The Effect of Pressure Pain Sensitivity and Patient Factors on Self-Reported Pain-Disability in Patients with Chronic Neck Pain

INTRODUCTION

Neck pain (NP) is a common musculoskeletal pain disorder [1, 2]. Almost everyone experiences NP at some point in his or her lifetime [3] with a yearly prevalence estimated at roughly 30-50% in the general population [4-7]. Reported incidence and prevalence figures of NP may vary according to patient factors (e.g. age, gender, and comorbidity). The prevalence of pain is reportedly greater among females and older persons [5, 8]. A recent review suggested that gender can influence pain [9] and being female might be associated with higher prevalence and pain intensity. A systematic review reported that the prevalence of NP declines after middle age [10]. Another study suggests an important association between comorbidities and NP [11]. Moreover, it has been demonstrated that accumulated comorbid load is independentlyassociated with chronic pain [12]. This provides a rationale for considering patient factors, including comorbidity, in the assessment of pain-related disability in patients with chronic NP.

NP and its associated disability are a tremendous financial burden to most industrialized nations [13]. The under pinning etiology of NP can be illusive [1]. Evidence suggests it is more closely associated with sensory disturbances than degenerative and radiological findings [14-17]. A large community based British study [18] supported the importance of neurological factors in NP.Poor recovery in NP is associated with widespread sensory hypersensitivity [19, 20]. Research studies [21, 22] and a systematic review [23] have demonstrated evidence of central hyperexcitability in musculoskeletal pain. Generalized sensory hyposensitivity (hypoesthesia) and/or hypersensitivity (hyperesthesia) is a feature in a subset of chronic NP [24]. Abnormal sensory findings are prognostic of poorer clinical outcomes for chronic pain conditions [24, 25] thereby providing substantial rationale for including sensory evaluation in the assessment of patients with NP.

Psychophysical quantitative sensory testing (QST) provides a means for semi-objective measurement of both hypo and hyper-sensory function [25, 26]. QST has the potential to contribute to the assessment of NP conditions if it can be shown to help with diagnosis, treatment selection, or prognosis. Mapping of the anatomical distribution of sensory changes (e.g. hypoesthesia) may be one factor identifying the pathological source in peripheral nerve, plexus, root and central tissues (spinal or cerebral) [26]. QST was associated with neck disability in patients with NP [27]. QST has many demonstrated uses in clinical practice [28-30].

Pressure pain sensitivity (PPS) measures are a reliable QST technique for the assessment of pressure (mechanical) pain sensitivity of deep somatic structures in the neck area [31, 32]. PPS measure using algometry is relatively inexpensive and feasible test method. The PPS test protocol is based on the “method of levels” parameter of QST techniques where pressure level is determined by a forced choice option (e.g. yes/no). In this way PPS can target peripheral small fiber based sensory/pain channels (e.g. Aδ, C nerve fibers) [25, 33, 34]. Alterations of pain processing mechanisms (both peripheral and central) may manifest as a reduction in PPS [35].

There are two common test sites on the cervical spine for somatosensory characterization of patients with NP [36-38] - the C2 paraspinal muscles and the upper trapezius muscle. Self-reported physical activity of NP population was related to PPS at these two common testing sites of neck muscles [39]. The upper trapezius pressure pain threshold value has high reliability (minimum detectable change = 0.48 kg/cm²) in patients with NP [40]. PPS measures over the C2-C3 and C5-C6 cervical zygapophyseal joints correlate with lower activation of the semispinalis cervicis muscle as quantified by intramuscular electromyography (at the levels of C2 and C5 during NP)[41]. Studies of PPS indicate that women were more sensitive than men to pressure pain stimulation in cervico-thoracic areas [42]. Pressure pain threshold was positively associated with muscle strength in healthy individuals [43]. Clinically, PPS measures over bony sites (e.g. tibia) were lower in patients with musculoskeletal pain compared to the healthy population [44] and were used to indicate central sensitization. Moreover, since the periosteum (innervated by unmyelinated small fibers) is sensitive to pressure stimulation [45, 46], the tibial shaft was used to assess periosteum sensitivity.

At present there is insufficient evidence about the relationship between PPS and pain-related disability and which patient factors (e.g. age, gender, and comorbidity) might mediate the relationship. The main objective of this study was to estimate the extent to which the PPS test (threshold and tolerance in selected locations) and patient factors predict pain- related disability in patients with chronic NP. The second objective was to estimate the effect of gender on PPS measures, particularly threshold and tolerance, for this patient population. The final objective was to determine if there were gender differences for self-reported pain-disability and comorbidity in this patient population.

MATERIALS AND METHODS

RESULTS

The bivariate relationships between PPS and pain-disability are shown in Table 2. These correlations indicate that greater PPS (both threshold and tolerance) was significantly associated with less pain-disability (r = -.35 to -.53, p ≤ 0.01). PPS at the level of C2 was significantly correlated with the total pain rating index of SF-MPQ (r = -.31 to -40, p ≤ 0.05). Age was not correlated with pain-disability, whereas greater comorbidity was correlated with higher pain-disability (r = 0.42-.43, p ≤ 0.01).

Table 3 indicates that when multiple PPS test variables were entered as potential predictors of neck disability outcomes all PPS variables (at 4-selected test locations) were significant predictors (p < 0.03). The total variability explained by all PPS variables range from 25% to 28%. Table 4 indicates that when patient factors (age, gender and comorbidity) were considered in a multivariate model of NP-disability outcomes, comorbidity was the most consistent predictor that was significantly related to neck disability and evaluative pain. In these multivariate models, comorbidity (p < 0.01) was associated with higher pain (in rating, intensity and evaluation). The amount of variability explained by the overall R² for these models range from 13% to 30%.

Significant mean differences in gender (male>female) were found in most PPS tests (1.2-5.4, p < 0.05), with a few exceptions (mainly at C2 level) (Table 5). Significant mean differences for gender (male<female) were found in the self-reported disability (18.5, p = 0.003) and comorbidity score (2.1, p = 0.03) (Table 6). However, self-reported pain dimensions (SF-MPQ) were independent of gender.

DISCUSSION

This study provided preliminary evidence suggesting that both pain threshold and tolerance affect pain-disability, as indicated by medium to large size bivariate correlations. The impact of PPS was further evident in multivariate modeling where individual PPS (at four test locations) explained 25 to 28% of neck disability. Conversely, when age, gender and comorbidity were entered into multivariate models, although higher R²’s were not achieved, comorbidity was the primary determinant of pain-disability. This suggests that the role of comorbidity in pain-related disability may partially be related to the extent to which it sensitizes the pain-neurophysiology of the individual.

Male participants demonstrated higher pain threshold and tolerance. However, gender was not associated with differences in pain dimensions when multivariate modeling was considered. Previous studies found that pressure pain threshold was lower in women than men [59,60]. Moreover, it was demonstrated that self reported NP was higher among women than men [4,5]. Our study suggested that pressure pain tolerance was also gender dependent. Gender was acknowledged as an important consideration in NP conditions because of differences in prevalence of different NP conditions by gender. The prevalence and incidence of NP is higher in females than males [65]. Furthermore, gender differences in pain threshold and tolerance was well accepted [66,67]. This study also demonstrated that PPS measures (threshold and tolerance) was more sensitive (lower threshold and tolerance) in females. Females also had more pain-related disability and comorbid health conditions. As gender influences the PPS scores obtained, multivariate models should be powered sufficiently to allow for separate modeling of males and females to identify the true impact of PPS on outcomes or, at minimum, sufficient power to allow for gender interactions to be tested. The relatively small sample precluded testing interactions between PPS and other variables in a gender specific analysis.

Prevalence of NP declines after middle age (i.e. 60 years of age) [10], with middle-aged individuals having more than a two-fold risk of developing NP compared to younger aged individuals [61]. A recent study reported that age was an important moderator between pain and cognition relationships [62]. Although, we did not assess cognition in this study, we did not find age to be related to pain or disability. Similarly, whereas others have found age to be associated to QST [63] and pressure pain threshold [60], we did not find a similar relationship.

Dominick et al. demonstrated that accumulated comorbid load was independently associated with chronic pain in a large population based study [12]. Recently, Johansen et al. speculated that painful comorbid conditions influence pain sensitivity based on findings from their large population-based study of pain and health status determined by medical examination [60]. That study and our findings concur about the potential importance of comorbid health conditions to “prime” the pain system.

One of the main limitations of this study was that our sample was too small to explore more variables and their interactions. PPS measures provide somatosensory information based on stimulus-response parameters, and are limited by semi-objective psychophysical evaluation. A recent review suggested that it was preferable to assess both sensory and modulatory elements of pain sensitivity [9]. The type of stable threshold-based pain sensitivity measure used in this study provided limited information on complex pain processing since the measure was based on the static parameter of QST [26, 64]. It was suggested that dynamic QST may be better at assessing spatial and temporal summation as well as descending modulation of pain [9, 26]. In addition, suprathreshold pain processing can be assessed by the magnitude rating for a suprathreshold stimulus [9, 26]. We used threshold and tolerance parameters for the QST measures in this study because these are commonly used in clinical practice. Our findings reaffirmed the importance of PPS and patient factors in explaining pain-disability. Stimulus intensity/magnitude rating parameters of QST may be more relevant to clinical features (e.g. pain, disability).

The greater sensitivity of females to pain threshold and tolerance may reflect differences in how sensory inputs are received at the tissue level or how they are processed from the periphery to the brain. However, this study indicated that gender differences in pain threshold and tolerance was not necessarily indicative of gender differences in all NP-related health outcomes, including self-reported pain. This differential suggested that gender needs to be carefully considered when examining NP, and that all hypotheses should be tested separately between male and female subjects to assure that conclusions made apply across genders. However, sex/gender differences in pain processing may not necessarily lead to differences in the pain experiences or related disability. Differences in pain processing may be a reason for differences in treatment response. Again, these requirements suggested the need for larger sample sizes; and prespecified gender analyses.

CONCLUSION

This descriptive cross-sectional study suggested that PPS (both threshold and tolerance) may play a role in self-reported outcome measures (e.g. pain and disability) in NP. However, given the findings that PPS tests was gender dependent, and comorbidity also affected these outcomes, these observations must be considered with caution until larger samples are used to confirm any interactions between comorbidity and PPS measures. Future studies that investigate the effects of PPS or other indicators of pain processing in humans should consider both gender and comorbidity as potential confounders and be powered sufficiently to test/control for their effects and to run analyses in subgroups to insure that findings are generalizable. This is certainly important before the potential role for PPS to provide useful information in managing NP can be determined. Future studies may consider using alternative sensory evaluations including dynamic QST and pain magnitude ratings (for a suprathreshold stimulus) to elucidate the relationship between suprathreshold pain processing, descending control or central integration of pain and other clinical features of NP.

CONFLICT OF INTEREST

We, the authors of the manuscript, do not have a direct/indirect financial relation with the commercial/non-commercial identities mentioned in the paper that might lead to a conflict of interests.

REFERENCES