Prediction of Persistent Post-Mastectomy Pain
| Status: | Recruiting |
|---|---|
| Conditions: | Chronic Pain, Chronic Pain |
| Therapuetic Areas: | Musculoskeletal |
| Healthy: | No |
| Age Range: | 18 - 80 |
| Updated: | 7/13/2017 |
| Start Date: | October 2014 |
| End Date: | October 2017 |
Chronic pain is devastating both to individuals and society. In an aging population, surgery
is an increasing cause of chronic pain, with rates of persistent post-operative pain ranging
from 10-65%.In particular, Persistent Post-Mastectomy Pain (PPMP) occurs in roughly one third
of women who have had mastectomy. The occurrence of PPMP does not seem to be strongly
determined by the type of surgery, chemotherapy, and radiation treatment, suggesting that
individual person-specific factors may play a more important role. In fact, recent studies
indicate that individual differences in pain sensitivity (psychophysics) are more closely
associated with PPMP than surgical/medical variables. Specifically, sensory testing revealed
that women who developed PPMP had lower pressure pain thresholds and greater temporal
summation of pain stimuli than women who did not develop this chronic pain condition.
Moreover, psychosocial factors such as anxiety, depression, catastrophizing, and somatization
were more prominent in women with PPMP. These preliminary, retrospective studies suggest that
individual psychophysical and psychosocial characteristics could be important risk factors
for PPMP. Accordingly, the aim of this study is to comprehensively and prospectively study
women having mastectomy surgery, to determine the relationship between pre-operative
psychophysical and psychosocial factors and the development of PPMP. Using these data, a
prediction model for PPMP will be developed, thus allowing a preoperative calculation of a
"PPMP risk score" for any patient facing mastectomy.
is an increasing cause of chronic pain, with rates of persistent post-operative pain ranging
from 10-65%.In particular, Persistent Post-Mastectomy Pain (PPMP) occurs in roughly one third
of women who have had mastectomy. The occurrence of PPMP does not seem to be strongly
determined by the type of surgery, chemotherapy, and radiation treatment, suggesting that
individual person-specific factors may play a more important role. In fact, recent studies
indicate that individual differences in pain sensitivity (psychophysics) are more closely
associated with PPMP than surgical/medical variables. Specifically, sensory testing revealed
that women who developed PPMP had lower pressure pain thresholds and greater temporal
summation of pain stimuli than women who did not develop this chronic pain condition.
Moreover, psychosocial factors such as anxiety, depression, catastrophizing, and somatization
were more prominent in women with PPMP. These preliminary, retrospective studies suggest that
individual psychophysical and psychosocial characteristics could be important risk factors
for PPMP. Accordingly, the aim of this study is to comprehensively and prospectively study
women having mastectomy surgery, to determine the relationship between pre-operative
psychophysical and psychosocial factors and the development of PPMP. Using these data, a
prediction model for PPMP will be developed, thus allowing a preoperative calculation of a
"PPMP risk score" for any patient facing mastectomy.
This study is a prospective observational study which phenotypes individuals' baseline pain,
psychosocial and psychophysical characteristics, then measures perioperative and long-term
changes to examine the relationship of psychophysical and psychosocial processing to
persistent post-mastectomy pain development .
Preoperative Psychophysical assessment:
Pressure pain testing methods: After giving informed consent, the PI or a fully trained
member of the research staff will administer a brief QST session. Pressure pain threshold and
tolerance will be assessed using a digital pressure algometer (Wagner FDX, Greenwich, CT,
USA) with a flat round transducer, probe area 0.785 cm2. Testing sites will be bilateral on
the dorsal aspect of the proximal forearm (extremity site) and over the trapezius muscle at
the upper back (truncal site). For pressure threshold determination, pressure is increased at
a steady rate of approximately 1 kg/second until subject indicates that the pressure is first
perceived as painful. Pressure pain tolerance will be determined by instructing patients to
indicate the pressure at which the pain was no longer tolerable. Two trials will be performed
at each site.
Temporal Summation testing methods: Mechanical pinprick pain will be assessed using
standardized weighted pinprick applicators similar to those described by Rolke et al99 of two
designated forces (256mN and 512mN) which result in a painful sensation in most
subjects.1-2,100 First, a single stimulation of the lower force pinprick will be applied to
the dorsal aspect of the index finger between the first and second interphalangeal joints of
the each hand while resting palm down on the armrest, and then rated by the subject on a
scale of 0-10. Next, after a break of at least 10 seconds, a train of 10 stimuli will be
applied at the same premarked spot, at a rate of 1 stimulation/second. The subject will rate
pain on a scale of 0-10 after the first, fifth and tenth stimulus, then rate any ongoing pain
15 and 30 seconds after cessation of the last stimulus. The same procedure will be repeated
using the higher force pinprick on the third finger of the each hand. Subjects will undergo
two trials at each force, with a break of at least one minute between trials.
Psychosocial Assessment: Preoperative demographic, medical, psychosocial and pain
questionnaires will be completed by the patient during their preoperative office visit.
Questionnaires assessing psychosocial factors are chosen based upon previous association with
PPMP, strong psychometric validation characteristics, and brevity. The Pain Catastrophizing
Scale (PCS), which has been validated in pain patients and controls, will be used to measure
catastrophic thinking associated with pain. Depressive symptoms, anxiety and sleep
disturbance will be assessed using short-form instruments from the NIH roadmap initiative,
Patient Reported Outcome Measurement Information System (PROMIS), which have been extensively
validated in studies comparing results with established scales, and have been calibrated on
over 20,000 persons. The Brief Symptom Index 18-Somatization Scale, also previously validated
in chronic pain patients,107 will be used to measure somatization.
Pain assessment: The primary pain outcome measure will be Pain Burden Index as measured by
the Breast Cancer Pain Questionnaire (BCPQ), which was originally developed by Gartner et al
and used in over 600 patients in our previous studies. The BCPQ includes assessment of
average pain, pain frequency (how many days/week), and pain location (breast, arm, side,
axilla), from which an Pain Burden Index (PBI) can be calculated. The BCPQ also includes
questions about other body pain, seeking medical help for pain, and painkiller use. We will
also use the Brief Pain Inventory (BPI), a well-validated general measure of pain and
disability worst pain, least pain, and interference. We will supplement this with questions
assessing pain with and without movement. We will assess for neuropathic character of pain
using the Leeds Assessment of Neuropathic Symptoms and Signs (S-LANSS).1 The Pain Coping
Questionnaire will be administered to prospectively assay for effective coping strategies
used by patients.
Medical, Anesthetic and Surgical Assessment: Medical variables, including patient's
functional status, will be assessed at the preoperative visit. Using the Weiner preoperative
evaluation center email alert system, the hands-on anesthetist and/or anesthesiologist will
be contacted to inform them on the patient's participation in the study. In order to assess
and adjust for potential impact of anesthetic technique or pharmacological agents on PPMP,
the following data will be collected on the day of surgery: Primary anesthetic method
(volatile agent vs. IV propofol vs. regional/paravertebral), amount and type of local
anesthetic administered, and amount of opioids used (the latter expressed as morphine
equivalent units/hr). In addition, information about other relevant analgesic preoperative or
intraoperative medications will be gathered. Other potentially confounding intraoperative
factors such as vasopressor use/amount, fluids or blood administered, total anesthesia time,
etc. will be recorded. Among this group of breast surgeons, there is relative homogeneity in
anatomical technique and tissue disturbance, although there is some variation in dissection
technique. Detailed assessment of surgical technique will include primary surgeon, duration
of surgery, presence of bilateral surgery, type of surgery (total mastectomy, segmental
mastectomy), performance of nodal dissection (axillary or sentinel node), mass of breast
tissue excised, length of incision, predominant mode of dissection, nerve handling, and
presence and type of reconstruction.
Perioperative acute pain assessment: Initial pain score upon arrival will be assessed by PACU
nursing staff and/or anesthetist. One hour after PACU arrival, patient will be assessed by
research study personnel, being asked to rate pain at rest, with arm movement, and with
maximal deep inspiration using the pain verbal rating scale (VRS). The Perioperative Pain
Service, which is comprised of acute pain specialists, anesthesia residents, and a nurse
practitioner, rounds on postoperative patients on Post-op Day (POD) 0 and 1. Accordingly,
pain scores at rest, with arm movement and with deep inspiration at these two timepoints will
be assessed. In addition, opioid consumption and adjuvant analgesic use will be assessed.
Upon discharge, which is typically on POD1 or 2, total postoperative opioid use/hours of
postoperative time as inpatient will be calculated and expressed in morphine equivalent
units/hr. On postoperative day 1, patients will undergo brief bedside QST (as at preoperative
evaluation, described above), PCS, and Coping Strategies Questionnaire.
Postoperative follow-up and assessment of subacute and persistent pain, changes in
psychosocial and psychophysical functioning: Follow up assessments will be made at 2 weeks, 3
mo, 6 mo, and 1 year. Patients are seen by the primary surgeon or nurse practitioner, as well
as by collaborator Ann Partridge and other oncologists at these times. In collaboration with
these practitioners, we will assess patients' degree of persistent pain using the BCPQ, BPI
and VRS. Additionally, the brief QST and psychosocial questionnaires will be re-administered
at 6 months and 1 year postoperatively.
Collection of sample for future genetic testing: In order to obtain genetic information about
particular sites of variability that may impact post-surgical pain, we will collect saliva
samples from using the Oragene Self-Collection kit. This procedure is non-invasive, safe,
effective, and widely used.
Statistical analysis: The primary outcome measure will be the calculated Pain Burden Index
(PBI) at 1 year post-mastectomy. The PBI at one year post-mastectomy will be tested for
significant associations with potentially predictive preoperatively assessed variables
(psychophysical (QST), psychosocial, demographic, functional, medical and surgical variables)
using t-tests for categorical predictors and linear regression for continuous predictors.
Results of all tests will be summarized with descriptive statistics and both unadjusted
p-values and p-values adjusted using Holm's procedure to control the family-wise error rate.
In terms of data management and analysis, attention will be paid to identification of
multi-colinearity among covariates, and redundant factors may be eliminated from further
multivariable analyses.
Power analysis: Using our cross sectional data, in which roughly 35% of patients experienced
persistent post-mastectomy pain beyond 1 year after mastectomy, a calculated effect size
between pain and no pain groups for each of the psychosocial and psychophysical variables was
determined. Effect sizes, which we assume will be similar in the proposed study, ranged from
0.06 to 0.70. With 200 patients we will have 80% power at a two-sided alpha level of 0.05 to
detect effect sizes of 0.40 or greater, which were observed in 7 of the variables considered.
Further corroborating the feasibility of adequate power with a sample size of 200, several
smaller studies have also detected differences in QST between patients with and without
chronic postsurgical pain after thoracotomy, shoulder surgery, and surgery to correct chest
wall deformation.
psychosocial and psychophysical characteristics, then measures perioperative and long-term
changes to examine the relationship of psychophysical and psychosocial processing to
persistent post-mastectomy pain development .
Preoperative Psychophysical assessment:
Pressure pain testing methods: After giving informed consent, the PI or a fully trained
member of the research staff will administer a brief QST session. Pressure pain threshold and
tolerance will be assessed using a digital pressure algometer (Wagner FDX, Greenwich, CT,
USA) with a flat round transducer, probe area 0.785 cm2. Testing sites will be bilateral on
the dorsal aspect of the proximal forearm (extremity site) and over the trapezius muscle at
the upper back (truncal site). For pressure threshold determination, pressure is increased at
a steady rate of approximately 1 kg/second until subject indicates that the pressure is first
perceived as painful. Pressure pain tolerance will be determined by instructing patients to
indicate the pressure at which the pain was no longer tolerable. Two trials will be performed
at each site.
Temporal Summation testing methods: Mechanical pinprick pain will be assessed using
standardized weighted pinprick applicators similar to those described by Rolke et al99 of two
designated forces (256mN and 512mN) which result in a painful sensation in most
subjects.1-2,100 First, a single stimulation of the lower force pinprick will be applied to
the dorsal aspect of the index finger between the first and second interphalangeal joints of
the each hand while resting palm down on the armrest, and then rated by the subject on a
scale of 0-10. Next, after a break of at least 10 seconds, a train of 10 stimuli will be
applied at the same premarked spot, at a rate of 1 stimulation/second. The subject will rate
pain on a scale of 0-10 after the first, fifth and tenth stimulus, then rate any ongoing pain
15 and 30 seconds after cessation of the last stimulus. The same procedure will be repeated
using the higher force pinprick on the third finger of the each hand. Subjects will undergo
two trials at each force, with a break of at least one minute between trials.
Psychosocial Assessment: Preoperative demographic, medical, psychosocial and pain
questionnaires will be completed by the patient during their preoperative office visit.
Questionnaires assessing psychosocial factors are chosen based upon previous association with
PPMP, strong psychometric validation characteristics, and brevity. The Pain Catastrophizing
Scale (PCS), which has been validated in pain patients and controls, will be used to measure
catastrophic thinking associated with pain. Depressive symptoms, anxiety and sleep
disturbance will be assessed using short-form instruments from the NIH roadmap initiative,
Patient Reported Outcome Measurement Information System (PROMIS), which have been extensively
validated in studies comparing results with established scales, and have been calibrated on
over 20,000 persons. The Brief Symptom Index 18-Somatization Scale, also previously validated
in chronic pain patients,107 will be used to measure somatization.
Pain assessment: The primary pain outcome measure will be Pain Burden Index as measured by
the Breast Cancer Pain Questionnaire (BCPQ), which was originally developed by Gartner et al
and used in over 600 patients in our previous studies. The BCPQ includes assessment of
average pain, pain frequency (how many days/week), and pain location (breast, arm, side,
axilla), from which an Pain Burden Index (PBI) can be calculated. The BCPQ also includes
questions about other body pain, seeking medical help for pain, and painkiller use. We will
also use the Brief Pain Inventory (BPI), a well-validated general measure of pain and
disability worst pain, least pain, and interference. We will supplement this with questions
assessing pain with and without movement. We will assess for neuropathic character of pain
using the Leeds Assessment of Neuropathic Symptoms and Signs (S-LANSS).1 The Pain Coping
Questionnaire will be administered to prospectively assay for effective coping strategies
used by patients.
Medical, Anesthetic and Surgical Assessment: Medical variables, including patient's
functional status, will be assessed at the preoperative visit. Using the Weiner preoperative
evaluation center email alert system, the hands-on anesthetist and/or anesthesiologist will
be contacted to inform them on the patient's participation in the study. In order to assess
and adjust for potential impact of anesthetic technique or pharmacological agents on PPMP,
the following data will be collected on the day of surgery: Primary anesthetic method
(volatile agent vs. IV propofol vs. regional/paravertebral), amount and type of local
anesthetic administered, and amount of opioids used (the latter expressed as morphine
equivalent units/hr). In addition, information about other relevant analgesic preoperative or
intraoperative medications will be gathered. Other potentially confounding intraoperative
factors such as vasopressor use/amount, fluids or blood administered, total anesthesia time,
etc. will be recorded. Among this group of breast surgeons, there is relative homogeneity in
anatomical technique and tissue disturbance, although there is some variation in dissection
technique. Detailed assessment of surgical technique will include primary surgeon, duration
of surgery, presence of bilateral surgery, type of surgery (total mastectomy, segmental
mastectomy), performance of nodal dissection (axillary or sentinel node), mass of breast
tissue excised, length of incision, predominant mode of dissection, nerve handling, and
presence and type of reconstruction.
Perioperative acute pain assessment: Initial pain score upon arrival will be assessed by PACU
nursing staff and/or anesthetist. One hour after PACU arrival, patient will be assessed by
research study personnel, being asked to rate pain at rest, with arm movement, and with
maximal deep inspiration using the pain verbal rating scale (VRS). The Perioperative Pain
Service, which is comprised of acute pain specialists, anesthesia residents, and a nurse
practitioner, rounds on postoperative patients on Post-op Day (POD) 0 and 1. Accordingly,
pain scores at rest, with arm movement and with deep inspiration at these two timepoints will
be assessed. In addition, opioid consumption and adjuvant analgesic use will be assessed.
Upon discharge, which is typically on POD1 or 2, total postoperative opioid use/hours of
postoperative time as inpatient will be calculated and expressed in morphine equivalent
units/hr. On postoperative day 1, patients will undergo brief bedside QST (as at preoperative
evaluation, described above), PCS, and Coping Strategies Questionnaire.
Postoperative follow-up and assessment of subacute and persistent pain, changes in
psychosocial and psychophysical functioning: Follow up assessments will be made at 2 weeks, 3
mo, 6 mo, and 1 year. Patients are seen by the primary surgeon or nurse practitioner, as well
as by collaborator Ann Partridge and other oncologists at these times. In collaboration with
these practitioners, we will assess patients' degree of persistent pain using the BCPQ, BPI
and VRS. Additionally, the brief QST and psychosocial questionnaires will be re-administered
at 6 months and 1 year postoperatively.
Collection of sample for future genetic testing: In order to obtain genetic information about
particular sites of variability that may impact post-surgical pain, we will collect saliva
samples from using the Oragene Self-Collection kit. This procedure is non-invasive, safe,
effective, and widely used.
Statistical analysis: The primary outcome measure will be the calculated Pain Burden Index
(PBI) at 1 year post-mastectomy. The PBI at one year post-mastectomy will be tested for
significant associations with potentially predictive preoperatively assessed variables
(psychophysical (QST), psychosocial, demographic, functional, medical and surgical variables)
using t-tests for categorical predictors and linear regression for continuous predictors.
Results of all tests will be summarized with descriptive statistics and both unadjusted
p-values and p-values adjusted using Holm's procedure to control the family-wise error rate.
In terms of data management and analysis, attention will be paid to identification of
multi-colinearity among covariates, and redundant factors may be eliminated from further
multivariable analyses.
Power analysis: Using our cross sectional data, in which roughly 35% of patients experienced
persistent post-mastectomy pain beyond 1 year after mastectomy, a calculated effect size
between pain and no pain groups for each of the psychosocial and psychophysical variables was
determined. Effect sizes, which we assume will be similar in the proposed study, ranged from
0.06 to 0.70. With 200 patients we will have 80% power at a two-sided alpha level of 0.05 to
detect effect sizes of 0.40 or greater, which were observed in 7 of the variables considered.
Further corroborating the feasibility of adequate power with a sample size of 200, several
smaller studies have also detected differences in QST between patients with and without
chronic postsurgical pain after thoracotomy, shoulder surgery, and surgery to correct chest
wall deformation.
Inclusion criteria:
1. Female
2. Aged 18-80 years
3. Scheduled for total or partial mastectomy
4. Willingness to undergo psychophysical and psychosocial testing
5. Willingness to participate in long-term follow-up
Exclusion criteria:
1. Scheduled for biopsy only
2. Pregnant
We found this trial at
1
site
75 Francis street
Boston, Massachusetts 02115
Boston, Massachusetts 02115
(617) 732-5500
Phone: 612-205-0186
Brigham and Women's Hosp Boston’s Brigham and Women’s Hospital (BWH) is an international leader in...
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