Management of endometriosis

associated pain: an integrated approach

Catherine Allaire MDCM, FRCSC

Clinical Professor, UBC Dept OB/Gyn Director, UBC Advanced Laparoscopy Fellowship

Medical Director, BC Women’s Centre for Pelvic Pain and Endometriosis

Disclosures

!  Advisory Board: Abbvie, Actavis, Bayer

!  Speaker: Covidien

Objectives

"  Recognize the multiple contributors to endometriosis-associated pain "  Understand the role of central sensitization in chronic pelvic pain "  Become familiar with additional tools that may be helpful for challenging pain issues

Endometriosis

!  Affects 10% of reproductive age women !  Chronic, relapsing disorder, though not always

progressive !  Pelvic pain is the most common presenting

symptom and has the most important clinical burden

Fraser IS. J Hum Reprod Sci 2008 Mahutte NG, Kayisli U, Arici A. Endometriosis in Clinical Practice.2005 SOGC Clinical Practice Guideline. Endometriosis: Diagnosis and management. J Obstet Gynecol Can 2010

Endometriosis-Associated Pelvic Pain: A Clinical

Puzzle !  Pain does not occur in all patients

with endometriosis !  Pain pattern can vary in individual

patient and between patients !  Pain not related to ASRM staging !  Treatments targeted to

endometriosis are not always successful at eliminating pain

!  Some patients will develop chronic pelvic pain

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Clinical Case: Emily #  32 year-old G1P1 with a longstanding history of

dysmenorrhea, deep dypareunia and now worsening pelvic pain.

#  Laparoscopy 2010: Stage 2 endometriosis completely excised, had improvement in symptoms for 2 years

#  Laparoscopy 2013: Stage 1 endometriosis completely excised, 3 months of improvement, then recurrence of pain

# Amenorrheic on progestin treatment

# She is coming to see you because she has heard that you are the best endometriosis surgeon in the area

Emily

# She now has daily, diffuse low pelvic pain with intermittent severe exacerbations

# Dyspareunia is worse; now has introital component; avoiding intercourse; relationship is affected

# Has frequent bloating, alternating diarrhea and constipation; no dyschezia

# Sleep is disturbed; has high anxiety

# Missing a lot of work because of the pain

# Physical exam: diffuse abdominal and pelvic tenderness, no nodularity, endovaginal U/S Normal

Pain Experience

!  Definition: An unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage (IASP)

!  There are no objective measurements for pain !  Pain experience has 3 component: sensory,

emotional and cognitive !  Pain may not be an accurate indication of what is

occurring in the body:

!  We can have a lot of pain with little tissue damage, e.g. paper cut, kidney stone

!  We can have severe pain with no tissue damage, e.g. IBS !  We can have severe tissue damage without pain, e.g. war

injuries

How does endometriosis cause pain?

Recognized mechanisms of pain:

" Nociceptive: somatic or visceral

"  Inflammatory " Neuropathic:

peripheral or central Howard J Minim Invasive Gynecol 2009 Cervero F, Understanding Pain, 2012

Figure adapted from: SOGC Clinical Practice Guideline. Endometriosis: Diagnosis and management. J Obstet Gynecol Can 2010

Suspected Endometriosis

CHC therapy, continuous or cyclic

1. Reconsider diagnosis additional testing and/or non-gynaecologic referrals 2. Chronic pain management and multidisciplinary support

Failure of CHC therapy

Failure of surgical or medical therapy

Laparoscopy for diagnosis and treatment

CHC, combined hormonal contraceptive IUS, intrauterine system

Medical therapy 1.  Progestins 2.  GnRH agonist with addback 3.  Progestin IUS 4.  Danazol

Central Sensitization

An increase in the excitability of the CNS so that normal inputs now evoke exaggerated responses

Woolf, Nature 1983

Associated with structural changes in the brain

Stratton and Berkley Human Reprod Update 2011

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Central Sensitization

!  Hyperalgesia: increased sensation from the same painful stimuli even if sensor is unchanged (eg. menstruation)

!  Allodynia: pain from “non-painful” stimuli (eg. dyspareunia)

Sengupta 2009; Malykhina 2007; Latremoliere and Woolf 2009

Central Sensitization !  Hyperalgesia: increased sensation from a painful

stimuli even if sensor is unchanged (eg. menstruation)

!  Allodynia: pain from “non-painful” stimuli (eg. dyspareunia)

Sengupta 2009; Malykhina 2007; Latremoliere and Woolf 2009

Altered gray matter in endometriosis patients

Endometriosis and pain: decreased gray matter in thalamus, cingulate gyrus, putamen Endometriosis and no pain: increased gray matter in PAG

As-Sanie S. et al, Pain 2012

Peripheral sensitization !  Occurs via:

!  Increase in number of sensors (nerves) !  Increased sensitivity of the sensors (inflammation,

hormones)

!  Endometriosis lesions are associated with increased sensory and autonomic nerve formation and activity

!  Hysterectomy specimens from chronic pelvic pain patients have higher nerve density

!  Therefore the same event/injury results in increased signals sent by sensors

Sengupta, 2009; Malykhina, 2007; Latremoliere & Woolf, 2009

Cross-sensitization !  Single nerve may supply two

different organs !  Nerves from two organs may

converge at the spinal cord !  The brain does not have a very

accurate map of the body

!  Excited sensor from uterus sends signal to spinal cord, but also sends another signal to a different organ (bowel, bladder) (viscero-visceral convergence) or to muscles/skin (viscero-somatic convergence)

Sengupta, 2009; Hoffman, 2011

Cross-Sensitization

!  Bladder: painful bladder syndrome “evil twin”

!  Bowel: irritable bowel syndrome

!  Myofascial: pelvic girdle pain

pelvic floor dysfunction

trigger points `

Tirlapur et al. Int J Surg 2013 Issa et al. Gut 2012

Jarrell J Current Pain Headache Rep 2011

Risk factors !  Predisposing Factors:

!  Genetics !  Exaggerated stress-response !  History of depression, anxiety !  History of physical or psychological trauma

!  Reinforcing factors !  Sleep disturbance !  Anxiety, depression, fear-avoidance !  Operant learning: interpersonal and

environmental reinforcements !  Repeated nociceptive exposure (wind-up)

Instituteforchronicpain.org

What can we do? It is possible to make changes in the pain

experience:

•  Sensors are replaced continuously •  Natural endorphins can block signals •  The nervous system is very adaptable and can

be re-trained •  Many factors can act as “gate control”

Pearson, 2007; McCaffrey, 2003

Education, Lifestyle changes, Mindfulness, CBT

Pelvic Physiotherapy, Medication, Surgery

Evidence

!  Cochrane review of treatment for CPP, 2009 !  One RCT showed multidisciplinary approach to CPP

more successful than standard approach (Peters et al, Ob Gyn 1991)

!  RCT evidence for pain education, CBT and mindfulness based therapy in other arenas of chronic pain

BC Women’s Centre for Pelvic Pain and Endometriosis

!  Gynecologists (+ Fellow) !  Physiotherapist !  Counsellor !  Nurse !  Clerks !  Administrators !  Research coordinator !  Research trainees !  Website: www.womenspelvicpainendo.com

BC Women’s Centre for Pelvic Pain and Endometriosis

!  Clinical !  Laparoscopic surgery for endometriosis (Stages

I-IV) !  Medical management !  Interdisciplinary program

!  Research !  Population (cost, trends, demographics) !  Clinical (online questionnaires) !  Basic (tissue banking, genomics, nerve studies)

Interdisciplinary program !  Gynaecologist assessment

and treatment !  Pain education workshop

(full day) !  Individual physiotherapy

(2-4) !  Individual counselling (CBT/

Mindfuless) (2-4) !  RN case management !  Gynaecologist summary

appointment

NS Sensitization

Gynecologica

l

Musculo-skeletal

Psycho-social

Pain Education

!  Diagnosis and acceptance of central sensitization concept

!  Reframe the problem: stop looking for the issue in the tissue and seeking repeated surgical therapies

!  Focus on function and quality of life

!  Empowerment and hope

Pain Education

!  Butler, D., & Moseley, L. (2003). Explain pain.

!  Caudill, M. (2009). Managing pain before it manages you. 3rd ed.

!  Gardner-Nix, J. (2009). The mindfulness solution to pain: Step-by-step techniques for chronic pain management.

!  Pearson, N. (2007). Overcome pain, live well again. Parts 1 to 3. [Series of 4 Webcasts accessed at: http://www.lifeisnow.ca].

!  You tube video: !  Understanding Pain: What to do about it in less than five

minutes?

Treatment Approach Surgery: !  Diminish or remove triggers of nociceptors

(e.g. endometriosis, menstruation)

Medication: !  Reduction of peripheral sensitization and

inflammation (hormonal suppression)

!  Reduction of central sensitization (neuromodulators)

Treatment Approach Physiotherapy •  Addressing musculoskeletal problems and changing muscle

patterns •  Learning how to increase activity levels without flare-ups •  Restoring normal bowel and bladder function •  Pelvic girdle, pelvic floor, trigger points •  Needling techniques

Mindfulness and CBT •  Takes advantage of “gate control” function of brain and spinal

cord •  Pain management strategies

Lifestyle Changes !  Diet !  Sleep hygiene !  Exercise

Sesti et al., 2007

Patient Engagement !  Booklet to record appointments, diagnoses, treatment plan !  Diet, sleep, stress reduction skills reinforced !  Patient can record own notes, questions, ideas

Passport

Prospective cohort study

!  Started January 2014

!  Online Redcap database

!  Patient: Baseline + Follow-up questionnaires ( 6, 12, 24 months) !  Pain scores (VAS) !  History !  Function and Quality-of-Life (EHP-30) !  Depression (PHQ-9), Anxiety (GAD-7), Pain Catastrophizing

(PCS) !  IBS, PBS, Female Sexual Distress, Kinesophobia

!  Physician: Physical examination, Treatment plan, Surgical findings, Pathology data

Prospective cohort study

!  January – September 2014 (N = 429)

!  Mean age: 34 Average duration of symptoms: 14 years

!  30% have seen 3 or more prior specialists

!  25% have seen 3 or more prior alternative care providers

!  Endometriosis (Confirmed = 55%, Suspected = 24%, None = 21%)

!  Offered interdisciplinary program if at least 2 of the following: (46%) !  Decreased QoL (EHP > 59) !  Psychiatric (PHQ9 > 9, GAD7 > 7, or PCS > 30) !  Sensitization (IBS or PBS) !  Daily opioid use

0% 10% 20% 30% 40% 50% 60%

IBS

PBS

Anxiety

Depression

Catastrophizing

Poor QoL

Daily opioid

Co-morbidities of our cohort

Preliminary data

!  Multiple regression analysis showed that increased severity of CPP is related to: !  Previous child abuse, history of pregnancy, and family

history of chronic pain !  Smoking and irritable bowel syndrome !  Depression score, BMI, and abdominal wall trigger

points

!  Independent of presence or absence of endometriosis

Next Questions

!  Effect of interventions on QoL and pain

!  Which intervention was most useful

!  Can we predict who will benefit from interdisciplinary care

!  Can this model be applied in secondary centers and even primary care settings

Summary

1)  Endometriosis can cause pain via nociceptive, inflammatory and neuropathic mechanisms

2)  Central sensitization is the likely mechanism for chronic pelvic pain unresponsive to usual endometriosis treatments

3)  Early treatment of pain is key to preventing development of sensitization

4)  A multimodal interdisciplinary approach may lead to decreased pain and improved quality of life in these patients

Acknowledgments !  Research Team

!  Fontayne Wong !  Dr. Lien Hoang !  Dr. Ali Yosef !  Dr. Ghadeer Alkusayer !  Jennifer Cheung !  Forson Chan !  Narissa Mawji !  Fahad Alotaibi

!  Funding !  WHRI, UBC FoM, CFWH !  CFI, CIHR

!  Collaborators !  Dr. Mohamed Bedaiwy !  Dr. David Huntsman !  Dr. Lori Brotto !  Dr. Sarka Lisonkova !  Dr. Anna Lee and Tony Ng !  Dr. Christina Williams !  Dr. Paul Yong

!  Support !  BCWH & WHRI !  VGH & OvCaRe !  UBC Dept/Divisions