foster N.E.
        • Baxter G.D.
        • Wright C.C.
        Gender differences in pressure pain threshold in healthy humans.
        Pain. 2003; 101: 259-266
        • Lautenbacher S.
        • Kunz M.
        • Strate P.
        • Nielsen J.
        • Arendt-Nielsen L.
        Age effects on pain thresholds, temporal summation and spatial summation of heat and pressure pain.
        Pain. 2005; 115: 410-418
        • Edwards R.R.
        • Doleys D.M.
        • Fillingim R.B.
        • Lowery D.
        Ethnic differences in pain tolerance: clinical implications in a chronic pain population.
        Psychosom Med. 2001; 63: 316-323
        • Mechlin B.M.
        • Maixner W.
        • Light K.C.
        • Fisher J.M.
        • Girdler S.S.
        African Americans show alterations in endogenous pain regulatory mechanisms and reduced pain tolerance to experimental pain procedures.
        Psychosom Med. 2005; 67: 948-956
        • Vanderweeën L.
        • Oostendorp R.A.
        • Vaes P.
        • Duquet W.
        Pressure algometry in manual therapy.
        Man Ther. 1996; 1: 258-265
        • Nussbaum E.L.
        • Downes L.
        Reliability of clinical pressure-pain algometric measurements obtained on consecutive days.
        Phys Ther. 1998; 78: 160-169
        • Pontinen P.J.
        Reliability, validity, reproducibility of algometry in diagnosis of active and latent tender spots and trigger points.
        in: Fischer A.A. Muscle pain syndromes and fibromyalgia pressure algometry for quantification of diagnosis and treatment outcome. Haworth Medical Pr, New York1998: 1-158
        • Chesterton L.S.
        • Sim J.
        • Wright C.C.
        • Foster N.E.
        Interrater reliability of algometry in measuring pressure pain thresholds in healthy humans, using multiple raters.
        Clin J Pain. 2007; 23: 760
        • Fischer A.A.
        Pressure threshold meter: its use for quantification of tender spots.
        Arch Phys Med Rehabil. 1986; 67 (836-8)
        • Scott D.
        • Jull G.
        • Sterling M.
        Widespread sensory hypersensitivity is a feature of chronic whiplash-associated disorder but not chronic idiopathic neck pain.
        Clin J Pain. 2005; 21: 175-181
        • Desmeules J.A.
        • Cedraschi C.
        • Rapiti E.
        • et al.
        Neurophysiologic evidence for a central sensitization in patients with fibromyalgia.
        Arthritis Rheum. 2003; 48: 1420-1429
        • Fernández-de-las-Peñas C.
        • de la Llave-Rincón A.I.
        • Fernández-Carnero J.
        • et al.
        Bilateral widespread mechanical pain sensitivity in carpal tunnel syndrome: evidence of central processing in unilateral neuropathy.
        Brain. 2009; 132: 1472-1479
        • Bendtsen L.
        • Jensen R.
        • Olesen J.
        Decreased pain detection and tolerance thresholds in chronic tension-type headache.
        Arch Neurol. 1996; 53: 373-376
        • Svensson P.
        • List T.
        • Hector G.
        Analysis of stimulus-evoked pain in patients with myofascial temporomandibular pain disorders.
        Pain. 2001; 92: 399-409
        • Buchgreitz L.
        • Lyngberg A.C.
        • Bendtsen L.
        • Jensen R.
        Increased pain sensitivity is not a risk factor but a consequence of frequent headache: a population-based follow-up study.
        Pain. 2008; 137: 623-630