To assess topographical pressure pain sensitivity maps of the hand in patients with unilateral carpal tunnel syndrome (CTS) as compared with healthy subjects.
To assess topographical pressure pain sensitivity maps of the hand in patients with unilateral carpal tunnel syndrome (CTS) as compared with healthy subjects.
A total of 20 women with CTS (ages 32–52 years) and 20 healthy matched women (ages 32–51 years) were recruited. Pressure pain thresholds (PPTs) were measured bilaterally over 30 locations of the palm of each hand by an assessor blinded to the subjects' conditions.
Patients showed lower PPTs in both hands in all of the measurement points as compared with controls (P < 0.001 for all). PPTs were lower in those points over the proximal phalanx of the fingers and the thenar eminency as compared with those points located over the distal phalanx of the fingers (P < 0.001). CTS patients showed lower PPT levels in dermatomes C6, C7, and C8 when compared with healthy controls (P < 0.001 for all), but without differences between dermatomes (P = 0.4). PPT was negatively correlated with both hand pain intensity and duration of symptoms (P < 0.001 for all).
Our findings revealed bilateral generalized pressure pain hyperalgesia in unilateral CTS because lower PPT levels were found in all of the points. The pressure pain hyperalgesia was not uniformly distributed since PPTs were lower in points over the proximal phalanx of the fingers and the thenar eminency as compared with those points located over the distal phalanx of the fingers. The decrease in PPT levels was associated with the intensity and the duration of the pain symptoms, supporting a role of both peripheral and central sensitization mechanisms in this pain condition.
Carpal tunnel syndrome (CTS) is a complex disorder associated with symptoms (pain and/or paresthesia) in the territory innervated by the median nerve of the hand. Although the etiology and pathology of CTS are under debate, there is some evidence involving the nociceptive system because different studies have reported functional deficits of nociceptive afferent in patients with CTS (1–4). More recent studies indicated additional involvement of central mechanisms. For instance, Zannete et al found that 45% of patients with CTS reported proximal pain (5) and spreading of their symptoms (6). Tucker et al (7) found a bilateral generalized increase in vibration thresholds in CTS demonstrating a generalized disturbance of somatosensory function rather than the existence of isolated peripheral neuropathy. Tecchio et al (8) and Napadow et al (9) found cortical remapping in the primary somatosensory cortex S1 in CTS patients that was correlated with patients' symptoms, supporting a role of central mechanisms in CTS.
Some studies had investigated nociceptive mechanisms by assessing mechanical hyperalgesia in deep tissues. For that purpose, pressure pain thresholds (PPTs) (10) have been investigated in different chronic conditions, e.g., whiplash (11, 12), fibromyalgia (13), work-related disorders (14, 15), tension-type headache (16, 17), low back pain (18), osteoarthritis (19), and lateral epicondylalgia (20). These studies reported the presence of widespread mechanical pain sensitivity as a sign of generalized central nervous system hyperexcitability or central sensitization. In fact, we have recently shown bilateral widespread pressure hypersensitivity in CTS subjects associated with pain intensity and duration of pain symptoms (21). In a previous study, we reported a significant decrease in PPTs bilaterally over peripheral nerves of the arm, the C5–C6 zygapophyseal joint, and the carpal tunnel and tibialis anterior muscle, suggesting multisegmental sensitization or central sensitization in unilateral CTS (21). Nevertheless, recent evidence has shown that pressure pain hypersensitivity is not uniformly distributed within a region, as spatial changes in pressure pain sensitivity have been found in the cephalic region in different headache disorders (22, 23) or shoulder pain (24, 25).We have demonstrated the utility of multisite recordings for PPT mapping leading to a new imaging modality of muscle pain sensitivity (22–25). This technique enables us to visualize nonuniformity in muscle pressure pain sensitivity and, therefore, deep tissue hyperalgesia in a specific location of the body.
Li et al have recently reported high-resolution topographical mapping of thermal sensitivity in the hand in healthy subjects, showing that thermal sensitivity distribution over the hand is highly heterogeneous (26). To the best of our knowledge, no published studies have previously investigated topographical pressure pain sensitivity maps of the hand in patients with strictly unilateral painful CTS. In this study, we hypothesized heterogeneous topographical pressure pain sensitivity maps of the hand in patients with strictly unilateral CTS compared with healthy subjects highlighting different levels of hyperalgesia.
Consecutive patients diagnosed with CTS by an experienced neurophysiologist (AM-P) from the Neurology Department of Fundación Hospital Alcorcón were screened for eligibility criteria. The inclusion criteria consisted of both clinical and electrophysiologic signs of CTS (27). The patients had to present with pain and paresthesia within the median nerve distribution. Furthermore, patients had to exhibit at least 3 of the 4 following clinical findings: increasing symptoms during the night, positive Tinel's sign reproducing patients' symptoms, positive Phalen's sign reproducing patients' symptoms, or self-perceived hand strength deficits. Symptoms should have persisted for at least 6 months and should be strictly unilateral in order to assess a chronic condition. It has been found that patients with CTS can present with subclinical or “non-discomfort” CTS in the unaffected hand (28). In order to exclude these clinical pictures, we asked for any symptom or discomfort (paresthesia) in both hands. Clinical examination should have been negative in one hand.
In addition, the electrodiagnosis study should have revealed deficits of sensory and/or motor nerve conduction following the recommendations of the American Association of Electrodiagnostic Medicine, the American Academy of Neurology, and the American Academy of Physical Medicine and Rehabilitation (29, 30). Patients diagnosed with moderate (abnormal median nerve sensory velocity conduction and abnormal distal motor latency) or mild (abnormal median nerve sensory velocity conduction and normal distal motor latency) CTS were included in the study. A median nerve sensory conduction velocity slower than 40 mm/second and a median distal motor latency greater than 4.20 msec were considered abnormal (29, 30). Sensory and motor conduction studies of radial and ulnar nerves were done to rule out radial or ulnar nerve involvement.
Patients were excluded if they exhibited any of the following criteria: 1) bilateral symptoms; 2) extreme/severe CTS; 3) any sensory or motor deficit for either the ulnar or radial nerve; 4) age >65 years; 5) history of wrist, upper extremity, or cervical spine trauma (whiplash); 6) previous wrist, upper extremity, or cervical surgery; 7) previously received a steroid injection; 8) multiple diagnoses for the upper extremity; 9) a history suggesting systemic disease is causing the CTS (e.g., diabetes mellitus, thyroid disease); 10) pregnancy; 11) a concomitant medical condition (e.g., rheumatoid arthritis, fibromyalgia); 12) involved with or seeking litigation at the time of the study; 13) presence of a score greater than 8 points on the Beck Depression Inventory II (BDI-II) (31); or 14) previous conservative (e.g., physiotherapy, electrotherapy) treatment.
Healthy control subjects were recruited from volunteers who responded to a local announcement and were excluded if they exhibited a history of upper extremity or neck pain, fractures, or any neurologic disorder. Healthy controls were matched on the basis of age and hand dominance. Matching for age was achieved by individually selecting the control subject with the closest available match for age of the patient with CTS, whereas hand dominance was controlled by matching the dominant arm, which was defined as the hand that the participants used for writing. Healthy controls received the same exploration as CTS patients related to depression and medication consumption. This study was supervised by the Department of Physical Therapy, Occupational Therapy, Rehabilitation and Physical Medicine, Universidad Rey Juan Carlos. The project was approved by the local human research committee (FHA-URJC 033). All of the subjects signed an informed consent form prior to their inclusion.
A numerical pain rating scale (where 0 = no pain and 10 = maximum pain) (32) was used to assess the current level of hand pain and the worst and lowest level of pain experienced in the preceding week. Patients were asked to draw the distribution of their pain on an anatomic map (33). The pain area was calculated (arbitrary units) with a digitizer (Acecad D9000; Acecad).
The Spanish version (34) of the Boston Carpal Tunnel Questionnaire (BCTQ) (35), a self-report measure of functional limitation and symptom severity, was also used. This questionnaire evaluates 2 domains: the functional status scale evaluates the ability to perform 8 common hand-related tasks, whereas the symptom severity scale includes 11 items assessing hand pain severity, numbness, and weakness at night and during the day. Each question is answered on a 5-point scale (where 1 = no disability and 5 = very severe disability). Each BCTQ score (range 1–5) is calculated from the average of the score of the individual questions included in each subscale, with higher scores indicating greater severity. The BCTQ has been shown to be valid, reliable, and responsive for patients with CTS (36).
The sample size determination and calculations were based on detecting at least clinically significant differences of 20% on PPT levels between both groups (37), with an alpha level of 0.05, a desired power of 80%, and an estimated interindividual coefficient of variation for PPTs of 20%. This generated a sample size of at least 16 participants per group.
A PPT is defined as the amount of pressure where a sense of pressure changes to pain (38). An electronic algometer (Somedic) was used to measure the PPT. The algometer consists of a 1-cm2 rubber-tipped plunger mounted on a force transducer. The pressure was applied at a rate of 30 kPa/second. The participants were instructed to press a switch when the sensation changed from pressure to pain. Three PPT measurements (intraexaminer reliability) were taken at each point with a 20-second interval in between 2 consecutive points, with randomization in the order of the points' assessments. The reliability of pressure algometry has been found to be high (intraclass correlation coefficient [ICC] 0.91, 95% confidence interval [95% CI] 0.82–0.97) (39). Averaged PPT values over the 30 locations were interpolated using an inverse distance weighted interpolation (40) for graphical purposes to have an easy reading of the PPT distribution over both hands. The inverse distance weighted interpolation consists of computing PPT values to unknown locations by using mean scores from the set of known PPT values and locations (41, 42).
The study protocol was the same for patients and controls. All of the examinations were performed in a quiet, draught-free, temperature- and humidity-controlled laboratory (mean ± SD temperature 24°C ± 1°C, relative humidity 25–35%). All of the participants had abstained from vigorous exercise on the previous day. The participants were not allowed to take analgesics or a muscle relaxant through the 72 hours prior to the examination. Subjects were asked to take a seated position on an examination bed. PPT levels were measured bilaterally over 30 locations (Figure 1A) on each hand by an assessor (CF-d-l-P) blinded to the subjects' conditions. All of the PPT measurements were done by the same assessor. Each location was marked with a pencil as thumb: distal phalanx (point 1), proximal phalanx (point 2), and thenar eminency (point 3); index finger: distal phalanx (point 4), middle phalanx (point 5), and proximal phalanx (point 6); middle finger: distal (point 7), middle (point 8), and proximal (point 9) phalanx; fourth finger: distal (point 10), middle (point 11), and proximal (point 12) phalanx; fifth finger: distal (point 13), middle (point 14), and proximal (point 15) phalanx; and head of the fifth (point 16), fourth (point 17), third (point 18), and second (point 19) metacarpal bones. For points 20–27, 2-cm equidistant points over each metacarpal bone were marked (20–24 over the second metacarpal bone, 21–25 over the third metacarpal bone, 22–26 over the fourth metacarpal bone, and 23–27 over the fifth metacarpal bone). Finally, one point over the lower end of the hypothenar eminency (point 28), over the carpal tunnel (point 29), and over the lower end of the thenar eminency (point 30) were also assessed (Figure 1A). The measured spots were located in the 3 dermatomes C6, C7, and C8 (Figure 1B).
We focused the main analysis on topographical pain maps investigating PPTs on each isolated points; moreover, a complementary analysis by dermatomes was also done. In such a way, PPT levels from those points (1–6, 19, 23, 27, and 30) located over the dermatome C6, those points (7–9, 18, 22, 26, and 29) located over the dermatome C7, and those points (10–17, 20, 21, 24, 25, and 28) located over the dermatome C8 were pooled.
Data were analyzed with the SPSS statistical package, version 14.0 (SPSS). Results are expressed as mean and 95% CI. The Kolmogorov-Smirnov test was used to analyze the normal distribution of the variables (c values greater than 0.05). Quantitative data without a normal distribution (i.e., pain history, pain area, current level of pain, and lowest and worst level of pain in the preceding 24 hours) were analyzed with nonparametric tests, whereas data with a normal distribution (PPT) were analyzed with parametric tests. The ICC was used to assess the intraexaminer reliability of PPT levels. A multilevel (mixed-effect) analysis of variance (ANOVA) was applied to detect differences in PPTs, with side (dominant/nondominant, symptomatic/nonsymptomatic) and assessed points (from 1–30) as within-subject variables and with group (patients or controls) as the between-subject variable. A three-way ANOVA test was used to evaluate the differences in PPTs, with dermatome (C6, C7, and C8) and side (dominant/nondominant, symptomatic/nonsymptomatic) as within-subject factors and with group (patients, controls) as the between-subject factor. Post hoc comparisons were done with the Bonferroni test. Finally, the Spearman's rank correlation (rs) test was used to analyze the association between PPTs, the clinical variables relating to symptoms, and the scales of the BCTQ. The statistical analysis was conducted at a 95% confidence level and a P value less than 0.05 was considered statistically significant.
One hundred two consecutive patients with CTS were screened between March 2008 and March 2009 for possible eligibility criteria. Finally, a total of 20 women ages 32–52 years (mean ± SD 43 ± 4 years) presenting with unilateral CTS satisfied all of the criteria and agreed to participate. The reasons for exclusion were bilateral symptoms (n = 40), fibromyalgia (n = 15), whiplash syndrome (n = 5), previous surgery (n = 14), pregnancy (n = 4), and diabetes mellitus (n = 4). In addition, 20 matched healthy women ages 32–51 years (mean ± SD 43 ± 3 years) without upper extremity symptoms were also included. There were no statistical age differences between cases and controls (P = 0.763). All of the participants were right hand dominant. Fifteen (75%) had their right hand affected and the remaining 5 (25%) had the left hand affected. None of the patients were taking any analgesic drug (antidepressants, γ-aminobutyric acid–ergic medications, or long-acting benzodiazepine) at the time the study was conducted.
The mean ± SD duration of hand pain was 3.4 ± 1.2 years (95% CI 2.4–4.4) and the mean ± SD pain area on the affected hand was 14.3 ± 6.5 cm2 (95% CI 11.3–17.4). The mean ± SD current level of hand pain was 5.6 ± 0.7 (95% CI 5.3–5.9) and the mean ± SD worst level of pain experienced in the preceding week was 7.5 ± 0.8 (95% CI 7.0–7.8), whereas the mean ± SD lowest level of pain in the preceding week was 3.0 ± 0.5 (95% CI 2.7–3.3). The mean ± SD BCTQ functional status scale score was 2.5 ± 0.6 (95% CI 2.2–2.8) and the mean ± SD BCTQ symptom severity scale score was 2.8 ± 0.5 (95% CI 2.6–3.1). A significant positive correlation between duration of pain history and current level of hand pain (rs = 0.5, P = 0.03) was found. No significant correlation between either scale (functional status or symptom severity) of the BCTQ and clinical pain features was found.
The intraexaminer repeatability of PPT readings ranged from 0.90–0.93 in patients and from 0.89–0.94 in controls, suggesting high repeatability of the PPT data. The SEM ranged from 5.3–7.2 kPa, depending on the assessed point.
The ANOVA detected significant differences in mean PPTs between groups (F = 95.9, P < 0.001), sides (F = 22.1, P < 0.001), and between measurement points (F = 13.3, P < 0.001). General post hoc comparisons revealed 1) lower PPTs for CTS patients compared with healthy controls in all of the measurement points (P < 0.001 for all measurement points) (Table 1); 2) higher PPTs in the affected arm within CTS patients and in the dominant side within controls when compared with the unaffected/ nondominant side (P < 0.01 for both); and 3) lower PPT levels in points over the proximal phalanx of the fingers (P < 0.01 for points 6, 9, 12, and 15) and the thenar eminency (P < 0.01 for points 3, 23, 30, and 27) as compared with points located over the distal phalanx of the fingers (points 1, 4, 7, and 10).
|Mean (95% CI) kPa|
|Patients with CTS||317.1 (303.1–331.1)|
|Healthy controls||458.1 (448.1–468.0)|
|Patients with CTS||278.1 (270.2–285.9)|
|Healthy controls||429.4 (419.6–439.2)|
|Patients with CTS||252.5 (241.3–263.6)|
|Healthy controls||394.1 (380.9–407.4)|
|Patients with CTS||279.1 (268.8–289.3)|
|Healthy controls||449.7 (438.8–460.7)|
|Patients with CTS||263.9 (246.7–261.2)|
|Healthy controls||442.0 (429.0–454.9)|
|Patients with CTS||253.9 (243.5–264.2)|
|Healthy controls||424.7 (411.6–438.0)|
|Patients with CTS||265.6 (255.7–275.6)|
|Healthy controls||458.3 (445.0–471.7)|
|Patients with CTS||260.9 (255.5–266.3)|
|Healthy controls||448.4 (436.9–460.0)|
|Patients with CTS||250.1 (238.0–262.3)|
|Healthy controls||426.3 (414.1–438.5)|
|Patients with CTS||285.2 (275.7–294.8)|
|Healthy controls||442.5 (429.4–455.6)|
|Patients with CTS||269.7 (261.9–277.5)|
|Healthy controls||444.1 (433.5–454.6)|
|Patients with CTS||254.6 (243.7–265.4)|
|Healthy controls||404.2 (391.7–416.6)|
|Patients with CTS||250.4 (243.7–257.2)|
|Healthy controls||446.7 (433.4–460.0)|
|Patients with CTS||268.7 (257.6–279.8)|
|Healthy controls||428.9 (417.8–440.1)|
|Patients with CTS||247.9 (236.9–259.0)|
|Healthy controls||415.4 (402.5–428.4)|
|Patients with CTS||268.4 (258.8–278.1)|
|Healthy controls||436.1 (425.6–446.5)|
|Patients with CTS||243.4 (233.5–253.3)|
|Healthy controls||433.5 (424.2–442.7)|
|Patients with CTS||266.4 (256.9–275.9)|
|Healthy controls||440.8 (433.2–448.4)|
|Patients with CTS||274.1 (267.3–281.0)|
|Healthy controls||444.0 (434.1–453.9)|
|Patients with CTS||255.2 (245.7–264.7)|
|Healthy controls||433.6 (423.5–443.7)|
|Patients with CTS||260.0 (251.0–269.2)|
|Healthy controls||433.7 (422.5–444.9)|
|Patients with CTS||251.5 (243.8–259.4)|
|Healthy controls||424.6 (410.7–438.5)|
|Patients with CTS||256.0 (245.9–266.0)|
|Healthy controls||413.7 (399.1–428.4)|
|Patients with CTS||266.7 (258.7–274.6)|
|Healthy controls||442.2 (430.6–453.8)|
|Patients with CTS||282.9 (272.2–293.7)|
|Healthy controls||454.9 (445.5–464.2)|
|Patients with CTS||265.4 (255.7–275.1)|
|Healthy controls||431.1 (420.7–441.5)|
|Patients with CTS||268.6 (256.4–280.8)|
|Healthy controls||413.1 (402.8–423.3)|
|Patients with CTS||279.0 (268.5–289.4)|
|Healthy controls||436.5 (426.6–446.5)|
|Patients with CTS||275.1 (266.7–283.4)|
|Healthy controls||463.0 (451.5–474.4)|
|Patients with CTS||251.4 (241.2–261.6)|
|Healthy controls||431.2 (419.1–443.4)|
|Mean (95% confidence interval) kPa|
|Symptomatic side||326.3 (302.5–350.1)|
|Nonsymptomatic side||307.8 (291.8–323.9)|
|Symptomatic side||290.5 (279.2–301.9)|
|Nonsymptomatic side||265.5 (257.1–274.0)|
|Symptomatic side||264.4 (245.1–283.7)|
|Nonsymptomatic side||240.5 (230.3–250.8)|
|Symptomatic side||282.7 (266.3–299.2)|
|Nonsymptomatic side||275.4 (261.8–289.0)|
|Symptomatic side||248.7 (238.1–259.4)|
|Nonsymptomatic side||259.2 (249.1–269.2)|
|Symptomatic side||262.5 (245.4–279.5)|
|Nonsymptomatic side||245.3 (233.2–257.4)|
|Symptomatic side||272.1 (257.6–286.7)|
|Nonsymptomatic side||259.2 (244.8–273.4)|
|Symptomatic side||264.0 (256.8–271.3)|
|Nonsymptomatic side||257.8 (249.3–266.3)|
|Symptomatic side||263.3 (241.9–284.6)|
|Nonsymptomatic side||236.9 (226.1–247.7)|
|Symptomatic side||292.9 (277.7–308.0)|
|Nonsymptomatic side||277.6 (265.7–289.5)|
|Symptomatic side||274.8 (261.7–287.9)|
|Nonsymptomatic side||264.6 (255.5–273.8)|
|Symptomatic side||246.0 (227.9–264.0)|
|Nonsymptomatic side||263.2 (250.5–275.9)|
|Symptomatic side||256.7 (247.8–265.7)|
|Nonsymptomatic side||244.2 (234.1–254.2)|
|Symptomatic side||281.2 (261.7–300.8)|
|Nonsymptomatic side||256.2 (247.0–265.4)|
|Symptomatic side||255.6 (237.4–273.8)|
|Nonsymptomatic side||240.3 (226.9–253.7)|
|Symptomatic side||274.6 (260.7–288.4)|
|Nonsymptomatic side||262.3 (248.2–276.4)|
|Symptomatic side||230.5 (222.2–238.7)|
|Nonsymptomatic side||256.3 (239.4–273.2)|
|Symptomatic side||268.4 (257.0–279.8)|
|Nonsymptomatic side||264.4 (248.1–280.7)|
|Symptomatic side||276.2 (268.2–284.0)|
|Nonsymptomatic side||272.2 (260.2–284.1)|
|Symptomatic side||245.2 (233.3–257.1)|
|Nonsymptomatic side||265.3 (250.8–279.7)|
|Symptomatic side||267.6 (256.3–279.0)|
|Nonsymptomatic side||252.5 (238.1–266.9)|
|Symptomatic side||255.7 (245.3–266.2)|
|Nonsymptomatic side||247.4 (235.1–259.6)|
|Symptomatic side||252.4 (236.2–268.6)|
|Nonsymptomatic side||259.6 (246.4–272.8)|
|Symptomatic side||269.0 (255.7–282.4)|
|Nonsymptomatic side||264.3 (254.5–274.2)|
|Symptomatic side||290.7 (273.9–307.5)|
|Nonsymptomatic side||275.2 (261.2–289.3)|
|Symptomatic side||270.7 (257.6–283.8)|
|Nonsymptomatic side||260.0 (245.1–275.0)|
|Symptomatic side||264.7 (244.5–285.0)|
|Nonsymptomatic side||272.5 (257.0–288.0)|
|Symptomatic side||274.2 (258.6–289.7)|
|Nonsymptomatic side||283.7 (268.7–298.8)|
|Symptomatic side||266.5 (254.3–278.7)|
|Nonsymptomatic side||283.7 (272.4–295.0)|
|Symptomatic side||245.7 (233.4–257.9)|
|Nonsymptomatic side||257.1 (240.0–274.2)|
In addition, significant interactions between group and point (F = 4.1, P < 0.001) and between group × point × side (F = 1.5, P = 0.02) were found. Within the patient group, the affected side showed higher PPTs in points 2 (P = 0.021), 3 (P = 0.019), 6 (P = 0.024), 9 (P = 0.012), 14 (P = 0.016), and 15 (P = 0.028), and lower PPT levels in points 12 (P = 0.031), 17 (P = 0.025), 20 (P = 0.034), and 29 (P = 0.021), compared with the unaffected side (Figure 2). Within the control group, the dominant side showed higher PPTs in points 8 (P = 0.022), 10 (P = 0.017), 11 (P = 0.029), 12 (P = 0.028), 17 (P = 0.020), and 18 (P = 0.028) compared with the nondominant side (Figure 3). Table 2 summarizes PPTs of each point for both sides (symptomatic or nonsymptomatic) within CTS patients, and Table 3 shows PPTs of each point for both sides (dominant or nondominant) within healthy controls.
|Mean (95% confidence interval) kPa|
|Dominant side||459.2 (445.8–472.5)|
|Nondominant side||456.9 (440.8–473.0)|
|Dominant side||431.0 (422.3–439.7)|
|Nondominant side||427.7 (409.2–446.3)|
|Dominant side||389.5 (368.0–411.1)|
|Nondominant side||398.7 (381.4–416.0)|
|Dominant side||453.6 (434.5–472.6)|
|Nondominant side||445.9 (433.3–458.5)|
|Dominant side||444.3 (424.5–464.1)|
|Nondominant side||439.6 (420.9–458.3)|
|Dominant side||420.5 (404.7–436.4)|
|Nondominant side||429.0 (406.5–451.5)|
|Dominant side||464.6 (443.7–485.5)|
|Nondominant side||452.1 (433.8–470.4)|
|Dominant side||459.9 (442.2–477.6)|
|Nondominant side||436.9 (422.4–451.5)|
|Dominant side||432.8 (415.6–449.9)|
|Nondominant side||419.8 (401.2–438.3)|
|Dominant side||465.3 (444.6–486.1)|
|Nondominant side||419.8 (410.5–429.1)|
|Dominant side||452.6 (437.6–467.6)|
|Nondominant side||435.5 (420.4–450.6)|
|Dominant side||411.7 (392.4–431.0)|
|Nondominant side||396.7 (379.8–413.5)|
|Dominant side||454.7 (433.9–475.5)|
|Nondominant side||438.7 (421.0–456.4)|
|Dominant side||433.9 (419.6–448.2)|
|Nondominant side||423.9 (405.8–442.1)|
|Dominant side||419.5 (398.8–440.2)|
|Nondominant side||411.4 (393.7–428.8)|
|Dominant side||439.8 (425.9–453.7)|
|Nondominant side||432.3 (415.6–449.1)|
|Dominant side||443.0 (434.2–451.7)|
|Nondominant side||424.0 (407.9–440.1)|
|Dominant side||451.4 (442.4–460.4)|
|Nondominant side||430.1 (419.1–441.1)|
|Dominant side||445.5 (432.9–458.1)|
|Nondominant side||442.6 (426.1–459.1)|
|Dominant side||432.9 (415.6–450.2)|
|Nondominant side||434.4 (422.1–446.7)|
|Dominant side||428.4 (410.4–446.3)|
|Nondominant side||439.1 (424.4–453.8)|
|Dominant side||424.3 (404.4–444.1)|
|Nondominant side||425.1 (403.7–446.4)|
|Dominant side||423.1 (397.8–448.3)|
|Nondominant side||404.4 (388.2–420.7)|
|Dominant side||444.2 (427.3–461.0)|
|Nondominant side||440.3 (422.7–457.9)|
|Dominant side||457.5 (442.9–471.9)|
|Nondominant side||452.3 (439.3–465.4)|
|Dominant side||436.0 (421.5–450.5)|
|Nondominant side||426.2 (410.3–442.1)|
|Dominant side||416.3 (399.4–433.1)|
|Nondominant side||409.9 (396.8–423.0)|
|Dominant side||432.7 (417.8–447.7)|
|Nondominant side||440.3 (426.0–454.7)|
|Dominant side||460.9 (441.8–480.0)|
|Nondominant side||465.1 (450.6–479.5)|
|Dominant side||424.5 (404.5–444.5)|
|Nondominant side||438.0 (423.0–453.0)|
The ANOVA revealed significant differences between groups (F = 93.1, P < 0.001), but not between dermatomes (F = 1.1, P = 0.4), for PPT levels. In such a way, patients with CTS showed lower mean ± SD PPTs (P < 0.001 for all) in all dermatomes (C6 affected: 271.4 ± 40.9 kPa, C6 unaffected: 265.5 ± 32.7 kPa; C7 affected: 265.8 ± 28.7 kPa, C7 unaffected: 258.5 ± 30.1 kPa; C8 affected: 266.1 ± 35.2 kPa, C8 unaffected: 262.0 ± 29.5 kPa) when compared with healthy controls (C6 dominant: 430.7 ± 42.2 kPa, C6 nondominant: 429.3 ± 39.7 kPa; C7 dominant: 447.1 ± 39.0 kPa, C7 nondominant: 436.5 ± 37.9 kPa; C8 dominant: 439.7 ± 38.2 kPa, C8 nondominant: 429.9 ± 35.3 kPa), but without differences between dermatomes.
Finally, significant negative correlations between duration of pain symptoms and PPTs were found over points 1, 3, 4, 6, 9, 14, 15, 20, 22, and 30 (−0.6 < rs < −0.5; P < 0.01) on the affected side and with PPTs over points 6, 15, 23, and 28 (−0.7 < rs < −0.6; P < 0.01) on the unaffected side. In such a way, the longer the duration of pain history, the lower the PPT levels.
In addition, mean pain intensity was also negatively correlated with PPT levels over points 4 (rs = −0.7, P < 0.001), 8 (rs = −0.45, P = 0.04), 18 (rs = −0.5, P = 0.01), 27 (rs = −0.45, P = 0.04), and 28 (rs = −0.6, P = 0.007) within the affected side, and with points 4 (rs = −0.55, P = 0.009) and 24 (rs = −0.6, P = 0.006) on the unaffected side. In such a way, the greater the pain intensity, the lower the bilateral PPT levels.
The current study showed the ability of topographical mapping of pressure pain sensitivity to detect bilateral pain hyperalgesia in patients with strictly unilateral CTS as compared with healthy controls. In addition, lower PPT levels were found at distant points, supporting the hypothesis of central sensitization in CTS. Importantly, the decrease in PPTs was associated with the intensity and the duration of the pain symptoms, supporting a role of the peripheral input in driving the central sensitization in CTS.
The bilateral hyperalgesia found in both hands in patients with strictly unilateral CTS suggests a generalized pressure hyperalgesia. In addition, we also found higher PPTs within the affected arm of the patients and within the dominant side in controls, which most likely reflect a side-to-side dominance of pressure pain sensitivity. Furthermore, higher PPT values at the symptomatic hand in patients with CTS may be related to sensory disturbances related to the symptomatic region, since these patients usually experience hypoesthesia or paresthesia. Nevertheless, despite side dominance, patients with unilateral CTS showed bilateral pressure hyperalgesia as compared with controls.
In fact, the generalized pressure hyperalgesia was supported by the fact that the PPT was not significantly different between dermatomes (C6, C7, or C8), in line with recent results obtained in osteoarthritis patients (43) suggesting that mechanical sensitivity is not related to particular sensitized segments. Our results disagree with those previously found by Li et al (26), who demonstrated that thermal sensitivities were not uniformly distributed within hand dermatomes, with C7 being more sensitive than C8 to cold stimulation. It is known that the size of the stimulated skin area, the skin thickness, and the thermoreceptive density of nociceptive receptors may be factors affecting thermal sensations. It may be that hand dermatomes may have differences in the density of thermoreceptive nociceptors, explaining the differences in cold stimulation. Nevertheless, the results of the current study do not show the same distribution for mechanical pain nociceptors since PPTs showed no significant difference between dermatomes, arguing for pain modality specificity.
Pressure pain hyperalgesia has been found to be related to specific anatomic locations, e.g., muscle belly versus musculotendinous junctions. Nie et al have reported that muscle belly locations had greater pressure pain hyperalgesia when compared with musculotendinous junctions in the upper trapezius muscle (25). Spatial differences in mechanical pain sensitivity can be explained by the fact that belly sites have greater thickness than musculotendinous ones (44). In parallel, underlying bone structures in the musculotendinous junctions can provide increased tissue hardness, resulting in generally higher PPT levels than those seen in muscle belly. Furthermore, differences in the density of group III and IV afferents among musculotendinous junctions and muscle belly (45) and different concentrations of inflammatory mediators such as neuropeptides, cytokines, and catecholamines (46) can also explain these differences in PPTs. We should also consider that the area of the algometer probe used in the present study was 1 cm2. PPTs are reported to decrease when the probe area is increasing from 0.5–2 cm2 (47). Therefore, changes in the probe area would also result in changes in the spatial summation of pressure pain due to potential overlap between pressure-sensitive receptive fields of the palm of the hand. Further studies are needed to delineate the effects of probe size in PPT topographical maps in both healthy and patient populations.
Our results demonstrated that pressure hyperalgesia is not uniformly distributed over the palm of the hand since PPTs were lower in points over the proximal phalanx of the fingers and the thenar eminency as compared with those points located over the distal phalanx of the fingers in both patients and controls. Lower PPT levels over the thenar eminency are expected since this region houses the muscles of the thumb. Additionally, it was also expected that the distal phalanx of the finger would have lower pressure hyperalgesia, since it is usually seen in clinical practice that distal points are less hypersensible to pain than proximal points.
Because pressure pain sensitivity is not uniformly distributed over the palm of the hand in both patients with CTS and controls, anatomic locations should be precisely determined for pressure sensitivity examinations in clinical and research applications.
Our results argue for further evidence of both peripheral and central sensitization mechanisms in CTS patients, since bilateral and generalized pressure pain hyperalgesia were found in patients experiencing unilateral symptoms. In fact, the involvements of peripheral and central sensitization mechanisms have also been reported in several local pain syndromes, e.g., work-related disorders (14, 15), tension-type headache (16, 17), low back pain (18), osteoarthritis (19), lateral epicondylalgia (20), or unilateral shoulder pain (24). This clinical evidence agrees with findings in animal models where unilateral localized musculoskeletal pain causes segmental sensitization of contralateral areas (48), which may explain our bilateral hyperalgesia in the unaffected hand. It is hypothesized that the presence of sensitization mechanisms in local pain syndromes suggests that sustained peripheral noxious input to the central nervous system can play a role in the initiation and maintenance of these sensitization mechanisms. In fact, in our study we found that the decrease in PPTs was associated with the intensity and the duration of the pain symptoms, supporting an interaction between peripheral and central sensitization mechanisms. Therefore, in patients with CTS, the compression of the median nerve in the carpal tunnel may act as a trigger factor for establishing a neurogenic inflammation on its nervi nervorum (49, 50), and therefore initiate different potent sensitization mechanisms.
Finally, we should recognize the limitations of this study. First, we only included women with mild to moderate CTS and with strictly unilateral symptoms. Previous studies have shown that women have a less efficient pain habituation and a greater susceptibility to the development of temporal summation of mechanically evoked pain (51)than men. Population-based epidemiologic studies with greater sample sizes including both men and women are needed to permit a more generalized interpretation of these results. Furthermore, pressure pain sensitivity can be influenced by psychological status (depression or anxiety), although this is unlikely because in the current study, patients with depression status were excluded (>8 points on the BDI-II). In addition, it is also possible that beliefs related to possible interventions (e.g., physical therapy) could influence the pressure-sensitive heterogeneity, although this is unlikely since all of the patients had never received treatment. Finally, it would be interesting to assess topographical pressure sensitivity maps in dermatomes innervated by spinal segments above or below those dedicated to the median nerve, i.e., the shoulder region (C5 nerve root), to confirm the presence of central sensitization in this patient population.
In conclusion, topographical mapping of pressure pain sensitivity in patients with strictly unilateral CTS showed significant generalized hyperalgesia. In addition, extrasegmental sites to the median nerve also showed hyperalgesia in patients with strictly unilateral symptoms, indicating sensitization. Furthermore, the hyperalgesia was associated with the intensity and the duration of the pain symptoms, supporting a role of the peripheral input to drive the central sensitization in CTS.
All authors were involved in drafting the article or revising it critically for important intellectual content, and all authors approved the final version to be submitted for publication. Dr. Fernández-de-las-peñas had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Study conception and design. Fernández-de-las-Peñas, Madeleine, Martínez-Perez, Arendt-Nielsen, Jiménez-García, Pareja.
Acquisition of data. Fernández-de-las-Peñas, Madeleine, Martínez-Perez, Arendt-Nielsen, Jiménez-García, Pareja.
Analysis and interpretation of data. Fernández-de-las-Peñas, Madeleine, Martínez-Perez, Arendt-Nielsen, Jiménez-García, Pareja.