1. PAIN Why, and What To Do About It… Kenneth N. Schikler, MD, Department of Pediatrics, Division of Pediatric Rheumatology University of Louisville School of Medicine

2. Childhood Pain Syndromes 25% of all new patients seen by pediatric rheumatologists 75% female Average age of onset 12 years Pediatric Rheumatology Database Group J Rheum 23(11)1968-74, 1996

3. Musculoskeletal Pain Population based survey of >6600 children and adolescents in Netherlands 82% response rate 25% reported chronic pain Of that group 57% consulted MD Ref: Perquin,et al. Clin J Pain,2000

4. Musculoskeletal Pain (MSP) 6% of visits to a pediatric primary clinic of children>3 y/o was for MSP¹ Low back pain 1 month prevalence in UK among 1496 students 11-14 years old was 24% (pain for >1 day), 94 % reported disability via a disability questionairre² ¹ De Inocencio. Pediatrics, 1998 ² Watson. Arch Dis Child, 2003

5. PAIN is no fun, but…

6. Pain is An unpleasant sensory and/or emotional experience associated with actual or potential tissue damage It is a protective early warning system to alert us to adjust what we are doing in order to assess whether harm or damage might occur

8. Pain Physical recognition of unpleasant stimulus, and… The Cerebral/emotional recognition and response to the unpleasant stimulus

10. Dealing with the cerebral/emotional

11. Dealing with the Cerebral/Emotional Side of Pain Until one is sure that they are safe from harm or damage from an unpleasant stimulus (pain), fear and anxiety complicate and heighten the unpleasant reaction, until someone we trust to have our welfare in mind and is knowledgeable and can reassure us that we are safe, the painful experience and response to it continues at maximal levels

12. Dealing with the Cerebral Component of Pain The highly motivated individual even when “unaware” of an unpleasant stimulus may “ignore” it until the motivation diminishes Examples: athletes, First Responders, military personnel in action or friends or family members in emergencies Often function without conscious recognition of pain until their “need to function” passes

14. Pain : types Nociceptive Neuropathic Central Pain Processing (Central Sensitization)

17. Nociceptive Pain When nerve endings are stimulated to the point approaching a harmful level Thermal: temperature extremes Mechanical: crushing, tearing, piercing of non-nerve tissue Chemical: salt in a wound

19. Neuropathic Pain Insult to portions of a nerve typically with a tingling, burning, “pins and needles” sensation, or a “shooting pain” Obstructive blood flow to a nerve from pressure (hand falling asleep or dysautonomia) Direct trauma (bumping funny bone) Diseases that affect the nerve

21. Central Pain Processing Heightened sensitivity of the areas within the brain that alert us to potential damage at intensity levels that typically would not provoke those pain centers to “activate” When activated in addition to arousing recognition of pain, the physiologic responses to pain are triggered, altering the Autonomic Nervous System’s behavior

23. Inflammatory Arthritis & Pain IL-1 IL-6 TNF- MMP’s

24. JIA, Cytokines & Pain Cytokines in the joint have a direct effect on nerve endings, and also on the joint lining and cartilage causing inflammation and swelling. This puts mechanical pressure on nerve endings in addition to the direct chemical nerve stimulation and promotes other pain inducing substances Within the central nervous system these cytokines and other chemicals make the pain centers more “alert” to pain

26. Pain & Inflammatory Arthritis: Treatment NSAID’s Acetaminophen DMARD’s Biologics Moderate exercise Treatment aimed at minimizing the bradykinin, Substance P, prostaglandins, MMP’s, and pro-inflammatory cytokines

28. N-methyl-D-aspartate (NMDA)

31. Chronic MSK/Central Pain Processing & Related Disorders Fibromyalgia Chronic Fatigue Migraine Irritable Bowel Syndrome TMJ disorders Mood Disorders Complex Regional Pain Syndrome (RSD) Chronic Pelvic Pain Premenstrual Syndrome Myosfascial Pain syndromes Multiple Chemical Sensitivities Chronic cystitis Dysautonomia/ POTS

33. Pain above and below the waistIn addition, axial skeletal pain (cervical spine, anterior chest, thoracic spine, or low back pain) must be present. Low back pain is considered lower segment pain. Pain in 11 of 18 tender point sites on digital palpationDefinition: Pain, on digital palpation, must be present in at least 11 of the following 18 tender point sites Digital palpation should be performed with an approximate force of 4 kg. A tender point has to be painful at palpation, not just "tender." The American College of Rheumatology 1990 Criteria for the Classification of FM[13,25]

34. Juvenile Fibromyalgia (JFS) Widespread MSP for at least 3 months ≥ 5 well-defined tender points 3 of 10 minor criteria ≤age 16 at onset If 5 minor criteria present only 4 tender points needed Ref: Yunis & Masi. Arthritis Rheum;28(2):138,1985

35. Juvenile Fibromyalgia: Minor Criteria Fatigue Sleep problems Anxiety/ tension Subjective swelling Numbness/tingling Lightheadedness/ dizziness Chronic headache Irritable Bowel syndrome Pain modulated by stress Pain modulated by weather Pain modulated by physical activity

36. Juvenile Fibromyalgia 1756 school-aged (pre-adolescent) Finnish children prospectively studied by questionnaire then PE; 1.3% prevalence 338 healthy Israeli 9-15 y/o students studied; 6.2% prevalence 1.3% healthy Mexican 9-15 y/o students 1 in 6 people with fibromyalgia are less than 18 years old

37. New ACR Criteria for Fibromyalgia (preliminary) Remove tender points from criteria as the central element Quantitate widespread pain with widespread pain index (WPI) Incorporate key symptoms Provide symptom severity scale (SS) Ref: Arthritis Care Res;62(5):600-10,2010

38. Fibromyalgia & rCBF Fibromyalgia patients and controls detect sensory stimuli at the same levels (electric, thermal, mechanical) Level at which stimuli become noxious is ~twice as high for controls Similar stimuli produce significant differences in regional Cerebral Brain Flow; >2x’s in pts vs controls, particularly in the Anterior Cingulate Cortex

39. FMS : rCBF

40. Central Pain Processing Disorders & Catastrophizing Responses that characterize pain as being “awful” “horrible”, “unbearable” Found to be independent of Depression May influence intentional focus on painful or potentially painful events Increases pain-related fear leading to increased attention to stimuli and amplifying perception of pain rCBF similar to that found in Fibromyalgia

41. Catastrophizing & rCBF

42. Mood Stress & The Brain

44. Fibromyalgia & Other Central Pain Syndromes:Treatment Validation Education Pharmacologic Aerobic Exercise Cognitive Behavior Therapy Alternative Therapies

45. Validation & Education Acknowledge the presence of discomforting symptoms of these conditions (not diseases) Provide an explanation for our understanding of how these mechanisms occur Prevent “sick mode” identification

46. Sleep Hygiene Bed is for sleep only No naps Regular bedtime No vigorous exercise within 2 hrs of bedtime No more than 30 minutes of sleeplessness in bed Relaxation, self-guided imagery techniques

47. Cognitive Behavioral Therapy Modules of pain management, psycho-education, sleep hygiene & ADL’s Instruction in cognitive restructuring, distraction, relaxation and self-reward Minimize catastrophizing style of coping Focus on regaining function via developing self-management skills

48. Exercise (I) Aerobic nearly universally beneficial; tolerance, compliance, adherence are biggest issues To maximize benefits: Both physician and patient should consider this as a “drug” Assure physiologic capability ( eg exclude EIA) Review/instruct in how to measure heart rate/pulse Review availability of access to aerobic exercise equipment in home

49. Pharmacologic Treatment of Central Pain Antidepressants Mixed norepinephrine/serotonin reuptake inhibitors Anticonvulsants Alpha-2-delta (α2δ) ligands Opioid receptor antagonists Future Central alpha-2-adrenergic agonist Dopamine receptor agonists NMDA receptor antagonists NK-1 receptor antagonist GABA receptor agonists Vitamin D (??)