Abstract
Objective:
Pelvic floor pain, abdominal wall pain, and central nervous system pain amplification can be contributing factors in chronic pelvic pain (CPP), however; limited research has investigated the association of pelvic floor, abdominal, and uterine tenderness with central nervous system pain amplification. We assessed whether pressure pain thresholds on the non-dominant thumbnail, a marker of central nervous system pain amplification, were associated with pelvic floor, abdominal, and uterine tenderness among women with endometriosis or CPP.
Study Design:
We conducted a cross-sectional study among 88 females with endometriosis and/or CPP. Abdominal (6 locations), pelvic floor (6 locations) and uterine (1 location) tenderness were assessed via a standardized physical exam. Participants reported their pain levels (0–10 scale) with application of 2 kg of pressure at each area, with a pain rating of ≥4 on the 0–10 scale considered moderate to severe pain. Pain sensitivity was measured on the non-dominant thumbnail by applying discrete pressure stimuli using a previously validated protocol.
Results:
Overall, 50% (44/88), 42% (37/88), and 58% (51/88) of participants reported high pelvic floor, abdominal, and uterine tenderness, respectively. Pressure intensities needed to elicit ‘faint’ and ‘mild’ pain were lower for participants with high vs. low pelvic floor tenderness (median intensity for ‘faint’ pain=0.50 kgf/cm2(min-max:0.25–3.25) vs. 1.06(0.25–3.00), p-value=0.006; median intensity for ‘mild’ pain=2.00(0.63–4.88) vs. 2.63(0.75–6.00), p-value=0.03). No association was observed between pressure pain sensitivity and abdominal or uterine tenderness (p>0.11). Participants with endometriosis without pain were less likely to have high pelvic floor (22.2%), abdominal (11.1%), and uterine (25.9%) tenderness compared to participants with endometriosis with pain (63.0%, 50%, 65.2%, respectively) and participants with chronic pelvic pain (60%, 73.3%, 93.3%, respectively).
Conclusions:
These results suggest that high pelvic floor tenderness among women with endometriosis/CPP may be a marker of heightened pain sensitivity suggestive of central nervous system pain amplification and may impact treatment response. Future research should examine whether this clinical phenotype predicts response to medical and behavioral treatments (e.g, anti-convulsants, behavioral therapy, Physical Therapy).
Keywords: generalized nociceptive hypersensitivity, pressure pain sensitivity, quantitative sensory testing, nociplastic pain, endometriosis, chronic pelvic pain
1. Introduction
Chronic pelvic pain (CPP) affects approximately 6–25% of reproductive-aged women and up to 70% of women with CPP will also have identifiable endometriosis.[1,2] While the mechanisms underlying CPP are not fully understood, it is thought that in some individuals with CPP, pain is caused (entirely or in part) due to peripheral or central nervous system (CNS) sensitization rather than as solely a direct result of endometriosis or other pelvic pathology – termed nociplastic pain by the International Association for the Study of Pain.[3] Abdominal wall and pelvic floor myofascial pain are known contributors to CPP, including among women with endometriosis.[4] However, it is currently unknown how abdominal and pelvic floor pain among CPP patients relates to CNS pain amplification.[5,6]
One assessment method of CNS sensitization or pain amplification is through the evaluation of evoked pain sensitivity at body sites distant from the clinical pain site, a form of Quantitative Sensory Testing (QST). QST research has highlighted variability in pain sensitivity and modulation as a risk factor for chronic pain development.[7–9] Previous studies have noted lower nonpelvic and abdominal/pelvic pressure pain thresholds (PPTs) among endometriosis and CPP patients compared to healthy controls,[10–13] including research among the current study population.[11] Additionally, CPP patients have been shown to have lower pelvic floor muscle PPTs and higher pelvic floor muscle tenderness compared to healthy controls.[14] Recently, Phan et al (2021) reported that women with endometriosis-associated CPP had widespread pelvic floor myofascial dysfunction with low PPTs and palpable myofascial trigger points at pelvic floor muscles.[15] Additionally, the authors reported that endometriosis participants reporting diffuse pelvic pain were more likely to have at least 10 painful body territories, suggestive of widespread pain sensitization, compared to participants reporting local pain. However, it is not known how these two factors, nonpelvic PPTs and pelvic floor muscle tenderness relate to each other among women with CPP and endometriosis and no research has been conducted to assess pelvic floor muscle tenderness among endometriosis patients. Given that standard treatments for endometriosis, CPP, and pelvic floor myofascial pain (e.g. physical therapy) do not benefit all patients, a better understanding of the relationship between pelvic and abdominal tenderness and CNS pain amplification are necessary to identify personalized treatment plans for women with CPP and endometriosis.
In order to identify simple clinical findings that may be correlated with central sensitization and thus help guide treatment decisions, we sought to determine if patients with increased pelvic floor, abdominal and uterine tenderness have lower pressure pain thresholds on the non-dominant thumbnail among women with endometriosis or CPP. Additionally, we assessed the relationship of pelvic floor, abdominal, and uterine tenderness with quality of life and symptom severity including dysmenorrhea, dyspareunia, and dysuria.
2. Materials and Methods
2.1. Study Participants
The present analyses are a secondary analysis of the data presented in As-Sanie et al 2013 (refer to this paper for the full study details).[11] These analyses were limited to women with CPP or endometriosis. Premenopausal women aged 18–50 years, with CPP or surgically-confirmed endometriosis, and pelvic surgery within the last five years to confirm the presence or absence of endometriosis, were recruited between June 2006 and April 2010.[11] Participants were recruited from a tertiary-care endometriosis and pelvic pain referral center in addition to advertisements in the local community. Women who were pregnant, lactating, or menopausal, or who had a history of hysterectomy or oophorectomy were excluded from participation. Approval for this study was obtained from the University of Michigan Institutional Review Board and all participants provided signed informed consent.
2.2. Surgical, Medical and Demographic Information
Participants completed standardized questionnaires to assess demographics, medical history including surgical history and medication use, menstrual patterns, reproductive history, and pelvic pain history including severity, pattern, and symptom characteristics. Participants numerically rated the severity of their pelvic pain from 0–10 (0 = no pain, 10 = worst imaginable pain), and reported the average number of days per month in which they suffered from moderate to severe pelvic pain (defined as ≥4 on the 0–10 pain scale). Additionally, participants completed the Endometriosis Health Profile (EHP)-30[16,17] and the McGill Present Pain Intensity scale.[18] Body mass index (BMI) was calculated as weight (in kg) divided by height (in meters) squared.
An author blinded to all study data and with expertise in surgical evaluation of gynecologic disorders (SA) reviewed the most recent operative reports for all endometriosis and CPP participants. Pathology results were not required, but were used when available. Endometriosis was staged in accordance with the revised American Fertility Society endometriosis scoring system.[19] Participants were categorized into three groups as previously described: (1) endometriosis with ≤4 days of moderate to severe pelvic pain per month (EndoØPain), (2) endometriosis with >4 days of moderate to severe pelvic pain per month (Endo+Pain), and (3) CPP without endometriosis (CPPØEndo). As previously defined by this group, CPP is moderate to severe pelvic pain lasting ≥6 months and occurring ≥14 days monthly.
2.3. Nonpelvic Pressure Pain Sensitivity
All participants underwent pressure pain sensitivity testing by a blinded researcher. Testing was conducted using the multiple random staircase method on the non-dominant thumbnail as previously described by our group.[11] Initially, discrete pressure stimuli were applied to the thumbnail using a 1-cm2 rubber probe in an ascending pattern starting at 0.25 kgf/cm2 and increasing by 0.25–0.5 kgf/cm2 steps until reaching each participant’s individual pain tolerance or 10 kgf/cm2. Perceived pain intensity for each pressure stimuli was measured using the Gracely Box Scale (GBS), a 0–20 numerical descriptor scale.[20] Response-dependent multiple random staircase pressure application was then applied to the non-dominant thumbnail to determine the pressure stimulus intensity (kgf/cm2) needed to elicit “faint” pain (0.5 on GBS), “mild” pain (7.5 GBS), and “slightly intense” pain (13.5 GBS).[21] Participants were asked to abstain from opioid analgesic use for at least 48 hours prior to their study visit and testing was performed between days 2 and 10 of the menstrual cycle, to limit hormonal variability.
2.4. Standardized Abdominal and Pelvic Exam
All participants underwent a standardized physical exam to assess abdominal, pelvic floor, and uterine tenderness using a standardized case report form and conducted by the same physician (SA) who was blinded to the patient’s questionnaire data and pelvic pain status. Approximately 2 kg of pressure was applied using a single digit to four abdominal quadrants (right upper, left upper, right lower, and left lower), as well as the umbilicus and suprapubic areas. Participants reported each abdominal area to be either tender or nontender. An internal, single digit exam was then used to assess uterine tenderness and pelvic floor tenderness at the bilateral pubococcygeus, iliococcygeus, and coccygeus muscles. As previously described by Tu et al, the pelvic floor muscle locations were defined as follows: pubococcygeus is located anteromedial to the tendinous arch; iliococcygeus is located medial to the tendinous arch; coccygeus is located posteromedial to the ischial spine.[22,23] The coccygeus was examined 10 cm proximal to the introitus. All other pelvic floor muscle measurements were 5 cm from the introitus. Uterine tenderness was assessed vaginally at the posterior lower uterine segment. Approximately 2 kg of pressure was applied to each pelvic floor and uterine site and participants were asked to rate their level of pain from 0–10 (0=no pain, 10=worst imaginable pain).
2.5. Definition of Abdominal, Pelvic Floor, and Uterine Tenderness
Abdominal, pelvic floor and uterine tenderness were categorized as high and low tenderness based on the distribution of tenderness to determine cut-points. High abdominal tenderness was defined as reporting >1 abdominal area as tender. High uterine tenderness was defined as reporting uterine tenderness with a pain rating of >4 on the 0–10 pain scale (considered as moderate/severe pain[24–26]). Finally, high pelvic floor tenderness was defined as reporting >2 tender pelvic floor areas with a pain rating of >4 on the 0–10 pain scale for each area.
2.6. Statistical Analyses
Participants were eligible for inclusion in analyses if they had complete data from the physical exam. Of the 114 endometriosis and CPP patients enrolled into the study, 88 had complete physical exam data. In these exploratory analyses, we used Chi-square and Fisher’s Exact tests, where appropriate, to quantify the associations between high tenderness and the following categorical variables: endometriosis/CPP status (EndoØPain, Endo+Pain, CPPØEndo), endometriosis stage (I/II, III/IV), number of abdominal surgeries (1, 2, ≥3), dysmenorrhea (none/mild, moderate/severe), dysuria (none/mild, moderate/severe), dyschezia (none/mild, moderate/severe), dyspareunia (deep pain: none/mild, moderate/severe), dyspareunia (pain with entry: none/mild, moderate/severe), and McGill Present Pain Intensity (no/mild pain, discomforting/distressing pain, horrible/excruciating pain). We used T-tests and Wilcoxon Rank Sum tests, where appropriate to assess the associations between high tenderness on physical exam and ‘faint’, ‘mild’, and ‘slightly intense’ pressure pain levels (kgf/cm2), duration of pelvic pain (years), and the EHP-30 scales (Pain, Control and helplessness, Emotion, Social, Self-image). Participants missing any of the variables above were excluded in the separate individual analyses.
All analyses were performed using SAS 9.4 (Cary, NC). All p-values were 2-sided and considered statistically significant if less than 0.05.
3. Results
3.1. Study Population Characteristics
Among the 88 study participants, the majority were White, nulliparous, current hormone users, and reported severe dysmenorrhea (Table 1). The average age was 31.3 years and approximately half of the participants reported at least 4.5 years of pelvic pain. Among all participants, 27 were classified as EndoØPain, 46 as Endo+Pain and 15 as CPPØEndo. Approximately 42% of participants reported >1 abdominal tender area (high abdominal tenderness; Figure 1), with the majority experiencing tenderness located in the lower quadrants (Supplemental Table 1). Additionally, 50% of participants reported >2 moderate/severe pelvic floor tender areas (high pelvic floor tenderness; Figure 1), with the median pelvic floor pain scores ranging from 4.0–6.0 (Supplemental Table 1). For uterine tenderness, 58% reported moderate/severe uterine tenderness (high uterine tenderness). Overall, 32% of participants reported high tenderness for each of the three areas (abdominal, pelvic floor, uterine; Supplemental Figure 1).
Table 1.
| N | Mean (SD) | |
|---|---|---|
| Age (years) | 88 | 31.3 (8.5) |
| Body mass index (kg/m2) | 87 | 25.9 (5.4) |
| N | Median (IQR) | |
| Pain duration (years) | 86 | 4.5 (1.5–9) |
| N | % | |
| Race | ||
| White | 77 | 88.5 |
| Non-white | 10 | 11.5 |
| Current hormone use | ||
| No | 42 | 48.3 |
| Yes | 45 | 51.7 |
| Current narcotic use | ||
| No | 72 | 81.8 |
| Yes | 16 | 18.2 |
| Current antidepressant use | ||
| No | 76 | 86.4 |
| Yes | 12 | 13.6 |
| Current physical therapy for pelvic pain | ||
| No | 84 | 95.5 |
| Yes | 3 | 4.5 |
| Parity | ||
| Nulliparous | 55 | 62.5 |
| Parous | 33 | 37.5 |
| Endometriosis/CPP status3 | ||
| Endo∅Pain | 27 | 30.7 |
| Endo+Pain | 46 | 52.3 |
| CPP∅Endo | 15 | 17.1 |
| Dysmenorrhea | ||
| None/mild | 16 | 18.6 |
| Moderate | 13 | 15.1 |
| Severe | 57 | 66.3 |
SD=standard deviation, IQR=interquartile range
Sample size does not always equal to 88 due to missing data – 2 missing for pain duration and dysmenorrhea, 1 missing for body mass index, race, and current hormone use
EndoØPain=endometriosis participants without dysmenorrhea or chronic pelvic pain; Endo+Pain=endometriosis participants with dysmenorrhea or chronic pelvic pain; CPPØEndo=chronic pelvic pain participants without endometriosis
Figure 1: Number of abdominal and moderate/severe pelvic floor tender areas among endometriosis and chronic pelvic pain patients.
Blue = abdominal; Orange = pelvic floor; Abdominal tenderness assessed at right/left upper abdomen, right/left lower abdomen, suprapubic area, and umbilical area. Pelvic floor tenderness assessed at right/left pubococcygeus, right/left iliococcygeus, and right/left coccygeus muscles. Moderate/severe pelvic floor tenderness based on pain rating of ≥4 on a 0–10 pain scale at a specific tender area.
3.2. Nonpelvic Pressure Pain Sensitivity and Endometriosis/CPP Characteristics
High pelvic floor tenderness was associated with lower pressure intensities needed to elicit ‘faint’ and ‘mild’ pressure pain at the non-dominant thumbnail compared to participants with low pelvic floor tenderness (p=0.006 and 0.03, respectively; Table 2). High pelvic floor tenderness was also associated with lower pressure intensities needed to elicit ‘slightly intense’ at the non-dominant thumbnail; however, the association was not statistically significant (p=0.12). No significant differences for pressure pain sensitivity were observed for abdominal and uterine tenderness (p>0.10). Those with high tenderness in each of the three regions (abdominal wall, pelvic floor, uterus) were significantly more likely to have Endo+Pain or CPPØEndo compared to EndoØPain. Additionally, participants with high abdominal and uterine tenderness were more likely to have reported three or more previous abdominal surgeries compared to those with low tenderness (p=0.06 and 0.09, respectively).
Table 2.
Associations of pressure pain sensitivity and endometriosis/CPP characteristics with the number of tender areas in the pelvic floor, abdomen, and uterus1
| Pelvic floor tender areas2 | Abdominal tender areas3 | Uterine tenderness4 | |||||||
|---|---|---|---|---|---|---|---|---|---|
| Low Tenderness (N=44) | High Tenderness (N=44) | p-value5 | Low Tenderness (N=51) | High Tenderness (N=37) | p-value5 | Low Tenderness (N=37) | High Tenderness (N=51) | p-value5 | |
| Pressure intensity (kgf/cm2) at non-dominant thumbnail needed to elicit | |||||||||
| ‘faint’ pain | 1.06 (0.25–3.00) | 0.50 (0.25–3.25) | 0.006 | 0.88 (0.25–3.00) | 0.63 (0.25–3.25) | 0.18 | 1.00 (0.25–3.00) | 0.63 (0.25–3.25) | 0.11 |
| ‘mild’ pain | 2.63 (0.75–6.00) | 2.00 (0.63–4.88) | 0.03 | 2.25 (0.63–6.00) | 2.50 (0.75–4.88) | 0.60 | 2.63 (0.75–6.00) | 2.25 (0.63–5.75) | 0.33 |
| ‘slightly intense’ pain | 4.13 (1.13–10.0) | 3.31 (1.38–7.63) | 0.12 | 4.13 (1.13–10.0) | 3.44 (1.13–7.63) | 0.25 | 4.25 (1.13–7.65) | 3.44 (1.38–10.0) | 0.30 |
| Endometriosis and CPP status | |||||||||
| Endo∅Pain | 21 (47.7) | 6 (13.6) | 0.002 | 24 (47.1) | 3 (8.1) | <0.001 | 20 (54.1) | 7 (13.7) | <0.001 |
| Endo+Pain | 17 (38.6) | 29 (65.9) | 23 (45.1) | 23 (62.2) | 16 (43.2) | 30 (58.8) | |||
| CPP∅Endo | 6 (13.6) | 9 (20.4) | 4 (7.8) | 11 (29.7) | 1 (2.7) | 14 (27.5) | |||
| Endometriosis stage6 | |||||||||
| Stage I/II | 13 (34.2) | 27 (81.8) | <0.001 | 20 (44.4) | 20 (76.9) | 0.008 | 11 (31.4) | 29 (80.6) | <0.001 |
| Stage III/IV | 25 (65.8) | 6 (18.2) | 25 (55.6) | 6 (23.1) | 24 (68.6) | 7 (19.4) | |||
| Number of abdominal surgeries (laparoscopy or laparotomy) | |||||||||
| One | 20 (47.6) | 22 (51.2) | 0.94 | 29 (60.4) | 13 (35.1) | 0.06 | 22 (62.9) | 20 (40.0) | 0.09 |
| Two | 12 (28.6) | 11 (25.6) | 11 (22.9) | 12 (32.4) | 8 (22.8) | 15 (30.0) | |||
| Three or more | 10 (23.8) | 10 (23.3) | 8 (16.7) | 12 (32.4) | 5 (14.3) | 15 (30.0) | |||
Data are given as median (range) for continuous variables and sample size (percentage) for categorical variables.
Pelvic floor tender areas assessed at right/left pubococcygeus, right/left iliococcygeus, and right/left coccygeus. Each area reported as tender was palpated with 2kg of pressure and a 0–10 pain rating was obtained. High tenderness defined as >2 areas with pain rating of ≥4 on 0–10 scale (moderate/severe pain).
Abdominal tender areas assessed at right/left upper and right/left lower abdominal, suprapubic and umbilical areas. High tenderness defined as >1 tender area reported as tender.
Uterine tenderness assessed at posterior lower uterine segment with single digit vaginal exam. Participants with uterine tenderness had 2kg of pressure applied to the area and reported a 0–10 pain rating. High tenderness was defined as uterine tenderness with a pain rating of ≥4 on 0–10 scale (moderate/severe pain).
Two-sided probability values from Chi-square or Fisher’s exact test for categorical variables and from Wilcoxon Rank Sum for continuous variables
Among endometriosis cases with information on stage (n=70)
Three participants were missing information on number of laparoscopic surgeries/laparotomies
3.3. Pain Symptoms and Quality of Life
Women with high pelvic floor, uterine and abdominal wall tenderness reported higher (worse) EHP scores for each of the eight sub-scales of the EHP-30 compared to women with low tenderness (Table 3). Women with high uterine tenderness were more likely to report longer duration of pain compared to women with low tenderness (5.0 vs. 2.0 years; p=0.04) and there was a suggestion of longer pain duration among women with high abdominal tenderness compared to low (5.0 vs. 3.5 years; p=0.09). For each of the regions (abdominal wall, pelvic floor and uterus), women with high tenderness were also significantly more likely to report moderate/severe dysmenorrhea, and moderate/severe dyspareunia (both deep pain and pain with entry; p<0.0001). Pelvic floor, uterine and abdominal tenderness were not associated with severity of dysuria and dyschezia except that high uterine tenderness was associated with moderate/severe dyschezia (p=0.01). Finally, high tenderness for each of the regions was significantly associated with worse ratings on the McGill Present Pain Intensity scale with approximately 18% of high pelvic floor tenderness participants (vs. 7% low tenderness), 25% of high abdominal tenderness (vs. 4% low tenderness), and 23% of high uterine tenderness (vs. 0% low tenderness) reporting horrible/excruciating pain.
Table 3.
Associations of pain symptoms and Endometriosis Health Profile-30 scales with the number of tender areas in the pelvic floor, abdomen, and uterus1,2
| Pelvic floor tender areas3 | Abdominal tender areas4 | Uterine tenderness5 | |||||||
|---|---|---|---|---|---|---|---|---|---|
| Low Tenderness (N=44) | High Tenderness (N=44) | p-value6 | Low Tenderness (N=51) | High Tenderness (N=37) | p-value6 | Low Tenderness (N=37) | High Tenderness (N=51) | p-value6 | |
| Duration of pain (years) | 4.50 (0–29) | 4.50 (0–20) | 0.71 | 3.50 (0–26) | 5.00 (0.83–29.0) | 0.09 | 2.00 (0–29) | 5.00 (0.83–23) | 0.04 |
| Endometriosis Health Profile-30 | |||||||||
| Pain | 9.09 (0–56.8) | 38.6 (0–75.0) | <0.001 | 13.6 (0–68.2) | 38.6 (0–75.0) | <0.001 | 4.55 (0–68.2) | 40.9 (0–75.0) | <0.001 |
| Control and helplessness | 4.17 (0–91.7) | 50.0 (0–95.8) | <0.001 | 16.7 (0–91.7) | 50.0 (0–95.8) | <0.001 | 0 (0–83.3) | 50.0 (0–95.8) | <0.001 |
| Emotion | 4.17 (0–58.3) | 33.3 (0–79.2) | <0.001 | 8.33 (0–62.5) | 29.2 (0–79.2) | 0.004 | 0 (0–62.5) | 33.3 (0–79.2) | <0.001 |
| Social | 6.25 (0–81.3) | 37.5 (0–100) | 0.001 | 6.25 (0–75.0) | 37.5 (0–100) | 0.002 | 6.25 (0–68.8) | 37.5 (0–100) | <0.001 |
| Self-image | 8.33 (0–75) | 41.7 (0–83.3) | <0.001 | 16.7 (0–75.0) | 50.0 (0–83.3) | <0.001 | 0 (0–58.3) | 41.7 (0–83.3) | <0.001 |
| Dysmenorrhea | |||||||||
| None/mild | 15 (35.7) | 1 (2.3) | <0.001 | 16 (32.0) | 0 (0.0) | <0.001 | 14 (37.8) | 2 (4.1) | <0.001 |
| Moderate/Severe | 27 (64.3) | 43 (97.7) | 34 (68.0) | 36 (100) | 23 (62.2) | 47 (95.9) | |||
| Dysuria | |||||||||
| None/mild | 39 (92.9) | 37 (84.1) | 0.31 | 44 (88.0) | 32 (88.9) | 0.99 | 34 (94.4) | 42 (84.0) | 0.18 |
| Moderate/Severe | 3 (7.1) | 7 (15.9) | 6 (12.0) | 4 (11.1) | 2 (5.6) | 8 (16.0) | |||
| Dyschezia | |||||||||
| None/mild | 30 (71.4) | 24 (54.5) | 0.11 | 33 (66.0) | 21 (58.3) | 0.47 | 28 (77.8) | 26 (52.0) | 0.01 |
| Moderate/Severe | 12 (28.6) | 20 (45.5) | 17 (34.0) | 15 (41.7) | 8 (22.2) | 24 (48.0) | |||
| Dyspareunia (deep pain) | |||||||||
| None/mild | 26 (63.4) | 9 (21.4) | <0.001 | 29 (59.2) | 6 (17.6) | <0.001 | 24 (68.6) | 11 (22.9) | <0.001 |
| Moderate/Severe | 15 (36.6) | 33 (78.6) | 20 (40.8) | 28 (82.4) | 11 (31.4) | 37 (77.1) | |||
| Dyspareunia (pain with entry) | |||||||||
| None/mild | 35 (85.4) | 23 (54.8) | 0.002 | 40 (83.3) | 18 (51.4) | 0.002 | 32 (91.4) | 26 (54.2) | <0.001 |
| Moderate/Severe | 6 (14.6) | 19 (45.2) | 8 (16.7) | 17 (48.6) | 3 (8.6) | 22 (45.8) | |||
| McGill Present Pain Intensity | |||||||||
| No/mild pain | 31 (73.8) | 12 (27.3) | <0.001 | 36 (72.0) | 7 (19.4) | <0.001 | 30 (81.1) | 13 (26.5) | <0.001 |
| Discomforting/distressing pain | 8 (19.1) | 24 (54.5) | 12 (24.0) | 20 (55.6) | 7 (18.9) | 25 (51.0) | |||
| Horrible/excruciating pain | 3 (7.1) | 8 (18.2) | 2 (4.0) | 9 (25.0) | 0 (0.0) | 11 (22.5) | |||
Data are given as median (range) for continuous variables and sample size (percentage) for categorical variables.
Sample size is 86 for pain duration, dysmenorrhea, dysuria, dyschezia, and McGill present pain intensity; sample size is 83 for dyspareunia (deep pain) and dyspareunia (pain with entry); sample size is 80 for Endometriosis Health Profile-30 scales
Pelvic floor tender areas assessed at right/left pubococcygeus, right/left iliococcygeus, and right/left coccygeus. Each area reported as tender was palpated with 2kg of pressure and a 0–10 pain rating was obtained. High tenderness defined as >2 areas with pain rating of ≥4 on 0–10 scale (moderate/severe pain).
Abdominal tender areas assessed at right/left upper and right/left lower abdominal, suprapubic and umbilical areas. High tenderness defined as >1 tender area reported as tender.
Uterine tenderness assessed at posterior lower uterine segment with single digit vaginal exam. Participants with uterine tenderness had 2kg of pressure applied to the area and reported a 0–10 pain rating. High tenderness was defined as uterine tenderness with a pain rating of ≥4 on 0–10 scale (moderate/severe pain).
Two-sided probability values from Chi-square or Fisher’s exact test for categorical variables and from Wilcoxon Rank Sum for continuous variables
4. Discussion
The high prevalence of both endometriosis and CPP among women of reproductive age necessitates an improved understanding of the mechanisms contributing to both conditions, especially when they co-occur, in order to improve early detection for risk of CPP and to inform treatment decisions. The results of the present study indicate that women with CPP, both with and without endometriosis, had high pelvic floor, abdominal and uterine tenderness when compared to women with endometriosis without pain. Additionally, higher pelvic floor tenderness was associated with higher pressure pain sensitivities on the non-dominant thumbnail. These findings suggest that high pelvic floor tenderness is associated with CNS pain amplification in at least some women with CPP. Tenderness in each of the three areas was also related to worse pain intensity, including dysmenorrhea and dyspareunia, as well as overall worse emotional functioning. Collectively, these results offer potentially important insight into the mechanisms of pain in women with CPP or endometriosis, which in turn could impact personalized treatment options.
Our results are consistent with other findings of high pelvic floor and abdominal tenderness among CPP patients and of higher pressure pain sensitivities in women with endometriosis with pain or CPP.[14,22,27,28] Similar to our results, Montenegro et al (2010) observed a prevalence of 58.3% for pelvic floor tenderness among CPP patients with higher pelvic floor tenderness associated with higher Beck Depression Index scores, dyspareunia, and constipation.[27] Additionally, previous research has shown that endometriosis patients have significantly lower PPTs at an abdominal wall tender point compared to healthy controls while women with CPP had lower PPTs at pelvic floor muscles compared to pain-free women.[12,14] However, this study is the first to examine how nonpelvic pain sensitivities relate to external and internal abdominal, uterine, and pelvic floor tender areas and to examine tenderness in all three areas with endometriosis pain status. More research is needed on larger samples to confirm our results and to explore other salient QST variables (e.g. temporal summation and conditioned pain modulation) or functional neuroimaging in order to further elucidate the relationship between sensory functioning and endometriosis pain/CPP. Additionally, it would be important for future studies to explore how abdominal, pelvic floor, and uterine tender areas may be a potential marker for future development of CPP.
Treatment for endometriosis has traditionally focused on the lesions; however, endometriosis is a heterogeneous disease with multiple pain mechanisms that are not limited to only the lesions. Currently, there are no valid assessments to distinguish patients with different mechanisms of pain. The results of this study suggest that testing for pelvic floor tenderness as a part of a routine pelvic examination may be one component that is useful in identifying women with heightened overall pain sensitivity, and should be examined further in future research. Currently, pelvic examinations vary widely with many internal pelvic exams focusing on nodularity or masses, but not necessarily trying to identify focal tenderness of distinct pelvic areas,[29,30] suggesting there is a need to develop and implement standardized assessments for pelvic tenderness during examinations.[31,32] Further, co-existing pelvic floor tenderness and CNS pain amplification may explain why some women with pelvic floor tenderness do not respond solely to peripherally directed treatments such as pelvic floor physical therapy. These women may be refractory to standard treatments such as NSAIDS and repeated surgeries that largely target the peripheral nervous system and neglect the role of the CNS in the maintenance and exacerbation of pain. Rather this population may benefit from an interdisciplinary pain treatment approach, such as integrated behavioral therapy, physical therapy, and/or medications that target the nervous system (e.g., anti-convulsant; tricyclic anti-depressants).
The assessment of pelvic tender areas was not based on validated assessment tools; however, the procedures were performed by a single clinician blinded to patient clinical status, standardized across all participants allowing for consistency throughout the study, and adapted from a pelvic exam tenderness protocol previously published.[22,23] Further, the sample of this study was fairly small with a mostly White population and while we had specific hypotheses about pressure pain thresholds and tenderness, the remaining analyses should be considered hypothesis generating. Future studies should include larger, more diverse populations. Finally, the definition of high and low tenderness was not based on a previously validated method, and future studies should explore additional cut-points in a bigger sample. A major strength of this study was the detailed information, operative reports and self-report pain symptoms, used to classify the endometriosis and CPP participants resulting in minimal misclassification. Additional strengths included the utilization of a researcher blinded to all study data and a standard protocol for the pressure pain sensitivity measurements.
5. Conclusions
Our findings that higher pelvic floor tenderness is associated with higher pressure pain sensitivity may explain why some women with pelvic tenderness do not respond solely to peripherally directed treatments as this pelvic tenderness may be a marker or consequence of concurrent CNS pain amplification in this subset of women. Future research should investigate whether comprehensive assessment of abdominal and pelvic tenderness may help to define a clinical phenotype that may predict differential treatment outcomes and even provide a step towards the use of more objective measures for individually tailored patient-oriented interventions.
Supplementary Material
Highlights.
About half of participants had high pelvic floor, abdominal, and uterine tenderness
Endometriosis Health Profile-30 scores lower for those with high tenderness
Pressure intensity levels were lower for those with high vs. low pelvic floor tenderness
High pelvic floor tenderness may be a marker of heightened pain sensitivity
Funding:
Supported in part by the National Institutes of Health (NIH) K12HD001438, NIH UL1RR024986, and the Bayer Droegemueller Award in Clinical Research. C.B.S. is funded by a K23 Award from NIH (GM123372), a grant from the Boston Center for Endometriosis, Marriott Foundation Investigator Award, and a grant from the Department of Defense (W81XWH1910560). S.A. is funded by NIH-DHHS-US-16-PAF06270 (R01 HD088712-05). A.L.S. and S.A.M. are funded by the Marriott Family Foundations and by the National Institutes of Health (NICHD R21HD096358-02). All funding sources had no role in study design, collection, analysis and interpretation of the data.
Declarations of Interest:
S.A. has served as a consultant for Abbvie, Bayer, Myovant Sciences and Merck, and receives royalties as an author for UpToDate. D.J.C. has served as a consultant for Pfizer, Lilly, Tonix, Aptinyx, Samumed, Zynerba, and has received research funding from Aptinyx. S.E.H. has served as a consultant for Aptinyx, and has received research funding from Arbor Medical Innovations and Aptinyx. S.A.M. has served as an advisory board member for Abbvie and Roche. A.L.S., E.M., and C.B.S. report no conflict of interest.
Abbreviations
- BMI
Body Mass Index
- CNS
Central nervous system
- CPP
Chronic pelvic pain
- EHP
Endometriosis Health Profile-30
- EndoØPain
Endometriosis with ≤4 days of moderate to severe pelvic pain per month
- Endo+Pain
Endometriosis with >4 days of moderate to severe pelvic pain per month
- CPPØEndo
Chronic pelvic pain without endometriosis
- GBS
Gracely Box Scale
- QST
Quantitative Sensory Testing
- PPT
Pressure pain threshold
Footnotes
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