Abstract
Background
Prior investigations into facial pain associated with chronic rhinosinusitis (CRS) have yielded important results, but have yet to utilize pain-specific outcome measures. This study seeks to characterize facial pain associated with CRS using validated pain-specific instruments.
Methods
Adults with CRS were enrolled into a prospective, cross-sectional study along with control participants presenting with non-CRS diagnoses. Facial pain was characterized in both groups using the Brief Pain Inventory Short Form (BPI-SF) and the Short-Form McGill Pain Questionnaire (SF-MPQ). CRS-specific measures of disease were measured including the Sinonasal Outcome Test-22 (SNOT-22), nasal endoscopy, and computed tomography scoring.
Results
Patients were comprised of CRS with nasal polyposis (CRSwNP; n=25), CRS without nasal polyposis (CRSsNP; n=30), and control participants (n=8). Subjects with CRSwNP and CRSsNP were less likely to be pain free than controls (16.0%, 6.7% and 62.5% respectively, p=0.001) and carried greater burden of pain as measured by the BPI-SF and SF-MPQ than controls (p=0.002 and p=0.017, respectively). Pain in CRS was most commonly located around the eyes and characterized as ‘throbbing’ and ‘aching’. Nasal polyp status was not associated with differences in character, severity, or location of pain.
Conclusions
Subjects with CRS have a greater burden of facial pain relative to control subjects across several standardized pain measures. Further, facial pain in CRS significantly correlated to QOL and CRS-specific disease severity measures. Study across larger cohorts using standardized pain measures is warranted to clarify the association of facial pain with chronic rhinosinusitis.
MeSH Key Words: sinusitis, facial pain, outcome assessment, data collection, endoscopy
INTRODUCTION
Two major chronic rhinosinusitis (CRS) guidelines include presence of facial pain as part of the clinical diagnostic criteria for CRS.1,2 However, the association of facial pain with CRS continues to be controversial, such that the EPOS guidelines highlight literature demonstrating that only a minority of subjects with CRS experience facial pain.2 The recommendation of including facial pain/pressure in the AAO-HNSF adult rhinosinusitis guidelines is based on a study reporting only on ‘facial pressure’ which highlights the wide range of terminology used to describe and connote pain by both patients and physicians.3,4 The caution of the EPOS guidelines and the ambiguity of the adult rhinosinusitis guidelines with the cited literature reflect the need for a systematic characterization of facial pain in subjects with CRS.
Prior investigations into facial pain and CRS have been limited by a lack of validated outcomes measures. Investigation of pain in the context of CRS has generally been undertaken by either reporting of ‘facial pain’ by patients,5,6 by extracting an item from a CRS-specific measure7,8 or using a visual analog scale.9 There is ambiguity in the reporting merely of the binary presence or absence of ‘facial pain’ inasmuch as patients may minimize or exaggerate symptoms when forced into one of these two options.5,6 Extraction of facial pain data from visual analog scales and CRS-specific measures are difficult to interpret because facial pain and facial pressure are often grouped together.7,9 Furthermore, this data is often reported in subjects that have elected surgical treatment,8,9 which may be a biased interpretation as prior study has shown that differential symptom burden is associated with therapeutic decisions.10,11
The goal of the present study is to provide an accurate characterization and frequency of facial pain in patients presenting to a rhinologic practice with CRS with and without nasal polyposis.
MATERIALS and METHODS
Patient Populations & Inclusion Criteria
Adult patients (≥18 years of age) presenting to the University of Utah, Sinus & Skull Base clinic with a current diagnosis of CRS, as defined by the 2007 Adult Sinusitis Guideline and endorsed by the American Academy of Otolaryngology-Head and Neck Surgery, were approached about study participation by the enrolling physician after completion of standard clinical appointments. Each patient had undergone previous treatment with oral, broad spectrum or culture directed antibiotics (≥2 weeks duration) and either topical nasal corticosteroid sprays (≥3 week duration) or a 5-day trial of systemic steroid therapy. The Institutional Review Board at the University of Utah provided annual review and approval for all study protocols (IRB #61810).
Study case participants provided informed consent and were required to complete all necessary enrollment procedures and pain scale questionnaires in English during the initial enrollment meeting. Each participant was also asked to report demographic, social/medical history data including: age, gender, household income, current tobacco use, alcohol consumption, nasal polyposis, depression by physician diagnosis, asthma, allergies (both by reported patient history or confirmed skin prick or modified radioallergosorbent testing), acetylsalicylic acid (ASA) intolerance, cystic fibrosis, obstructive sleep apnea (OSA), and a history of both prior sinus surgery and headache and/or facial pain. Subjects were stratified into CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP) as these phenotypes may represent heterogeneous inflammatory processes2 and prior study has suggested that subjects with CRSwNP do not have facial pain unless there is an acute bacterial infection.6
Study control participants with other head or neck disorders not associated with secondary head or facial pain (see exclusion criteria below) who presented to the Sinus & Skull Base clinic without evidence of CRS, on either computed tomography (CT) or visual endoscopy exam if indicated or had a clinical history inconsistent with CRS and did not require endoscopy or imaging, were approached about study enrollment. All consenting control participants were asked to provide the same demographic and social/medical history.
Exclusion criteria
Participants diagnosed with a concurrent exacerbation of recurrent acute sinusitis were excluded from final analyses due to the heterogeneity of the disease etiology. Study participants with a history of OSA or secondary headache and/or facial pain attributable to a medical condition other than CRS were excluded due to potential influences on pain scale questionnaires. All patients with comorbid disorders of the cranium, neck, eyes, ears, teeth, mouth, or cervical structures were excluded due to the potential influence of pain symptoms unrelated to CRS. In addition, all study participants who failed to complete all QOL and pain scale questionnaires during the initial enrollment meeting were excluded from final analyses.
Quality of Life and Pain Severity Questionnaires
Disease-Specific Quality of Life Measures
Participants completed the Sinonasal Outcome Test-22 (SNOT-22). The SNOT-22 is a 22-item test used to assess symptom severity of CRS.12 Lower total scores (range: 0–110) on the SNOT-22 indicate better overall QOL and symptom severity. Five distinct symptom domains of the SNOT-22 have been previously described and include rhinologic symptoms (range: 0–30), extra-nasal rhinologic symptoms (range: 0–15), ear/facial symptoms (range: 0–25), psychological dysfunction (range: 0–35), and sleep dysfunction (range: 0–25).13
Patient-Reported Sinonasal Pain Severity Measures
Participants were asked to complete two validated pain scales to evaluate sinus-specific pain severity. The Brief Pain Inventory Short Form (BPI-SF) is a validated and widely used tool to measure both clinical pain severity and interference across a variety of disease processes (e.g., low back pain,14 painful diabetic neuropathy,15 and temporomandibular joint dysfunction).16 Pain severity was evaluated by instructing patients to indicate, on a scale from 0 – 10, how severe current sinus pain is at its “worst (in past 24 hours)”, “least (in past 24 hours)”, “average”, and “right now”. The arithmetic mean of those four scores is calculated and reported (range: 0–10). Pain interference was evaluated by asking participants how much sinus pain interferes with daily activities including: general activity, walking ability, normal work, mood, enjoyment of life, relations with other people, and sleep on a 0 (“Does not interfere”) to 10 (“Completely interferes”) scale. Pain interference is reported as the mean of the seven interference items (range: 0–10). Higher scores represent more pain severity and interference. Additionally, participants were asked to designate the precise location of their sinus-related facial and/or head pain on a diagram that was modified to include only an enlarged diagram of the head instead of the entire body (Figure 1).
Figure 1.
Modified diagram for sinus-related facial and/or head pain. Yellow area, above right eye; Blue area, above left eye; Gray area, below right eye; Green area, below left eye; Red area, between eyes; Black area, top of head; Orange area, back of head; Brown area, right temple; Purple area, left temple.
Study participants were asked to complete the Short-Form McGill Pain Questionnaire (SF-MPQ) which consists of 15 pain descriptors ranked on a Likert scale from 0 (“None”) to 3 (“Severe”).17 The first 11 pain descriptor item scores are summarized (range: 0–33) to represent the sensory dimension of sinus-related pain (eg. throbbing, aching) while the remaining 4 descriptor item scores are summarized (range: 0–12) to represent the affective dimension of sinus-related pain (eg. fearful, sickening). The initial total score of the SF-MPQ can be calculated by adding the domain scores of the sensory dimension and affective dimension (range: 0–45). Additionally, the Present Pain Intensity (PPI) scale is used to indicate overall pain intensity by ranking current pain from 0 (“No pain”) to 5 (“Excruciating”). A final total score on the SF-MPQ can be calculated by adding the PPI to the initial total score (range: 0–50). In addition to the pain descriptors, the SF-MPQ includes a visual analogue scale (VAS) to provide an overall pain intensity measure that was modified to a Likert scale from 0–10 and again directed the subjects to refer to sinus pain.
Clinical Measures of Disease Severity
Study participants were evaluated for CRS disease severity using high-resolution computed tomography (CT) with bone and soft tissue windows and 1.0mm contiguous images in the coronal plane. Images were evaluated and staged by the enrolling physician in accordance with the Lund-Mackay bilateral scoring system (range: 0–24), with higher scores indicating worse severity of disease.18 This scoring system quantifies the degree of image opacification in the maxillary, ethmoidal, sphenoidal, ostiomeatal complex, and frontal sinus regions using a scale (0–1–2).
Study participants were also evaluated via endoscopic examinations using rigid, 30° endoscopes (SCB Xenon 175, Karl Storz, Tuttlingen, Germany). Endoscopic exams were scored by the enrolling physician using the bilateral Lund-Kennedy endoscopy scoring system (range: 0–20), which quantifies bilateral, pathologic states within the paranasal sinuses including the presence of: polyposis, discharge, edema, scarring, and crusting using the same standard scale (0–1–2). Higher total scores indicate worse visualized disease severity.19 The enrolling physician was blinded to all other study data when both clinical measures were scored.
Data Management, Sampling Size Estimations, and Statistical Analysis
Study data were collected using standardized clinical research forms, stripped of all protected health information, and manually entered into a relational database (Microsoft Access; Microsoft Corp., Redmond, WA) by a trained research coordinator. Statistical analysis was accomplished using a commercially available statistical software application (SPSS v.22, IBM Corp., Armonk, NY). Two-tailed sample size estimations (Table 1) were determined for correlation coefficients (R) between pain scale scores and other measures of disease severity, assuming 80% power (1-β error probability) and a 0.050 alpha (α) level. The current sample size is adequately powered to detect weak correlation coefficients (r >0.300) for most reported bivariate linear associations.
Table 1.
Sample size estimations for correlation coefficients (R) between pain-scale scores and outcome measures of disease severity
| R2 | Effect Size (R) | Sample Size |
|---|---|---|
| 0.200 | 0.447 | 34 |
| 0.250 | 0.500 | 26 |
| 0.300 | 0.547 | 21 |
| 0.350 | 0.591 | 17 |
| 0.400 | 0.632 | 14 |
| 0.450 | 0.671 | 12 |
| 0.500 | 0.707 | 11 |
| 0.550 | 0.742 | 9 |
R2; coefficient of determination
Descriptive and graphical analytics were used to assess all study variables and confirm assumptions of normality and distribution of continuous data. Chi-square (χ2) testing with both 2×2 and 2×3 contingency tables, Mann-Whitney U tests, and Kruskall-Wallis tests were used to evaluate differences in patient characteristics, reported QOL, and pain scale questionnaire scores between CRSsNP, CRSwNP, and control participants. Significant differences were determined using the 0.050 α level. Pearson’s correlation coefficients (Rp) or Spearman’s rank correlation coefficients (Rs) were used to evaluate potential linear associations between pain severity measures and all other continuous study covariates where appropriate.
RESULTS
Study Population Characteristics
A total of 63 study participants met all inclusion criteria and were enrolled in this prospective cross-sectional investigation between August, 2013 and August, 2014. This group was comprised of CRS with nasal polyposis (CRSwNP; n=25), CRS without nasal polyposis (CRSsNP; n=30) and control participants (n=8). The control patients consisted of patients with septal deviation in isolation (n=1), septal deviation in conjunction with bilateral inferior turbinate hypertrophy (n=5), asymptomatic sphenoid mucocoele (n=1), and encephalocoele (n=1). Six of 8 controls (75%) underwent CT, and 5 of 8 underwent sinonasal endoscopy (62.5%) as part of clinical evaluation. All patients with CRS underwent both radiography and endoscopy examinations. Overall patient characteristics across patient subgroups are described in Table 2. Control participants were significantly less likely to have comorbid allergies or a history of prior sinus surgery compared to both CRSwNP and CRSsNP, however the prevalence of allergy and prior sinus surgery between CRSwNP and CRSsNP groups was not significantly different from each other (p≥0.808).
Table 2.
Comparison of baseline characteristics of chronic rhinosinusitis study groups and controls
| Characteristics: | CRSwNP (n=25) | CRSsNP (n=30) | Controls (n=8) | p-value | |||
|---|---|---|---|---|---|---|---|
| Mean [SD] | N(%) | Mean [SD] | N(%) | Mean [SD] | N(%) | ||
| Age (years) | 43.6 [16.7] | 51.1 [16.7] | 43.8 [19.1] | 0.212 | |||
| Males | 16 (64.0) | 13 (43.3) | 4 (50.0) | ||||
| Females | 9 (36.0) | 17 (56.7) | 4 (50.0) | 0.308 | |||
| Depression | 3 (12.0) | 3 (10.0) | 1 (12.5) | 0.964 | |||
| Asthma | 12 (48.0) | 12 (40.0) | 1 (12.5) | 0.203 | |||
| Allergy | 14 (56.0) | 16 (53.3) | 0 (0.0) | 0.015 | |||
| ASA sensitivity | 6 (24.0) | 3 (10.0) | 0 (0.0) | 0.156 | |||
| Tobacco smoking | 0 (0.0) | 1 (3.3) | 1 (12.5) | 0.214 | |||
| Alcohol consumption | 9 (36.0) | 7 (23.3) | 3 (37.5) | 0.529 | |||
| Prior sinus surgery | 18 (72.0) | 20 (69.0)* | 0 (0.0) | <0.001 | |||
| Cystic fibrosis | 2 (8.0) | 0 (0.0) | 0 (0.0) | 0.217 | |||
Valid percentages are reported to account for any missing data.
CRSwNP, chronic rhinosinusitis with nasal polyposis; CRSsNP, chronic rhinosinusitis without nasal polyposis; SD, standard deviation; ASA, acetylsalicylic acid
Control participants reported significantly better disease-specific QOL scores compared to both CRSwNP and CRSsNP on the SNOT-22 total mean scores, rhinologic symptom scores, and ear/facial symptom scores, as well as significantly less disease severity as measured by CT and endoscopy scores (Table 3). When comparing bivariate differences in baseline QOL between CRSwNP and CRSsNP only the mean SNOT-22 rhinologic domain scores were significantly better in the CRSsNP subgroup (p=0.024). Likewise, CRSsNP were found to have significantly better mean CT scores (p<0.001) and endoscopy scores (p=0.004) compared to their CRSwNP counterparts.
Table 3.
Comparison of quality of life and disease severity measures of chronic rhinosinusitis study groups and controls
| QOL Scores: | CRSwNP (n=25) | CRSsNP (n=30) | Controls (n=8) | p-value |
|---|---|---|---|---|
| Mean [SD] | Mean [SD] | Mean [SD] | ||
| SNOT-22 Total Score | 56.2 [21.3] | 57.4 [17.3] | 31.9 [23.6] | 0.033 |
| Rhinologic symptom | 19.3 [4.6] | 16.6 [4.4] | 10.3 [6.6] | 0.001 |
| Extra-nasal rhinologic symptoms | 7.8 [3.5] | 8.3 [3.1] | 4.0 [5.3] | 0.057 |
| Ear/facial symptoms | 9.6 [6.0] | 11.1 [4.7] | 3.9 [3.7] | 0.005 |
| Psychological dysfunction | 16.4 [9.3] | 17.9 [7.7] | 10.9 [9.1] | 0.139 |
| Sleep dysfunction | 14.7 [6.5] | 14.9 [6.0] | 9.8 [8.6] | 0.277 |
| Clinical Measures of Disease Severity: | ||||
| Lund-Mackay CT Scores | 17.5 [4.8] | 9.5 [5.3] | 1.2 [1.6]* | <0.001 |
| Lund-Kennedy Endoscopy Scores | 7.4 [3.6] | 4.9 [2.4] | 2.0 [0.0]** | <0.001 |
CRSwNP, chronic rhinosinusitis with nasal polyposis; CRSsNP, chronic rhinosinusitis without nasal polyposis; SD, standard deviation; SNOT-22, 22-item Sinonasal Outcome Test; CT, computed tomography.
Data available for 6/8 control subjects.
Data available for 5/8 control subjects.
Pain severity scores were evaluated across all three study subgroups for both the BPI-SF (Table 4) and SF-MPQ (Table 5). Mean BPI-SF pain severity scores of the BPI-SF were significantly better in control subjects compared to CRSwNP (p=0.002) and CRSsNP (p<0.001) separately, however CRSwNP and CRSsNP were not significantly different from each other (p=0.549). Similarly BPI-SF pain interference scores were significantly better in control subjects compared to CRSwNP (p=0.002) and CRSsNP (p<0.001) separately, however CRSwNP and CRSsNP were not significantly different from each other (p=0.173). The prevalence of pain reported using the BPI-SF was found to be mostly located above and below the eyes in both the CRSwNP and CRSsNP groups (Table 4, Figure 2). No significant differences between CRSwNP and CRSsNP were found in the reported prevalence of any facial pain location as measured by the BPI-SF survey (all p≥0.092).
Table 4.
Comparison of Brief Pain Inventory Short Form (BPI-SF) Scores Between Chronic Rhinosinusitis Study Groups and Controls
| Pain Severity Measures: | CRSwNP (n=25) | CRSsNP (n=30) | Controls (n=8) | p-value | |||
|---|---|---|---|---|---|---|---|
| Mean [SD] | N (%) | Mean [SD] | N (%) | Mean [SD] | N (%) | ||
| BPI-SF Pain severity | 3.2 [2.0] | 3.6 [1.9] | 0.7 [1.1] | 0.002 | |||
| BPI-SF Pain interference | 2.7 [2.5] | 3.8 [2.8] | 0.4 [0.8] | 0.002 | |||
| Pain Location: | |||||||
| No pain | ---- | 4 (16.0) | ---- | 2 (6.7) | ---- | 5 (62.5) | 0.001 |
| Above right eye | ---- | 15 (60.0) | ---- | 16 (53.3) | ---- | 1 (12.5) | 0.060 |
| Above left eye | ---- | 15 (60.0) | ---- | 17 (56.7) | ---- | 1 (12.5) | 0.052 |
| Below right eye | ---- | 14 (56.0) | ---- | 16 (53.3) | ---- | 1 (12.5) | 0.083 |
| Below left eye | ---- | 15 (60.0) | ---- | 16 (53.3) | ---- | 1 (12.5) | 0.060 |
| Between eyes | ---- | 11 (44.0) | ---- | 17 (56.7) | ---- | 0 (0.0) | 0.016 |
| Top of head | ---- | 3 (12.0) | ---- | 5 (16.7) | ---- | 0 (0.0) | 0.449 |
| Back of head | ---- | 2 (8.0) | ---- | 8 (26.7) | ---- | 1 (12.5) | 0.178 |
| Right temple | ---- | 4 (16.0) | ---- | 10 (33.3) | ---- | 2 (25.0) | 0.339 |
| Left temple | ---- | 5 (20.0) | ---- | 12 (40.0) | ---- | 2 (25.0) | 0.259 |
Valid percentages are reported to account for any missing data.
CRSwNP, chronic rhinosinusitis with nasal polyposis; CRSsNP, chronic rhinosinusitis without nasal polyposis; SD, standard deviation; BPI-SF, Brief Pain Inventory Short Form
Table 5.
Comparison of the Short Form McGill Pain Questionnaire (SF-MPQ) Scores Between Chronic Rhinosinusitis Study Groups and Controls
| Pain Severity Measures: | CRSwNP (n=25) | CRSsNP (n=30) | Controls (n=8) | p-value | |||
|---|---|---|---|---|---|---|---|
| Mean [SD] | N(%) | Mean [SD] | N(%) | Mean [SD] | N(%) | ||
| Total SF-MPQ | 12.5 [11.0] | ---- | 11.7 [8.7] | ---- | 2.6 [4.6] | ---- | 0.017 |
| Sensory dimension | 9.5 [8.1] | ---- | 9.9 [7.3] | ---- | 2.3 [4.2] | ---- | 0.014 |
| Affective dimension | 3.0 [3.2] | ---- | 2.6 [2.1] | ---- | 0.4 [0.7] | ---- | 0.023 |
| PPI Score | 2.0 [1.2] | ---- | 2.1 [1.3] | ---- | 0.9 [1.2] | ---- | 0.071 |
| VAS Score | 3.5 [2.7] | ---- | 3.6 [2.5] | ---- | 0.5 [1.1] | ---- | 0.004 |
| Pain Descriptors: | |||||||
| Throbbing | 1.4 [1.0] | 18 (75.0) | 1.4 [1.0] | 23 (76.7) | 0.4 [0.5] | 3 (37.5) | 0.082 |
| Shooting | 0.7 [1.0] | 10 (43.5) | 0.7 [1.1] | 10 (35.7) | 0.3 [0.7] | 1 (12.5) | 0.289 |
| Stabbing | 0.9 [1.1] | 11 (47.8) | 0.9 [1.1] | 14 (48.3) | 0.1 [0.4] | 1 (12.5) | 0.167 |
| Sharp | 1.0 [1.0] | 14 (58.3) | 0.7 [1.0] | 10 (34.5) | 0.1 [0.4] | 1 (12.5) | 0.046 |
| Cramping | 0.5 [0.9] | 8 (33.3) | 0.2 [0.6] | 5 (17.2) | 0.0 [0.0] | 0 (0.0) | 0.104 |
| Knawing | 0.8 [1.1] | 9 (36.0) | 0.7 [1.0] | 12 (41.4) | 0.4 [1.1] | 1 (12.5) | 0.316 |
| Hot-burning | 0.4 [0.9] | 5 (20.8) | 0.7 [0.9] | 12 (42.9) | 0.3 [0.7] | 1 (12.5) | 0.115 |
| Aching | 1.6 [1.0] | 20 (80.0) | 1.3 [1.0] | 21 (72.4) | 0.4 [0.7] | 2 (25.0) | 0.012 |
| Heavy | 1.1 [1.1] | 15 (60.0) | 0.8 [0.9] | 16 (55.2) | 0.0 [0.0] | 0 (0.0) | 0.010 |
| Tender | 0.9 [0.9] | 13 (54.2) | 1.3 [0.9] | 23 (82.1) | 0.3 [0.7] | 1 (12.5) | 0.001 |
| Splitting | 0.9 [1.0] | 12 (50.0) | 1.1 [1.1] | 16 (57.1) | 0.1 [0.4] | 1 (12.5) | 0.082 |
| Tiring-exhausting | 1.4 [1.1] | 17 (73.9) | 1.4 [1.2] | 20 (69.0) | 0.3 [0.7] | 1 (12.5) | 0.005 |
| Sickening | 0.7 [1.0] | 10 (43.5) | 0.7 [0.8] | 14 (48.3) | 0.1 [0.4] | 1 (12.5) | 0.187 |
| Fearful | 0.4 [0.6] | 6 (26.1) | 0.2 [0.6] | 4 (14.8) | 0.0 [0.0] | 0 (0.0) | 0.219 |
| Punishing-cruel | 0.4 [0.9] | 5 (21.7) | 0.3 [0.6] | 7 (28.0) | 0.0 [0.0] | 0 (0.0) | 0.244 |
Valid percentages are reported to account for any missing data.
P-values for the pain descriptors compares the frequency of patients reporting each particular pain type across CRSwNP, CRSsNP, and control participants. CRSwNP, chronic rhinosinusitis with nasal polyposis; CRSsNP, chronic rhinosinusitis without nasal polyposis; SD, standard deviation; SF-MPQ, Short Form McGill Pain Questionnaire; PPI, Present Pain Intensity; VAS, visual analog scale
Figure 2.
Frequency and location of reported facial pain in study participants with chronic rhinosinusitis (n=55).
The impact of facial pain related to CRS was characterized further using the SF-MPQ scores between CRS subgroups and control participants (Table 5). Control participants reported significantly lower mean pain severity measures compared to CRSwNP and CRSsNP, while those two CRS subgroups did not report significantly different average scores for total SF-MPQ (p=0.991), sensory dimension (p=0.792), affective dimension (p=0.931), present pain inventory (p=0.934), or VAS scores (p=0.895). The frequency of participants reporting each type of pain descriptor was evaluated across CRSwNP, CRSsNP, and controls. The percentage of CRSwNP patients reported pain characterized largely as aching (80.0%), throbbing (75.0%), tiring-exhausting (73.9%), and heavy (60.0%). The percentage of CRSsNP patients reported pain characterized as tender (82.1%), throbbing (76.7%), aching (72.4%), and tiring-exhausting (69.0%). The only significant difference in the prevalence of pain descriptors on the SF-MPQ, between CRSwNP and CRSsNP, was a higher reported frequency of tender pain in the CRSsNP subgroup (p=0.038). All other pain descriptors were found to have similar prevalence between CRSwNP and CRSsNP (p≥0.083).
Bivariate correlation coefficients between clinical measures of disease severity and pain severity measures were compared for CRSwNP, CRSsNP, and control participants. No significant correlations were found between CT scores and any of the patient-reported pain severity scores for any subgroup (p≥0.206). Likewise, no significant correlations were found between endoscopy scores and any pain severity scores for either CRSwNP (p≥0.557) or CRSsNP (p≥0.171).
Bivariate correlation of total SNOT-22 scores revealed positive strong to very strong correlations (r = 0.482 – 0.735, p<0.050; Table 6) with all pain measures. Analysis of the SNOT-22 domains revealed that both subtypes of CRS demonstrate strong correlations between pain measures and the ear/facial, psychological, sleep domains (Table 6). In subjects with CRSsNP sinus-specific domains did not correlate (p>0.050) with pain measures with the exception of the ear/facial symptoms, which contains the item investigating ‘facial pain/pressure.’ In contrast, in subjects with CRSwNP there was strong correlation between the SNOT-22 rhinologic domain scores and BPI-SF Pain interference scores, total SF-MPQ scores, and both the sensory and affective dimensions of the SF-MPQ (r=0.483–0.557, p<0.050).
Table 6.
Bivariate correlation coefficients between SNOT-22 domain survey scores and pain severity measures within CRSwNP, CRSsNP, and controls
| CRSwNP - Pain Severity Measures: | SNOT-22 Scores | |||||
|---|---|---|---|---|---|---|
| Rhinologic symptoms R | Extra-nasal symptoms R | Ear/facial symptoms R | Psychological dysfunction R | Sleep dysfunction R | Total R | |
| BPI-SF Pain severity | 0.186 | 0.161 | 0.637* | 0.691** | 0.475* | 0.600* |
| BPI-SF Pain interference | 0.505* | 0.389 | 0.680** | 0.659** | 0.471* | 0.677** |
| Total SF-MPQ | 0.552* | 0.442* | 0.748** | 0.791** | 0.643* | 0.735** |
| Sensory dimension | 0.557* | 0.463* | 0.737** | 0.771** | 0.632* | 0.730** |
| Affective dimension | 0.483* | 0.392 | 0.732** | 0.796** | 0.574* | 0.716** |
| PPI Score | 0.315 | 0.204 | 0.587* | 0.569* | 0.359* | 0.491* |
| VAS Score | 0.355 | 0.321 | 0.659** | 0.752** | 0.518* | 0.669** |
| CRSsNP - Pain Severity Measures: | ||||||
| BPI-SF Pain severity | −0.001 | 0.007 | 0.412* | 0.613** | 0.564* | 0.482* |
| BPI-SF Pain interference | 0.231 | 0.075 | 0.355 | 0.760** | 0.720* | 0.711** |
| Total SF-MPQ | 0.360 | 0.207 | 0.588* | 0.726** | 0.598* | 0.639* |
| Sensory dimension | 0.238 | 0.231 | 0.575* | 0.684** | 0.463* | 0.604* |
| Affective dimension | 0.333 | 0.100 | 0.484* | 0.739** | 0.625* | 0.588* |
| PPI Score | 0.057 | 0.076 | 0.508* | 0.670** | 0.456* | 0.541* |
| VAS Score | 0.064 | 0.226 | 0.719** | 0.745** | 0.493* | 0.668** |
| Controls - Pain Severity Measures: | ||||||
| BPI-SF Pain severity | 0.456 | 0.553 | 0.588 | 0.125 | 0.452 | 0.495 |
| BPI-SF Pain interference | 0.408 | 0.309 | 0.257 | 0.158 | 0.592 | 0.514 |
| Total SF-MPQ | 0.498 | 0.553 | 0.695 | 0.167 | 0.369 | 0.454 |
| Sensory dimension | 0.466 | 0.571 | 0.689 | 0.138 | 0.345 | 0.436 |
| Affective dimension | 0.517 | 0.309 | 0.538 | 0.268 | 0.371 | 0.405 |
| PPI Score | 0.498 | 0.553 | 0.695 | 0.167 | 0.369 | 0.454 |
| VAS Score | 0.345 | 0.359 | 0.257 | 0.095 | 0.544 | 0.483 |
p-value <0.050;
p-value<0.001.
BPI-SF, Brief Pain Inventory Short Form; SNOT-22, 22-item Sinonasal Outcome Test; SF-MPQ, Short Form McGill Pain Questionnaire; PPI, Present Pain Intensity; VAS, visual analog scale; CRSwNP, chronic rhinosinusitis with nasal polyposis; CRSsNP, chronic rhinosinusitis without nasal polyposis;
DISCUSSION
The present study advances our understanding and characterization of facial pain in CRS. The majority of subjects with CRS in this cohort were burdened by facial pain relative to controls across several standardized pain measures. The pain associated with CRS manifests predominantly as a throbbing and aching pain around and between the eyes. Polyp status was not associated with differences in character, severity, or location of pain, although aching was most commonly reported in CRSwNP compared to tenderness in CRSsNP. Cumulative endoscopy scores and cumulative radiographic CT scores did not significantly correlate with the burden of pain severity.
The literature describing pain associated with CRS reports a wide range of prevalence. The discrepancy may be in part due to the treatment selection bias inherent in surgical cohorts. Such studies likely include subjects with higher burden or wide-ranging impact of disease compared to subjects that elect continued medical management as has been demonstrated in another North American cohort.10,11 Regardless, literature reporting pain in surgical cohorts tend to report pain8,9 or headache8,9,20 in the majority of subjects at baseline with significant improvements postoperatively. In contrast, cross-sectional studies evaluating subjects with CRS upon presentation report pain in only a minority of patients with CRS.5–7 These cross-sectional studies have been influential, and have shifted the perception that patients with chronic rhinosinusitis rarely have pain 2,5,21 unless experiencing an acute exacerbation.
The present study is the only cross-sectional study with a control group and yielded data that contradicts the prior cross-sectional studies. Subjects with CRS, regardless of polyp status, were burdened by pain at significantly higher levels than controls, and significantly higher than other published data on facial pain and CRS. In fact, rates of facial pain in prior studies are comparable to the controls in the present study.5–7 Although these prior studies are reporting rare pain in a minority of subjects with CRS, they are limited by a lack of validated instruments to accurately measure the pain and none compare to a control group. Use of validated pain instruments may increase sensitivity, providing subjects with a wider array of terms to discern and report pain related to CRS, and help explain the discrepancy between the present and prior studies. This discrepancy, though, highlights the fact that prior studies are either opaque in how pain information was extracted or are incomprehensive.5–7
Prior investigations have suggested that subjects with CRSwNP and CRSsNP tend to portray different symptom profiles. With regards to facial pain, Poetker et al22 reported that subjects with nasal polyposis experienced less pain than patients with CRSsNP on a VAS. There are also data suggesting that subjects with CRSwNP feel pain only in the context of viscid secretions and that absent viscid secretions facial pain is rare,5 again suggesting that different underlying pathophysiology manifest unique symptoms. The present study failed to find a significant association between subjects with and without polyposis, but a larger sample size might lead to the detection of a difference, as well as examination of the frequency of viscid secretion, which was not captured by the current study design (Table 1).
Unfortunately, little is known of the underlying mechanisms that produce pain associated with CRS, but several mechanisms that may all contribute to some degree to the manifestation of facial pain in CRS have been postulated. It has been hypothesized that occlusion of the osteomeatal complex may lead to gas resorption of the sinuses with painful negative pressures,23 yet most subjects with CRS have an open osteomeatal complex.24 Patients’ observations that pain and pressure is postural may reflect painful dilatation of vessels; 25 however, postural pain is also observed in subjects with simply tension type headache.25 Local inflammatory mediators can excite nerves locally within the sinonasal mucosa directly illiciting pain. For example, maxillary rhinosinusitis can cause dental pain through the stimulation of the trigeminal nerve.21 In addition, local tissue destruction and inflammatory mediators may influence the central mechanism of pain via immune-to-brain communication through afferent autonomic neuronal transmission, transport across the blood brain barrier through the circumventricular organs and/or direct passage across the blood brain barrier.27
The impact of inflammatory cytokines on the central nervous system have been associated with both pain as well as other health-related factors associated with chronic inflammation and sickness behavior such as disruption of sleep27 and mood.21 Interleukin-1[Beta] (IL-1[Beta]) and tumor necrosis factor-[alpha] (TNF-[alpha]) are two key pro-inflammatory cytokines with a pivotal role in the immune-to-brain pathway of communication. They are both upregulated in subjects with CRS28,29 and are two potential pro-inflammatory cytokines that have been implicated in fatigue,30 sleep dysfunction,27 depression,31 and pain.32 Characterizing the differential cytokine profiles of CRS subtypes and identifying associated symptom profiles may be an important step in understanding why some subjects experience greater health-related burden of disease,27 which is an important predictor of electing surgical intervention over continued medical therapy.10
The present study found significant correlations between measures of pain with CRS-specific QOL measures (Table 6), specifically in the psychologic and sleep domains. There was also a strong correlation between pain measures and the ear/facial symptoms domain, which was expected given that the item of ‘facial pain/pressure’ falls into this domain. The correlation of pain with the sleep and psychologic burden is not unexpected either. The recognition that pain and depression correlate has been recognized in the dental, orthopedic and gynecologic literature.34 The association is known as the depression-pain dyad given that they often are comorbid, exacerbate each other, and share common biological pathways.34 Understanding how CRS symptoms fuel depression and pain will help improve treatment algorithms and outcomes. Future study will also need to factor in the impact of other health-related issues that both impact and are influenced by pain, such as sleep quality and mood, and the underlying mechanisms that contribute this set of symptoms.
The current study has begun to improve our understanding of facial pain and CRS, and found that when using pain-specific instruments indeed the majority of subjects with CRS experience pain greater than controls. These findings raise a number of important questions for further study including the correlation of various inflammatory cytokines with symptoms of pain as well as the interplay of mood and sleep dysfunction on pain in CRS. Furthermore, the introduction of validated pain instruments into the rhinology literature may help to better clarify the symptom profile nuances that could potentially distinguish patients with migraine from patients with pain secondary to CRS. An improved understanding of these issues will help refine medical and surgical therapies for patients that suffer from these most debilitating symptoms of CRS as well as assist in our understanding of how those therapies improve facial pain associated with CRS.
CONCLUSIONS
Subjects with CRS commonly experienced pain in this cohort in contrast to prior cross-sectional studies. This pain was most commonly described as a throbbing and aching sensation around the eyes. No difference was identified between subjects with and without nasal polyposis. Pain burdens correlated with total SNOT-22 scores, and specifically the domains investigating sleep and psychological impairments associated with the disease. Future study investigating the impact of comorbid sleep, depression, and pain as well as the underlying cytokine profiles associated with these most debilitating symptoms may help refine patient therapies and expectations.
Footnotes
Conflict of interest: Timothy L. Smith, Jess C. Mace, and Jeremiah A. Alt are supported by a grant from the National Institute on Deafness and Other Communication Disorders (NIDCD), one of the National Institutes of Health, Bethesda, MD (R01 DC005805; PI/PD: TL Smith). Public clinical trial registration (www.clinicaltrials.gov) ID# NCT01332136. Timothy L. Smith and Adam S. DeConde are consultants for IntersectENT, Inc (Menlo Park, CA) which is not affiliated with this investigation. Richard R. Orlandi is a consultant for Medtronic ENT (Jacksonville, FL) which is not affiliated with this research.
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