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Cotton-tipped applicator test: validity and reliability in chronic pelvic pain

  • Maryam Nasr-Esfahani
    Correspondence
    Reprints: Maryam Nasr-Esfahani, MD, Department of Obstetrics and Gynecology, Foothills Medical Center, University of Calgary, 4th Floor N. Tower, Room 428, 1403 29 St. N.W., Calgary, Alberta T2N 2T9 Canada
    Affiliations
    Department of Obstetrics and Gynecology, Foothills Medical Center, University of Calgary, Calgary, Alberta, Canada
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  • John Jarrell
    Affiliations
    Department of Obstetrics and Gynecology, Foothills Medical Center, University of Calgary, Calgary, Alberta, Canada
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Published:November 19, 2012DOI:https://doi.org/10.1016/j.ajog.2012.11.005

      Objective

      We sought to assess the concurrent validity and interrater reliability of the cotton-tipped applicator (CTA) test as a screening tool for diagnosis of cutaneous allodynia in patients with viscerally related chronic pelvic pain (CPP).

      Study Design

      We performed a prospective cohort comparative observational study of referred patients to a gynecology clinic with CPP. A total of 22 females with CPP were compared to 23 pain-free controls and 12 cyclic pain patients. Participants were evaluated by 2 clinicians. The CTA test was performed to detect the appearance of pain in dermatomes of T10-L1.

      Results

      Interrater reliability resulted in 98% agreement for the 3 study groups. CTA test showed 73% sensitivity and 100% specificity for differentiating patients with CPP from pain-free patients.

      Conclusion

      The CTA test had excellent interrater reliability and concurrent validity for diagnosis of cutaneous allodynia in CPP patients with visceral diseases versus controls.

      Key words

      Chronic pelvic pain (CPP) causes disability and distress, significantly compromises quality of life, and affects health care costs.
      • Dalpiaz O.
      • Kerschbaumer A.
      • Mitterberger M.
      • Pinggera G.
      • Bartsch G.
      • Strasser H.
      Chronic pelvic pain in women: still a challenge.
      The American Congress of Obstetricians and Gynecologists has estimated that 15-20% of women in the age group 18-50 years have experienced pain of >1 year's duration and 4% continue to have ongoing persistent pain.
      American College of Obstetricians and Gynecologists
      ACOG Committee on Practice Bulletins–Gynecology ACOG practice bulletin no 51: chronic pelvic pain.
      The Society of Obstetricians and Gynecologists of Canada defines CPP as a pain lasting for ≥6 months, with incomplete relief despite treatment and significantly impaired function at home/work.
      • Jarrell J.F.
      • Vilos G.A.
      • Allaire C.
      • et al.
      Consensus guidelines for the management of chronic pelvic pain.
      CPP is a multicausal disease. While a multidisciplinary approach to management of these patients often proves to be effective, it still does not explain why some women continue to experience daily pain that is irresponsive to large doses of pain medications.
      • Baranowski A.P.
      Chronic pelvic pain.
      • Butrick C.W.
      Chronic pelvic pain: how many surgeries are enough?.
      The concept of the central sensitization may help to explain this medical problem.
      Central sensitization seems to be a common feature of chronic pain conditions. The concept of neuroplasticity explains the changes in the function of the central nervous system, particularly at the dorsal root ganglion.
      • Vecchiet L.
      • Vecchiet J.
      • Giamberardino M.A.
      Referred muscle pain: clinical and pathophysiologic aspects.
      The stimuli for the changes are multifactorial. Severe or prolonged visceral pain from organs in the pelvis appears to be one of the significant contributing factors. Visceral pain is typically localized by the brain's sensory cortex by visceral afferents to the respective spinal cord level.
      • Schorge J.O.
      • Williams J.W.
      Williams gynecology.
      Visceral afferents follow a segmental distribution. Visceral afferent fibers are poorly myelinated and the action potentials may easily spread from them to impact adjacent somatic nerves. As a result, visceral pain may at times be referred to dermatomes that correspond to the impacted somatic nerve fibers.
      • Giamberardino M.A.
      Referred muscle pain/hyperalgesia and central sensitization.
      In addition, both peripheral somatic and visceral nerves often synapse in the spinal cord at the same dorsal horn neurons. These neurons, in turn, relay sensory information to the brain. The cortex recognizes the signal as coming from the same dermatomes regardless of its visceral or somatic nerve origin. If noxious stimuli such as inflammatory process following endometriosis or pelvic inflammatory diseases continue for a prolonged period of time, neurons within spinal cord display increased excitability. This is termed “central sensitization.” In the case of the pelvis, it is associated with increased efferent activity that results in aberrant activity in pelvic organs. This persistent central hyperexcitability might cause an increase in perception of pain in visceral organs. Referred pain tends to be localized in areas corresponding to the dermatome and myotome that are supplied by the affected viscus, or remote from the inciting stimulus in an area supplied by the same neural segment as the injured organ. Creation of pain from an innocuous stimulus in the related cutaneous areas is referred to as cutaneous allodynia.
      Viscerosomatic pain referral has been evaluated by pain threshold measures and abdominal wall thermography tests. Pain threshold measure tests have been validated with the identification of chronic pain states.
      • KuKanich B.
      • Lascelles B.D.
      • Papich M.G.
      Use of a von Frey device for evaluation of pharmacokinetics and pharmacodynamics of morphine after intravenous administration as an infusion or multiple doses in dogs.
      • Dong H.
      • Sun H.
      • Magal E.
      • et al.
      Inflammatory pain in the rabbit: a new, efficient method for measuring mechanical hyperalgesia in the hind paw.
      • Giamberardino M.A.
      Women and visceral pain: are the reproductive organs the main protagonists? Mini-review at the occasion of the “European week against pain in women 2007”..
      Current methods for identifying patients with pain hypersensitivity are sufficiently complex to limit their widespread application in clinical settings.
      • Nixdorf D.R.
      • Hemmaty A.
      • Look J.O.
      • Schiffman E.L.
      • John M.T.
      Electric toothbrush application is a reliable and valid test for differentiating temporomandibular disorders pain patients from controls.
      The cotton-tipped applicator (CTA) test has been introduced to identify this group of patients.
      • Jarrell J.
      Demonstration of cutaneous allodynia in association with chronic pelvic pain.
      In an exploratory evaluation of the ability of 3 bedside tests in discriminating visceral disease from nonvisceral disease among women with CPP, the CTA test for cutaneous allodynia appeared to have the greatest likelihood of predicting preexisting or ongoing visceral disease.
      • Jarrell J.
      • Giamberardino M.A.
      • Robert M.
      • Nasr-Esfahani M.
      Bedside testing for chronic pelvic pain: discriminating visceral from somatic pain.
      The aim of the present study was to assess the test reliability and validity as a screening method by testing the presence of cutaneous allodynia among women with or without CPP. We hypothesized that this test was reliable, feasible, and valid for assessing cutaneous allodynia.

      Materials and Methods

      This research was carried out as a prospective cohort comparative observational trial. Subjects were recruited from referred patients to Calgary Chronic Pain Clinic and Foothills Medical Center from 2010 through 2011. The date of entry was the date of approval of the ethics application at the University of Calgary. Subjects were invited to participate in the study by a nurse practitioner or a researcher during a clinical consultation for the management of chronic pain. The presence of pelvic visceral disease (eg, endometriosis and adenomyosis) as a possible cause of CPP was determined based on a documented operative record from the health records of the Calgary Health Region of Alberta Health Services. Potential participants were given an explanation of the study and the opportunity to ask questions. Five women declined to participate due to time constraints, severity of their pain, or no specific reasons. After obtaining written informed consent, the participants' demographic information and medical history were reviewed. Subjects were then allocated into 3 groups based on their description of presence of pain:
      • 22 women with chronic continuous pelvic pain of ≥6 months' duration, not controlled with standard treatment.
      • 12 women with cyclic pelvic pain of ≥6 months' duration, not controlled with standard treatment (sample of convenience).
      • 23 women who had no pelvic pain and were referred to Foothills Medical Center for other gynecological reasons.
      The standard treatment for pelvic pain was defined as having at least 1 pelvic surgery including a diagnostic or operative laparoscopic surgery, abdominal or vaginal hysterectomies, hormone therapy such as continuous oral contraceptive pills, progesterone therapy and Mirena intrauterine device, mild analgesics and narcotics.
      Exclusion criteria for participation in the study included pregnant/breast-feeding women; women with major medical illnesses such as lupus, diabetes mellitus, or neurologic diseases; and those who did not provide written consent.

      CTA test

      Two trained clinicians performed the CTA test to determine the presence or absence of CA. Using a table of random numbers, the order of testing was determined. Testing was done during the 5th-10th days of the participant menstrual cycle if menstruating to avoid possible variation in pain sensitivity across different stages of menstrual cycle.

      Abdominal test

      A CTA was gently passed down from the midclavicular line under ribs on each side of the abdomen to the supra pubic area. It was then directed across the abdomen in the region of the T10-L1 dermatomes. Subjects were instructed to report the appearance of pain by giving signals to clinician. If the sensation suddenly changed and produced a sharp painful sensation despite gentle pressure, the test was considered positive. The participants were asked to score the severity of pain based on visual analog scale. The entire area was marked with a washable marker and a photograph was taken. After the area was washed, the process was repeated by the second observer. The time frame for performing the evaluations by the 2 raters was between 5-15 minutes. For a video presentation of the abdominal test, refer to “Demonstration of Cutaneous Allodynia in Association with Chronic Pelvic Pain” by Jarrell.”
      • Jarrell J.
      Demonstration of cutaneous allodynia in association with chronic pelvic pain.
      The primary outcome was measured based on a dichotomous “yes/no” response.

      Test validity

      Concurrent validity assessment was based on observing the rates of cutaneous allodynia among those with continuous pain due to pelvic visceral disease and those with no pain. For further assessment of validity the rates of cutaneous allodynia between pain subjects and those with cyclic pain was assessed.
      • Fletcher R.H.
      • Fletcher S.W.
      Clinical epidemiology: the essentials.
      • Miller L.A.
      • McIntire S.A.
      • Lovler R.L.
      Foundations of psychological testing: a practical approach.

      Test reliability

      Interrater reliability was measured based on the raters' agreement on the presence or absence of cutaneous allodynia in each of the 3 groups.
      • Fletcher R.H.
      • Fletcher S.W.
      Clinical epidemiology: the essentials.
      • Miller L.A.
      • McIntire S.A.
      • Lovler R.L.
      Foundations of psychological testing: a practical approach.
      Based on preliminary data and clinical experience, it was expected that 80% of women with continuous pain would have a positive CTA test and that no one without pain would show a positive CTA test. Assuming a significance level of .05, a sample size of 20 patients in each group would give >95% power to detect such a difference. Descriptive statistics were used to summarize participant characteristics. The Mann-Whitney U test was used to compare duration of pain and pain intensity between the continuous and cyclic pain groups.
      To assess concurrent validity, the χ2 test was used to compare the CTA test's ability to distinguish between women with continuous pelvic pain vs those with no pelvic pain, and women with continuous pain vs cyclic pain. Sensitivity and specificity of the CTA test was reported with the corresponding exact 95% confidence intervals. Interrater reliability was measured using the proportion of agreement and McNemar test. Software (SAS 9.2; SAS Institute Inc, Cary, NC) was used for analysis.

      Results

      Of the 64 women enrolled in the study, 7 women were excluded from the continuous pain group due to causes other than visceral disease such as motor vehicle accident, trauma, or complications of their surgery. A total of 57 women were included in the analysis.
      Population demographics are listed in Table 1. The mean age of participants, gravidity, and parity in the 3 study groups were similar. The median duration of pain was comparable in the continuous group and the cyclic pain group (6 vs 5 years). Patients in the continuous pain group had higher baseline pain intensity, all >5 on a visual analog scale of 0-10.
      TABLE 1Participant characteristics
      CharacteristicContinuous pain (n = 22)Cyclic pain (n = 12)No pain (n = 23)
      Mean age, y (SD)35 (10)37 (8)39 (8)
       G0, P011 (50%)8 (67%)8 (35%)
       G>0, P01 (5%)0 (0%)4 (17%)
       G>0, P>010 (45%)4 (33%)11 (48%)
      Median duration of pain,
      Excludes n = 1 unknown in cyclic pain group.
      y
      6 (IQR 10)5 (IQR 8)N/A
      Range, 2–17Range, 1–30
      Median pain intensity on VAS6 (IQR 1)5 (IQR 2)N/A
      Range, 5–8Range, 4–10
      G, gravidity; IQR, interquartile range; N/A, not applicable; P, parity; VAS, visual analog scale.
      Nasr-Esfahani. The validity and reliability of Q-tip in visceral chronic pelvic pain. Am J Obstet Gynecol 2013.
      a Excludes n = 1 unknown in cyclic pain group.

      Assessment of validity

      The CTA test reached excellent discrimination of continuous CPP cases from pain-free controls (P value < .001), with 73% sensitivity and 100% specificity (TABLE 2, TABLE 3). It also showed moderate discrimination of continuous CPP cases from cyclic pain controls (P value < .001), providing further evidence for concurrent validity.
      TABLE 2Cotton-tipped applicator test outcomes
      Primary outcomeContinuous pain (n = 22)No pain (n = 23)χ2 test P value
      Positive CTA test16 (73%)0 (0%)< .001
      Negative CTA test6 (27%)23 (100%)
      Secondary outcomesContinuous pain (n = 22)Cyclic pain (n = 12)
      Positive CTA test16 (73%)1 (8%)< .001
      Negative CTA test6 (27%)11 (92%)
      CTA, cotton-tipped applicator.
      Nasr-Esfahani. The validity and reliability of Q-tip in visceral chronic pelvic pain. Am J Obstet Gynecol 2013.
      TABLE 3Sensitivity and specificity of cotton-tipped applicator test in detecting continuous pain vs no pain (n = 45)
      VariablePercent95% confidence interval
      Sensitivity7350–89%
      Specificity10085–100%
      Nasr-Esfahani. The validity and reliability of Q-tip in visceral chronic pelvic pain. Am J Obstet Gynecol 2013.

      Assessment of reliability

      The CTA test showed 98% (95% confidence interval, 0.91–1.00) agreement between 2 raters with the McNemar test P value of .317 (Table 4). Only 1 participant in the continuous pain group tested positive by one clinician and negative by the second. The Figure depicts a few photographs of patients taken after each examiner performed the CTA test to highlight the degree of agreement between examiners.
      TABLE 4Interrater reliability of cotton-tipped applicator test (includes all 57 cases)
      VariableRater 2 positive CTARater 2 negative CTA
      Rater 1 positive CTA16 (28%)1 (2%)
      Rater 1 negative CTA0 (0%)40 (70%)
      Statistical result95% confidence interval
      McNemar test P value0.317N/A
      Interrater reliability98%91–100%
      CTA, cotton-tipped applicator; N/A, not applicable.
      Nasr-Esfahani. The validity and reliability of Q-tip in visceral chronic pelvic pain. Am J Obstet Gynecol 2013.
      Figure thumbnail gr1
      FIGUREA sample of the CTA test photographs
      Two photographs set side by side depict the same patient.
      CTA, cotton-tipped applicator.
      Nasr-Esfahani. The validity and reliability of Q-tip in visceral chronic pelvic pain. Am J Obstet Gynecol 2013.

      Comment

      Appropriate tests are invaluable to clinicians; they may be used to legitimize patients' concerns and reassure them about their prognosis. Unfortunately, many CPP patients interpret a physician's report of a normal test result as a statement that their anatomy is normal and their pain must be in their mind.
      • Levy B.S.
      Diagnostic studies.
      We used the CTA test as a screening method in patients with chronic pain to validate their concerns and to possibly avoid the expense and discomfort of repeating evaluations.
      An evaluation of 3 bedside tests concluded that the CTA test appears to have a greater likelihood of identifying cutaneous allodynia in patients with a visceral source of pain compared to somatic sources of pain.
      • Jarrell J.
      • Giamberardino M.A.
      • Robert M.
      • Nasr-Esfahani M.
      Bedside testing for chronic pelvic pain: discriminating visceral from somatic pain.
      Consistent with the current study, it noted that patients with a history of preexisting or concurrent visceral disease showed a higher rate of cutaneous allodynia. The value of the test when positive would appear to indicate the presence of a current or previous visceral disease. When negative, it can provide some reassurance that presence of pain may not be due to central sensitization and the central sensitization has not yet developed in response to an internal visceral disease.
      In addition, in the current study, 4 women with a hysterectomy and bilateral salpingo-oophorectomy for previous visceral disease had a negative test despite having a chronic pain state. Another woman in the continuous pain group had complete suppression of her menstruation for the last 3 years. This may indicate that the treatment of endometriosis with the induction of amenorrhea may be the first step in reversing the effects of neuroplasticity and helping these patients to combat the process of chronic pain state. This observation cannot be generalized due to limitations with the small number.
      Only 1 patient in the cyclic pain group showed a positive CTA test. She had documented endometriosis on her operative report and 10 years of severe dysmenorrhea. Her young age may predict that she may end up having chronic pain state if not treated aggressively to reverse the effects of endometriosis.
      This project evaluated an effective office procedure, a noninvasive method that requires no sedation and can be repeated as desired in follow-up evaluations. It can be easily undertaken at the bedside. It is not time-consuming and is well tolerated by patients. The device is inexpensive, small, and easy to use. The CTA test can provide clinicians with a useful practical approach and may have significant implications in the recognition of central sensitization.
      The strengths of the study are the consistency with our understanding of central sensitization
      • Giamberardino M.A.
      • Affaitati G.
      • Lerza R.
      • Lapenna D.
      • Costantini R.
      • Vecchiet L.
      Relationship between pain symptoms and referred sensory and trophic changes in patients with gallbladder pathology.
      and previous studies of cutaneous allodynia
      • Jarrell J.
      • Giamberardino M.A.
      • Robert M.
      • Nasr-Esfahani M.
      Bedside testing for chronic pelvic pain: discriminating visceral from somatic pain.
      as well as the significant findings related to validity and reliability. However, it should be noted that a high percent agreement does not always indicate that the raters are correct. In our study, since the sensitivity and specificity are high, it can be extrapolated that a high percent agreement infers that both raters are correct.
      The limitations of the study include the small number of cases. The clinicians were not blinded to the pain condition of patients, which could affect the results of the CTA test especially in the pain-free controls.
      Further studies of this simple test in the clinical environment appear warranted.

      Conclusion

      In summary, this study showed that the CTA test has excellent concurrent validity with significant specificity and sensitivity, and excellent interrater reliability in the detection of central sensitization and cutaneous allodynia in patients with continuous pain due to visceral disease.

      Acknowledgments

      The support of the Department of Obstetrics and Gynecology, University of Calgary; Dr Sue Ross; and Selphee Tang, data analyst, is appreciated.

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