12/8/2017 Disclosures: Understanding Central None Sensitization Syndromes: Fibromyalgia, Chronic Pelvic Pain, and Painful Bladder Syndrome Molly Heublein, MD molly.heublein@ucsf.edu Assistant Clinical Professor of Medicine UCSF Women’s Health Center of Excellence What is the diagnosis? A painful disorder, more common in women, worsened with hormonal fluctuations and stress, characterized by allodynia and/or Migraine hyperalgesia. No pathognomonic exam finding, lab test, or imaging study confirms this condition. 1
12/8/2017 Myofacial pain Painful bladder syndrome syndrome Irritable Bowel Irritable Bowel Syndrome Syndrome Chronic Pelvic Pain Migraine Migraine Primary Primary Dysmenorrhea Dysmenorrhea Fibromyalgia Chronic Fatigue Chronic Fatigue Syndrome Syndrome Central Sensitization Syndromes Myofacial pain Myofacial pain Painful bladder Painful bladder syndrome syndrome syndrome syndrome Irritable Bowel Irritable Bowel Syndrome Syndrome Chronic Chronic Pelvic Pain Pelvic Pain Migraine Migraine Primary Primary Dysmenorrhea Dysmenorrhea Vulvodynia Vulvodynia Fibromyalgia Fibromyalgia Multiple Chemical Multiple Chemical Chronic Fatigue Chronic Fatigue Sensitivity Sensitivity Syndrome Syndrome Syndrome Syndrome Tempomandibular Tempomandibular joint disorder joint disorder Functional dyspepsia 2
12/8/2017 Objectives for today: Central Sensitization Syndromes Myofacial pain Painful bladder Discuss pain processing and central pain syndrome syndrome Irritable Bowel Syndrome Discuss overlap of fibromyalgia with chronic pelvic pain Chronic Mechanical low back and painful bladder syndrome pain Pelvic Pain Migraine Review fibromyalgia as a classic central sensitization Primary Dysmenorrhea disorder Vulvodynia Fibromyalgia Consider best practices to address patients suffering from these conditions Multiple Chemical Chronic Fatigue Sensitivity Syndrome Syndrome Tempomandibular joint disorder Functional dyspepsia Chronic Overlapping Pain Conditions Clinical Case: 35 yo woman comes to pcp office c/o anxiety and dysuria. Hx of IBS diagnosed at age 22, and chronic pelvic pain diagnosed at age 29. She follows strict diets and takes some medications to help manage both, but does still experience frequent symptoms of nausea, abd bloating, and internal pelvic burning or pulling pain. In the past 2 mo she has noted recurrent episodes of what she thought were UTIs but did not respond completely to antibiotics. She continues to have dysuria, urinary frequency, and bladder pain. 3
12/8/2017 Types of pain Clinical Case: Peripheral Neuropathic 35 yo woman comes to pcp office c/o anxiety and dysuria. (nociceptive) Hx of IBS diagnosed at age 22, and chronic pelvic pain Cause of pain: Mechanical damage or Damage or entrapment inflammation of peripheral nerves diagnosed at age 29. She follows strict diets and takes Responds to: NSAIDS, opioids, local Peripheral and central some medications to help manage both, but does still procedures therapies. Entrapment experience frequent symptoms of nausea, abd bloating, and responds to surgery or internal pelvic burning or pulling pain. injection Classic examples: Acute pain due to injury, Diabetic neuropathy, In the past 2 mo she has noted recurrent episodes of what OA, RA, cancer pain radicular back pain, she thought were UTIs but did not respond completely to postherpetic neuralgia antibiotics. She continues to have dysuria, urinary frequency, and bladder pain. Clinical Case Clinical Case Our patient has undergone: Our patient has undergone: - EGD and Colo X2 over the years - EGD and Colo X2 over the years - modified barium swallow - modified barium swallow - multiple urinalyses - multiple Uas, STI screens - sexually transmitted infection screens - pelvic ultrasound - pelvic ultrasound - CT abdomen Pelvis - CT abdomen Pelvis ALL REPORTED NORMAL 4
12/8/2017 What did you do last time you Types of pain saw a patient like this? Peripheral Neuropathic (nociceptive) A. Refer her to a psychiatrist, this is probably a somatoform disorder. Cause of pain: Mechanical damage or Damage or entrapment inflammation of peripheral nerves B. Tell her there is nothing wrong with her and she should feel Responds to: NSAIDS, opioids, local Peripheral and central procedures therapies. Entrapment better soon. responds to surgery or injection C. Explain the idea of central pain, discourage more advanced The bio-medical model of pain Classic examples: Acute pain due to injury, Diabetic neuropathy, testing, and help establish a treatment plan. OA, RA, cancer pain does not hold up specific radicular back pain, postherpetic neuralgia D. Say “there is nothing wrong with your bladder/GI tract/etc, pathologic findings are not seen in let me refer you to this other specialist who can evaluate most patients with chronic pelvic you more for muscle/uterus/etc problems” pain, painful bladder syndrome, or fibromyalgia Types of pain What did you do last time you saw a patient like this? Peripheral Neuropathic Centralized (nociceptive) Cause of pain: Mechanical damage Damage or entrapment Central disturbance or inflammation of peripheral nerves in pain processing A. Refer her to a psychiatrist, this is probably a somatoform (hyperalgesia/allody disorder. nia) B. Tell her there is nothing wrong with her and she should feel Responds to: NSAIDS, opioids, Peripheral and central Centrally acting local procedures therapies. Entrapment drugs better soon. responds to surgery or C. Explain the idea of central pain, discourage more advanced injection testing, and help establish a treatment plan. D. Say “there is nothing wrong with your bladder/GI tract/etc, Classic Acute pain due to Diabetic neuropathy, Fibromyalgia, examples: injury, OA, RA, radicular back pain, irritable bowel let me refer you to this other specialist who can evaluate cancer pain postherpetic neuralgia syndrome, tension you more for muscle/uterus/etc problems” headache, IC, chronic pelvic pain Adapted from: Clauw D. Fibromyalgia and Related Conditions. Mayo Clinic Proceedings. 90(5). 2015 May, 680-692. 5
12/8/2017 In patients with central sensitization Types of pain are not exclusive, most patients many studies have shown changes in have overlapping pain sensory processing: generators Lower pain thresholds to pressure/heat/cold/electrical stimuli based on subjective reporting (both magnitude and duration of pain sensation) Lower thresholds to auditory and visual stimuli as noxious on subjective reporting Changes in localized brain metabolism and interconnectivity Increased levels of activating cytokines and decreased levels of cytokines in descending inhibitory pathways Reduction in activity of inhibitory pain relieving pathways Hoffman. Central and Peripheral Pain Generators in Women with Chronic Pelvic Pain: Patient Centered Assessment and Treatment. Current Rheumatology Reviews. Volume 11 , Issue 2 , 2015 6
12/8/2017 Responses to painful stimuli vary Genetic basis dramatically in the population Catechol-O-methyltransfease (COMT) is one of several enzymes that breaks down catecholamines This study looked at 202 healthy women, and assessed genetic variation in COMT genes, baseline response to pain, and risk of developing TMJ dysfunction Low pain sensitivity was associated with higher COMT activity levels and reduced risk of developing TMJ Dysfunction Luda Diatchenko et al; Genetic basis for individual variations in pain perception and the development of a chronic pain condition, Human Molecular Genetics , Volume 14, Issue 1, 1 January 2005, Pages 135–143. 7
12/8/2017 Neurotransmitters COMT activity is important for breakdown of dopamine, norepinephrine, epinephrine Higher levels of substance P in the CSF Elevations in CNS glutamate levels in fibromyalgia, measured both in the CSF and directly in the brain using proton spectroscopy (H-MRS) are also found in individuals with fibromyalgia Experience of Pain 16 FM patients and 16 matched controls were exposed to painful pressures during fMRI scanning. - increased neural activations in the primary and secondary somatosensory cortex, the insula, and the anterior cingulate with painful stimuli. - regions of activation were similar for the patients and controls, but the control group needed almost double the pressure to develop the same level of pain Gracely, et al. (2002), Functional magnetic resonance imaging evidence of augmented pain processing in fibromyalgia. Arthritis & Rheumatism, 46: 1333–1343. doi:10.1002/art.10225 8
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