Learning Objectives. Pain in Kids with Neurofibromatosis: Prevention and Treatment. 5-year old Marius: Procedural Pain Management

Transcription

1 Pain in Kids with Neurofibromatosis: Prevention and Treatment Stefan J. Friedrichsdorf, MD, FAAP Medical Director, Department of Pain Medicine, Palliative Care & Integrative Medicine Children's Hospitals and Clinics of Minnesota, Minneapolis/St. Paul, MN Associate Professor of Pediatrics, University of Minnesota Medical School Learning Objectives Review prevalence of pain in children with Neurofibromatosi Discuss different kind of pains in children with NF Discuss successful interdisciplinary approaches in managing chronic pain and primary pain disorders in children Appreciate low importance of pharmacotherapy 5-year old Marius: Procedural Pain Management Redningskvinder Channel Tv3 - (Episode 7, Season 4.) 2014

2 Don't have enough staff for pediatric pain control...? Funny, how there is always enough staff to restrain a child. Pediatric Analgesia in 1985 Papoose Boards Neurofibromatosis & Pain Neurofibromatosis type 1 (NF1) causes pain Wolters, P.L., et al., Pain interference in youth with neurofibromatosis type 1 and plexiform neurofibromas and relation to disease severity, social-emotional functioning, and quality of life. Am J Med Genet A, A(9): p Plexiform neurofibromas (PNs) common and potentially debilitating complications of neurofibromatosis 1; benign nerve-sheath tumors associated with significant pain and morbidity because they compress vital structures Impact of NF1 from an individual's perspective (60 adults): 1) cosmetic burden of disease 2) learning difficulties 3) concerns about the risk of passing NF1 to offspring 4) uncertain disease progression, and 5) pain. Crawford, H.A., et al., The Impact of Neurofibromatosis Type 1 on the Health and Wellbeing of Australian Adults. J Genet Couns, (6): p

3 Neurofibromatosis & Pain Plexiform neurofibromas PNs and other physical manifestations of NF1 can result in severe acute, neuropathic and chronic pain. PNs may cause nerve Citak et al., 2008, airway, and spinal cord compression, leg length discrepancies, and scoliosis Kim et al.2009 Furthermore, pain is associated with PNs Creange et al.1999; Nguyen et al., 2011, which tend to grow most rapidly during childhood Needle et al., 1997; Dombi et al., Pain also may emerge after tumor removal Creange et al., Common nontumor physical manifestations causing pain include skeletal complications Elefteriou et al., 2009 and headaches Creange et al.1999; DiMario and Langshur, Over 70% of children and adults with NF1 use prescription pain medications Creange et al.1999; Pediatric Pain - Status Quo Under treatment of pain in children Parents expect pain to be relieved Forgeron PA, Finley GA, Arnaout M. Pediatric pain prevalence and parents' attitudes at a cancer hospital in Jordan. J Pain Symptom Manage. 2006; 31(5): Priorities of parents of hospitalized children "Taking care of pain" rated as second highest priority (1st: getting right diagnosis) Ammentorp J, Mainz J, Sabroe S. Parents priorities and satisfaction with acute pediatric care. Arch Pediatr Adolesc Med 2005;159: Parents greatest distress: failing to protect their child from pain Tiedeman, M. (1997). Anxiety responses of parents during and after the hospitalisation of their 5 - to -11 year old children. Journal of Pediatric Nursing, 12(2), Melnyk BM. Intervention studies involving parents of hospitalized young children: an analysis of the past and future recommendations. J Pediatr Nurs Feb;15(1):4-13. Assumption: everything possible is done Anand s neonatal surgery studies Pediatric Pain - Status Quo USA: adults receive more than two - three times as many analgesic doses as children (with identical diagnoses) (1) Eland JM, Anderson JE: The experience of pain in children. In: Jacox A (ed). Pain: a source book for nurses and other health care professionals. Boston: Little Brown & C0; 1977: (2) Beyer JE, DeGood DE, Ashley LC, Russell GA. Patterns of postoperative analgesic use with adults and children following cardiac surgery. Pain Sep;17(1): (3) Schechter NL, Allen DA, Hanson K. Status of pediatric pain control: a comparison of hospital analgesic usage in children and adults. Pediatrics Jan;77(1):11-5. The younger children are, the less likely they receive appropriate analgesia Broome ME, Richtsmeier A, Maikler V, Alexander M. Pediatric pain practices: a national survey of health professionals. J Pain Symptom Manage May;11(5): ; Nikanne E, Kokki H, Tuovinen K. Postoperative pain after adenoidectomy in children. Br J Anaesth Jun;82(6): Compared to adults, pediatric patients receive fewer and/or incorrectly dosed analgesics in daily routine Ellis, J. A., O Connor, B. V., Cappelli, M., Goodman, J., Blouin, R., & Reid, C. W. (2002). Pain in hospitalized pediatric patients: How are we doing? Clinical Journal of Pain, 18,

4 Inappropriate Analgesia: Why Bother...? Children with persistent pain suffer more physical symptoms in adult life, more anxiety and more depression 1946 Medical Research Council and 1958 National Child Development Study Inadequate analgesia for initial procedures in children diminishes effect of adequate analgesia in subsequent procedures Weisman SJ, Bernstein B, Schechter NL: Consequences of inadequate analgesia during painful procedures in children. Arch Pediatr Adolesc Med :147-9 Up to 25% of adults have fear of needles with most fears developing in childhood: avoidance of health care (including non-adherence with vaccination schedules Taddio A, Chambers CT, Halperin SA, et al. Inadequate pain management duringchildhood immunizations: the nerve of it. Clin Ther 2009;31(Suppl 2):S ) Pain ratings at 4-6 months routine vaccination higher for circumcised versus uncircumcised boys Taddio A, Katz J, Ilersich AL, Koren G. Effect of neonatal circumcision on pain response during subsequent routine vaccination. Lancet. 1997;349(9052): Neurofibromatosis & Pain Impact of pain in kids with NF1 and plexiform neurofibromas Wolters, P.L., et al., Pain interference in youth with neurofibromatosis type 1 and plexiform neurofibromas and relation to disease severity, social-emotional functioning, and quality of life. Am J Med Genet A, A(9): p Pain interferes with child's daily functioning despite 33% taking pain medication Parents: more symptoms of anxiety & larger tumor volumes predicted greater pain interference greater pain interference, worse depressive symptoms, and more disease complications predicted poorer QOL Adolescents: more symptoms of anxiety predicted greater pain interference greater pain interference and social stress predicted poorer QOL social-emotional problems mediate the relationship between pain interference and QOL. pain interferes with daily functioning in the majority of youth with NF1 and PNs even when using pain medication. So, how do we treat the individual child with NF & pain in front of us? Hmhh... Spoiler Alert: Crystal-clear answer on 3rd last slide!

5 No Needless Pain Multimodal Analgesia What are we measuring...? (1) Nociceptive Pain: arises from the activation of peripheral nerve endings (nociceptors) that respond to noxious stimulation [e.g. localized, sharp, squeezing, stabbing, or throbbing] Somatic (for example, muscles, joints) Chronic somatic pain typically well localized & often results from degenerative processes (such as arthritis) (2) Visceral (internal organs) [poorly localized, dull, crampy, or achy] (3) Neuropathic Pain: resulting from injury to, or dysfunction of, the somatosensory system. [burning, shooting, electric, or tingling] Central pain: caused by a lesion or disease of the central somatosensory nervous system (4) Psycho-social-spiritualemotional Pain / Total Pain (5) Persistant (Chronic) Pain Pain beyond expected time of healing How Do We Manage Acute Pain in Children?

6 Nociceptive Pathways & Primary Sites of Action of Analgesics Aδ or C fiber Injury Nociceptive Pathways & Primary Sites of Action of Analgesics Thalamus 2nd Neuron Aδ or C fiber Acetaminophen (Paracetamol) Injury NSAIDs Multimodal (Opioid-sparing) Analgesia Basic Analgesics Acetaminophen / Paracetamol NSAIDs

7 Citius, Altius, Fortius...? Ibuprofen salts: fast-acting formulations Moore, R.A., et al., Faster, higher, stronger? Evidence for formulation and efficacy for ibuprofen in acute pain. Pain, (1): p Advil Film-Coated Tablets, contains 266 mg of ibuprofen sodium (equivalent to 200 mg of standard ibuprofen) Produced significantly better analgesia over 6h, fewer remedications than standard formulations 200-mg fast-acting ibuprofen (NNT 2.1; 95% confidence interval ) was as effective as 400 mg standard ibuprofen (NNT 2.4; 95% CI ), with faster onset of analgesia. More rapid absorption, faster initial pain reduction, good overall analgesia in more patients at the same dose, and probably longer-lasting analgesia, but with no higher rate of patients reporting adverse events. However, earlier onset preferred in other pain condition, such as chronic nociceptive or neuropathic pain? Peloso, P.M., Faster, higher, stronger: to the gold medal podium? Pain, (1): p Ibuprofen-Sodium Multimodal (Opioid-sparing) Analgesia Basic Analgesics Acetaminophen / Paracetamol NSAIDs Opioids Tramadol ( weak ) Morphine ( strong ) 4 WHO- Principles By the clock PRN ( as needed ) PRN = Patient Receives Nothing When pain is constantly present, analgesics should be administered, while monitoring side-effects, at regular intervals At analgesic dosing: no sedation expected

8 Nociceptive Pathways & Primary Sites of Action of Analgesics Thalamus Opioids Pre-synaptic nerve terminal i Neurotransmitter release Post-synaptic nerve terminal: hmembrane hyperpolarization 2nd Neuron => suppress neuronal excitability Aδ or C fiber Opioids Acetaminophen (Paracetamol) Injury NSAIDs Regular (!) Pain Assessment One-dimensional selfreport scores Multi-dimensional rating scores Pain in children with impaired communication Non-communicating Children s Pain Checklist - Revised (NCCPC-R); postoperative Version (NCCPC-PV) Breau LM, McGrath PJ, Camfield CS, Finley GA. Psychometric properties of the non-communicating children's pain checklist-revised. Pain 2002;99(1-2): Pediatric Pain Profile (PPP) Hunt A, Goldman A, Seers K, Crichton N, Mastroyannopoulou K, Moffat V, Oulton K, Brady M. Clinical validation of the paediatric pain profile. Dev Med Child Neurol 2004;46(1):9-18. r-flacc Malviya S, Voepel-Lewis T, Burke C, Merkel S, Tait AR. The revised FLACC observational pain tool: improved reliability and validity for pain assessment in children with cognitive impairment. Paediatr Anaesth 2006;16(3):

9 Which Opioid to choose? Recommended Tramadol Morphine Fentanyl Oxycodone NOT Recommended Codeine Hydrocodone/Acetaminophen (e.g. Vicodine ) Oxymorphone Oxycodone/Acetaminophen (e.g. Percocet ) Hydromorphone Methadone Multimodal (Opioid-sparing) Analgesia Non-Opioids Acetaminophen / Paracetamol NSAIDs Integrative Therapies Such as: Massage Distraction Deep Breathing Biofeedback Aromatherapy Hypnosis Opioids Tramadol ( weak ) Morphine ( strong ) 4 WHO- Principles By the clock Integrative modalities Integrative modalities effective in management of pediatric pain Hunt, K.; Ernst, E. The evidence-base for complementary medicine in children: A critical overview of systematic reviews. Arch Dis Child 2011, 96, ; Friedrichsdorf, S.; Kuttner, L.; Westendorp, K.; McCarty, R. Integrative pediatric palliative care. In Integrative pediatrics, Culbert, T.; Olness, K., Eds. Oxford University Press: pp ; Evans, S.; Tsao, J.C.; Zeltzer, L.K. Complementary and alternative medicine for acute procedural pain in children. Alternative therapies in health and medicine 2008, 14, include hypnosis Kuttner, L.; Friedrichsdorf, S.J. Hypnosis and palliative care. In Therapeutic hypnosis with children and adolescents., 2nd ed.; Crown House Publishing Limited: Bethel, 2013; pp ; Richardson, J.; Smith, J.E.; McCall, G.; Pilkington, K. Hypnosis for procedurerelated pain and distress in pediatric cancer patients: A systematic review of effectiveness and methodology related to hypnosis interventions. J Pain Symptom Manage 2006, 31, yoga Bussing, A.; Ostermann, T.; Ludtke, R.; Michalsen, A. Effects of yoga interventions on pain and pain-associated disability: A metaanalysis. The journal of pain : official journal of the American Pain Society 2012, 13, 1-9.; Evans, S.; Moieni, M.; Taub, R.; Subramanian, S.K.; Tsao, J.C.; Sternlieb, B.; Zeltzer, L.K. Iyengar yoga for young adults with rheumatoid arthritis: Results from a mixed-methods pilot study. J Pain Symptom Manage 2010, 39, acupuncture Vas, J.; Santos-Rey, K.; Navarro-Pablo, R.; Modesto, M.; Aguilar, I.; Campos, M.A.; Aguilar-Velasco, J.F.; Romero, M.; Parraga, P.; Hervas, V., et al. Acupuncture for fibromyalgia in primary care: A randomised controlled trial. Acupunct Med massage Verkamp, E.K.; Flowers, S.R.; Lynch- Jordan, A.M.; Taylor, J.; Ting, T.V.; Kashikar-Zuck, S. A survey of conventional and complementary therapies used by youth with juvenile-onset fibromyalgia. Pain Manag Nurs 2013, 14, e biofeedback Blume, H.K.; Brockman, L.N.; Breuner, C.C. Biofeedback therapy for pediatric headache: Factors associated with response. Headache 2012, 52, guided imagery Dobson, C.E.; Byrne, M.W. Original research: Using guided imagery to manage pain in young children with sickle cell disease. The American journal of nursing 2014, 114, 26-36; test 37, 47.

10 Integrative Pain Management State of the art pain management in the 21st century demands that pharmacological management must be combined with supportive and integrative, non-pharmacological therapies to manage a child's pain. Mind body program (the Relaxation Response Resiliency Program for neurofibromatosis [3RP-NF]) delivered via group videoconferencing resulted in sustained improvement in QoL (RCT; n=63 adults) Vranceanu, A.M., et al., Mind-body therapy via videoconferencing in patients with neurofibromatosis: An RCT. Neurology, (8): p year-old Cassandra with severe pain due to chest tube insertion Fentanyl PCA the pump and blowing bubbles going to bubble land Nociceptive Pathways & Primary Sites of Action of Analgesics Thalamus Periaqueductal grey (endorphins) Integrative (non-pharmacological) therapies Descending Inhibition + 2nd Neuron Descending pathways that modulate transmission of nociceptive signals originate in periaqueductal gray, locus coeruleus, anterior cingulate gyrus, amygdala & hypothalamus: are relayed through brainstem nuclei in the PEG and medulla to spinal cord. Inhibitory transmitters involved in these pathways incl. norepinephrine, 5-hydroxytryptamine, dopamine, & endogenous opioids. Opioids Acetaminophen (Paracetamol) Aδ or C fiber Injury NSAIDs

11 How does this stuff work...? The periaqueductal gray and descending pain modulation: Hemington KS, Coulombe MA. The periaqueductal gray and descending pain modulation: Why should we study them and what role do they play in chronic pain? Journal of neurophysiology. Feb :jn Distraction significantly increased activation of cingulo-frontal cortex including orbitofrontal & perigenual anterior cingulate cortex (ACC), as well as periaquaeductal gray (PAG) & the posterior thalamus. Active distraction techniques, such as imagery, appear to modulate endorphine release in the midbrain, including the periaqueductal grey and thereby increase activity of descending inhibiting pathways thereby decreasing nociception from the dorsal horn resulting in gate pain modulation during distraction. Valet M, Sprenger T, Boecker H, et al. Distraction modulates connectivity of the cingulo-frontal cortex and the midbrain during pain--an fmri analysis. Pain. Jun 2004;109(3): ; Tracey I, Ploghaus A, Gati JS, et al. Imaging attentional modulation of pain in the periaqueductal gray in humans. The Journal of neuroscience : the official journal of the Society for Neuroscience. Apr ;22(7): ; Derbyshire SW, Osborn J. Modeling pain circuits: how imaging may modify perception. Neuroimaging clinics of North America. Nov 2007;17(4): , ix.; Bingel U, Wanigasekera V, Wiech K, et al. The effect of treatment expectation on drug efficacy: imaging the analgesic benefit of the opioid remifentanil. Sci Transl Med. Feb ;3(70):70ra14 Nociceptive Pathways & Primary Sites of Action of Analgesics Thalamus CORTEX: -Stress - Anxiety - Catastrophizing - Depression - perceived injustice - disturbed Sleep ON OFF 2nd Neuron Periaqueductal grey (endorphins) Integrative (non-pharmacological) therapies Aδ or C fiber Opioids Acetaminophen (Paracetamol) Injury NSAIDs Multimodal (Opioid-sparing) Analgesia Non-Opioids Acetaminophen / Paracetamol NSAIDs Integrative Therapies Such as: Massage Distraction Deep Breathing Biofeedback Aromatherapy Hypnosis Opioids Tramadol ( weak ) Morphine ( strong ) 4 WHO- Principles By the clock Rehabilitation Exercise Physical Therapy Sleep Hygiene Occupational Therapy Speech Therapy Psychology CBT

12 Graded Motor Imagery Process of thinking about moving without actually moving. Gray Matter: Cortical reorganization and associated changes in somatosensory cortex activity and anatomy in certain types of pain Gustin SM, Peck CC, Cheney LB, Macey PM, Murray GM, Henderson LA. Pain and plasticity: is chronic pain always associated with somatosensory cortex activity and reorganization? The Journal of neuroscience : the official journal of the Society for Neuroscience 2012;32(43): ; Vartiainen N, Kirveskari E, Kallio-Laine K, Kalso E, Forss N. Cortical reorganization in primary somatosensory cortex in patients with unilateral chronic pain. J Pain 2009;10(8): degree of cortical reorganization correlated with pain intensity Mirror Visual Feedback Multimodal (Opioid-sparing) Analgesia Non-Opioids Acetaminophen / Paracetamol NSAIDs Integrative Therapies Such as: Massage Distraction Deep Breathing Biofeedback Aromatherapy Hypnosis Opioids Tramadol ( weak ) Morphine ( strong ) 4 WHO- Principles By the clock Rehabilitation Exercise Physical Therapy Sleep Hygiene Occupational Therapy Speech Therapy Psychology CBT Regional Anesthesia Neuraxial infusion Peripheral/Plexus Nerve block Neurolytic block Intrathecal port/pump Intraventricular opioids? Percutaneous cervical cordotomy? Regional anesthesia approaches to pain management in PC Regional anesthesia: pediatric knowledge limited to case reports and case series: Rork, J.F., C.B. Berde, and R.D. Goldstein, Regional anesthesia approaches to pain management in pediatric palliative care: a review of current knowledge. J Pain Symptom Manage, (6): p Neurolytic Sympathectomy: Amr YM, Makharita MY. Neurolytic sympathectomy in the management of cancer pain-time effect: a prospective, randomized multicenter study. J Pain Symptom Manage. Nov 2014;48(5): e942. central neuraxial infusions peripheral nerve and plexus blocks or infusions neurolytic blocks implanted intrathecal ports & pumps for baclofen, opioids, local anesthetics, and other adjuvants RCT (n=109) inoperable abdominal or pelvic cancer: better pain control, less opioid consumption, and better quality of life

13 Neuropathic Pain Pain arising as a direct consequence of a lesion or disease affecting the somatosensory system (IASP 2008) Grading System: (1) Definite, (2) Probable; (3) Possible ( but, not all lesions in the somatosensory system lead to neuropathic pain) Management of Neuropathic Pain in Pediatrics Suggested Non-Evidence-based Step-by-Step Approach (8) NMDA-receptor-channel blocker [ α- agonist? IV lidocaine? Botox A? benzodiazepine? SNRI? Capsaicin?] (7) Lidocain patch (if localized pain). (6) Tricyclic Antidepressant and gabapentinoid (5) Tricyclic Antidepressant (or gabapentinoid) ± low-dose ketamine (4) NEW (!) onset: Opioid analgesics [consider Tramadol or Methadone] plus NSAID (3) Regional anesthesia, if appropriate (2) Integrative therapies & Rehabilitation: manage comorbidities (anxiety, sleep disturbances). Psychological Therapies. (1) Identify and treat underlying disease process (radiation?) (corticosteroids?) Multimodal (Opioid-sparing) Analgesia Friedrichsdorf S: 8th Annual Pediatric Pain Master Class, Minneapolis, MN, June 20-26, 2015 Non-Opioids Acetaminophen / Paracetamol NSAIDs Integrative Therapies Such as: Massage Distraction Deep Breathing Biofeedback Aromatherapy Hypnosis Opioids Such as: Tramadol ( weak ) Morphine ( strong ) 4 WHO- Principles By the clock Psychology CBT Rehabilitation Exercise Physical Therapy Sleep Hygiene Occupational Therapy Child Life Regional Anesthesia Neuraxial infusion Peripheral/Plexus Nerve block Neurolytic block Intrathecal port/pump Intraventricular opioids? Percutaneous cervical cordotomy? Adjuvants Such as: Alpha-Agonist Gabapentinoids TCA/Antidepressants NMDA-Antagonists Na-channel blockers Antispasmodics Benzodiazepines Corticosteroids Muscle relaxants Radiopharmaceuticals Bisphosphonates

14 Neurofibromas & Pain Trials Sirolimus (mtor inhibitors clinically used as anticancer and immunosuppressant drugs) Hua, C., et al., Sirolimus improves pain in NF1 patients with severe plexiform neurofibromas. Pediatrics, (6): p. e ; Weiss, B., et al., Sirolimus for progressive neurofibromatosis type 1- associated plexiform neurofibromas: a neurofibromatosis Clinical Trials Consortium phase II study. Neuro Oncol, (4): p n=24 children selumetinib (oral selective inhibitor of MAPK kinase (MEK) 1 and 2): partial response Dombi, E., et al., Activity of Selumetinib in Neurofibromatosis Type 1-Related Plexiform Neurofibromas. N Engl J Med, (26): p Sorafenib: Children with NF1 and PN did not tolerate sorafenib at doses substantially lower than in children with malignant solid tumors Kim, A., et al., Phase I trial and pharmacokinetic study of sorafenib in children with neurofibromatosis type I and plexiform neurofibromas. Pediatr Blood Cancer, (3): p Chronic Pain in Children Pain lasting > 3-6 months: Time definition arbitrary Pain that extends beyond the expected period of healing hence lacks the acute warning function of physiological nociception Turk DC, Okifuji A. Pain terms and taxonomies of pain. In: Bonica JJ, Loeser JD, Chapman CR, Turk DC, Butler SH. Bonica's management of pain. Hagerstwon, MD: Lippincott Williams & Wilkins; 2001; Treede RD, Rief W, Barke A, et al. A classification of chronic pain for ICD-11. Pain. Jun 2015;156(6): Catastrophizing [ Awfulizing ] A set of negative emotional / cognitive processes such as magnification, rumination and pessimism about pain sensations and feelings of helplessness when in pain. Rumination: Parent anxious preoccupation with pain Magnification: Parent amplification of the significance of pain Significant link between child and parent catastrophizing Lynch-Jordan, A.M.; Kashikar-Zuck, S.; Szabova, A.; Goldschneider, K.R. The interplay of parent and adolescent catastrophizing and its impact on adolescents' pain, functioning, and pain behavior. Clin J Pain 2013, 29, Kids have higher pain ratings, if either child or mother displays high pain catastrophizing Birnie, K.A., et al., Dyadic analysis of child and parent trait and state pain catastrophizing in the process of children's pain communication. Pain, (4): p

15 Fear of Pain Plays a significant role in relation to functional disability and depressive symptoms in the context of pediatric chronic pain Simons LE, Kaczynski KJ, Conroy C, Logan DE. Fear of pain in the context of intensive pain rehabilitation among children and adolescents with neuropathic pain: associations with treatment response. J Pain 2012 Dec; 13(12): Appears to play both a facilitative and inhibitory role in relation to treatment response: may hinder improvements in disability & depressive symptoms declines are strongly associated with positive functional outcomes Adolescents with chronic pain less likely to believe benign interpretations of ambiguous bodilythreat information than controls; associated with more disability xheathcote LC, Jacobs K, Eccleston C, Fox E, Lau JY. Biased interpretations of ambiguous bodily threat information in adolescents with chronic pain. Pain. 2017;158(3): Chronic Pain Pathophysiology Many different chronic and recurrent pain syndromes, in both adult and pediatric populations, are now considered manifestations of an underlying vulnerability rather than separate disorders von Baeyer CL, Champion GD. Commentary: Multiple pains as functional pain syndromes. Journal of pediatric psychology. [Comment] May;36(4): Considerable evidence, especially from twin studies, points to a role of shared biological sensitivity: pain vulnerability, pain sensitivity, or central sensitivity syndrome (1) von Baeyer CL, Champion GD. Commentary: Multiple pains as functional pain syndromes. Journal of pediatric psychology. [Comment] May;36(4): (2) Kindler LL, Bennett RM, Jones KD. Central sensitivity syndromes: mounting pathophysiologic evidence to link fibromyalgia with other common chronic pain disorders. Pain Manag Nurs Mar;12(1): (3) Williams FM, Spector TD, MacGregor AJ. Pain reporting at different body sites is explained by a single underlying genetic factor. Rheumatology (Oxford) Sep; 49(9): (4) Mayer EA, Bushnell Mc: Functional pain syndromes: presentation and pathophysiology. Seattle: IASP Press, 2009 (5) Burri, A., et al., Chronic widespread pain: clinical comorbidities and psychological correlates. Pain, (8): p Neurofibromatosis & Pain youth with NF1exhibit Wolters, P.L., et al., Pain interference in youth with neurofibromatosis type 1 and plexiform neurofibromas and relation to disease severity, social-emotional functioning, and quality of life. Am J Med Genet A, A(9): p learning problems and cognitive deficits display social-emotional difficulties, including higher rates of internalizing and externalizing disorders fewer friends more social problems compared to normative samples or their unaffected siblings

16 Chronic Pain Pathophysiology Biology Genetics (40-50%)* Microtrauma Infection Injury Social Early life stressors = aquired vulnerability (50-60%)* School Adverse Events Parents: Catastrophizing Disordered Pain Processing: Imprecise encoding of threat? Fear of Pain; Catastrophizing Functional Pain Syndrome Primary Pain Disorder Psychology Anxiety Depression Stress Sensitivity * Stephen McMahon: Neurobiological basis for pain vulnerability. #IASPCongress2016 * Moseley GL, Vlaeyen JW. Beyond nociception: the imprecision hypothesis of chronic pain. Pain. 2015;156(1): Primary Pain Disorders Primary headaches Centrally mediated abdominal pain syndrome (2016) Widespread musculoskeletal pain ( fibromyalgia ) CRPS? Majority of children experience pain at multiple sites

17 Pediatric Pain Clinics USA & Canada Interdisciplinary Pain Clinic Excerpt From Little Stars By Moonshine Movies (58Min; 2014) The Exit Interview Pain is real! Positive Expectation = Selffulfilling prophecy? Close collaboration with specialist of underlying acute condition to ensure no injury will be caused by rehab treatment Pediatrics Genetics Hematology/Oncology etc.

18 "Healing Environment" Pain, Palliative & Integrative Medicine h"ps://vimeo.com/ Exit Interview: What is the Hard Work...and non-negotiable...? Exit Interview á á Pain Stress áá Grumpy Anxiety

19 Exit Interview á á Pain Stress áá Grumpy Anxiety Attending School Exit Interview: What is the Hard Work...and non-negotiable...? Physical Therapy Daily home exercise Integrative Medicine Self-Hypnosis Biofeedback Progressive Muscle relaxation Daily home exercise Passive: Massage, Acupuncture Psychology (...if missing school) Normalize Life Sports/Exercise Sleep-hygiene Social: Having daily fun School: Attending full-time (or school-re-entry plan) Family Coaching Medications...??? Opioids & Chronic Pain Lack of evidence supporting long-term effectiveness Escalating misuse of prescription opioids including abuse and diversion Uncertainty about incidence of adverse drug events Chapman CR, Lipschitz DL, Angst MS, Chou R, Denisco RC, Donaldson GW, et al. Opioid pharmacotherapy for chronic non-cancer pain in the United States: a research guideline for developing an evidence-base. J Pain Sep;11(9): ; Elliot JA, Horton E, Fibuch EE: The endocrine effects of long-term oral opioid therapy: A case report and review of the literature. J Opioid Manage (2): endocrine dysfunction (androgen deficiency) Immunosupression & infectious disease Opioid-induced hyperalgesia Xerostomia Overdose Falls & fractures Psychosocial complications

20 Opioids & Chronic Pain Updated Cochrane Review: Effectiveness/safety of long-term opioid therapy for lower back pain remains unproven Chaparro, L.E., et al., Opioids compared with placebo or other treatments for chronic low back pain: an update of the Cochrane Review. Spine (Phila Pa 1976), (7): p Even after adjusting for substantial number of potential confounders, opioids were associated with worse functioning in back pain patients at 6-month follow-up Ashworth, J., et al., Opioid use among low back pain patients in primary care: Is opioid prescription associated with disability at 6-month follow-up? Pain, (7): p Chronic lower back pain: Increase in opioid use associated with increase in depression, and increase in depression associated with increase in opioid dose Scherrer JF, Salas J, Lustman PJ, Burge S, Schneider FD, Residency Research Network of Texas I. Change in opioid dose and change in depression in a longitudinal primary care patient cohort. Pain. Feb 2015;156(2): patients with chronic pain over 7 years: NO relation between opioid dose change and clinical pain score Chen L, Vo T, Seefeld L, Malarick C, Houghton M, Ahmed S, et al. Lack of correlation between opioid dose adjustment and pain score change in a group of chronic pain patients. J Pain 2013 Apr;14(4): Low-dose Amitriptyline (stimulates) 2. Gabapentin (inhibits) Exit Interview 3. Acetaminophen 4. Ibuprofen (Celecoxib?) 5. Lidocain 5% patch 6. Melatonin 7. Vitamin D? 8. SSRI? 9. Co-Q10, Fish-Oil/Omega 3000, Peppermint oil (coated) [for abdo pain]? Opioids in the absence of tissue injury or inflammation not indicated! Multimodal Analgesia Multimodal (opioid-sparing) analgesia: Multiple agents, interventions, rehabilitation, psychological and integrative therapies act synergistically for more effective pediatric pain control with fewer side effects than single analgesic or modality Multimodal = Awesome! 2016 Guidelines on the Management of Postoperative Pain Management of Postoperative Pain: A Clinical Practice Guideline From the American Pain Society, the American Society of Regional Anesthesia and Pain Medicine, and the American Society of Anesthesiologists' Committee on Regional Anesthesia, Executive Committee, and Administrative Council Tegethoff, M., et al., Comorbidity of Mental Disorders and Chronic Pain: Chronology of Onset in Adolescents of a National Representative Cohort. J Pain, (2): p (Adults): Multimodal analgesia therapy (versus PCA only) reduces length of hospitalization in patients undergoing surgery Michelson, J.D., R.A. Addante, and M.D. Charlson, Multimodal analgesia therapy reduces length of hospitalization in patients undergoing fusions of the ankle and hindfoot. Foot Ankle Int, (11): p

21 4 steps to make needles less painful 1. Numb the skin 2. Sugar water or breastfeeding for babies 3. Comfort positioning 4. Distraction Watch videos at childrensmn.org/comfortpromise. Do you remember Marius...? How about a Plan B?

22 LET Anesthesia Sitting upright Distraction Topical Anesthesia 3mL LET-gel: Lidocaine 4%- Epinephrine 0.18% - Tetracaine 0.5% Singer AJ, Stark MJ. Pretreatment of lacerations with lidocaine, epinephrine, and tetracaine at triage: a randomized double-blind trial. Acad Emerg Med Jul;7(7): What s Plan B? If adequate procedural analgesia not feasible with the 4 Non-Negotiables alone, refer patient to: (1) Child Life (should t have been involved by now?) (2) Needle Phobia: psychology (CBT) (2) Mild sedation: Nitrous gas Zier, J. L. and M. Liu (2011). "Safety of high-concentration nitrous oxide by nasal mask for pediatric procedural sedation: experience with 7802 cases." Pediatric emergency care 27(12): or (3) Moderate/deep sedation (e.g. ketamine, propofol) Note: A sedative alone (such as a benzodiazepine) can never be a substitute for procedural analgesia. So, how do we treat the individual pain patient in front of us? Crystal clear answer: Σωκράτη Sōkrátēs; 470/ BC

23 Blog: Pain Chronic Pain Psychological pain Mental Health Anxiety Nociceptive Pain Deconditined Neuropathic Pain Depression Social Pain Poor sleep hygiene School absenteeism Spiritual Pain Visceral Pain Racial Disparity Delirium Total Pain Withdrawal Further Links The New York Times (June 28, 2016) Why Aren t We Managing Children s Pain? Covering Dr. Stefan Friedrichsdorf The New York Times (Dec 16, 2015) essay by Dr. Stefan Friedrichsdorf When a Baby Dies opinionator.blogs.nytimes.com/2015/12/16/when-a-baby-dies/?_r=1 Video: Kiran Stordalen and Horst Rechelbacher Pediatric Pain, Palliative and Integrative Medicine Clinic Tour vimeo.com/ Children s Comfort Promise: Doing everything possible to treat and prevent pain. Eliminating Needle Pain in children (Feb 2015) Staff video: Short Movie: Meet the Interdisciplinary Chronic Pain Clinic Team at Children s Minnesota: LittleStars TV Video: Tour of the Kiran Stordalen and Horst Rechelbacher Pediatric Pain, Palliative and Integrative Medicine Clinic at Children's Hospitals and Clinics of Minnesota and an overview of the three programs that are offered at Children's under this clinic. Short Movie: LittleStarsFilm 'Kali's Story - Beyond the NICU': This amazing pediatric palliative care short movie (7 min) features 8-year-old Kali's journey at Children's Hospitals and Clinics of Minnesota from NICU to today, receiving care by the Pain & Palliative & Integrative Medicine program while inpatient, in the clinic, and at home (Jan 22, 2015) Pain Clinic Appointments: phone Further Training Contact: CIPPC@ChildrensMN.org 11th Annual Pediatric Pain Master Class Minneapolis, Minnesota, USA June 9-15, Education in Palliative & End-of-life Care [EPEC] Become an EPEC-Peds Trainer Conference. Minneapolis, MN. April 12-13, Professional Development Workshop:. Minneapolis, MN. April 14, th International Symposium on Pediatric Pain (ISPP) Basel, Switzerland, June 16-20, Stefan J. Friedrichsdorf, MD, FAAP Medical Director, Department of Pain Medicine, Palliative Care & Integrative Medicine Associate Professor of Pediatrics, University of Minnesota Medical School Children's Hospitals and Clinics of Minnesota 2525 Chicago Ave S Minneapolis, MN USA phone fax stefan.friedrichsdorf@childrensmn.org