1. Pain Judit Méray MD, Prof. Institute of Anesthesiology and Intensive Therapy

2. Definition of pain I. “A complex experience consisting of a physiological (bodily) response to a noxious stimulus followed by an affective (emotional) response. A warning mechanism that helps to protect an organism by influencing it to withdraw from harmful stimuli. It is primarily associated with injury or the threat of injury, to bodily tissues”. Physical pain is the unpleasant feeling common to a headache and a stubbed toe. It typically consists of unpleasantness, motivation to withdraw or protect, and an awareness of the quality, location, intensity and duration of the pain, though it is possible to experience pain in the absence of one or more of these elements. Pain is often accompanied by negative emotions (e.g., fear, anxiety, rage) and cognitive impairment (e.g., attention and working memory deficits).working memory

3. Definition of pain II. For scientific and clinical purposes, pain is defined by the International Association for the Study of Pain (IASP) as "an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage” International Association for the Study of Pain (Somatic cause/sensation with negative/unpleasant subjective/emotional components) McCaffrey (1968): “whatever the experiencing person says it is, existing whenever he says it does." An abstract concept which refers to: A personal, private, sensation of hurt A harmful stimulus which signals current or impending tissue damage A pattern of responses which operate to protect the organism from harm

4. Pain Originally pain is an important signalling/ warning system:it helps to notice and to avoid harmful stimuli. Pain caused by diagnosed illnesses or by medical intervention is of no use, but causes suffering and gives start to harmful pathophysiologic processes → it must be prevented or eliminated !!!

5. Pain sensation Physiologic: activation of sensory nerveous system - adequate - provisory - localized ti the injury - normal pain threshold - protective - unpleasant emotion Pathologic: changed nervous reaction : - dysfunction of the somatosensory system -inadequate -long lasting -involves non injured regions (secunder zone) -reduced pain threshold, exaggerated reaction -lack of normal selectivity -somatosensory-sympathetic interaction

6. Peripheric origin of pain: Nociceptive  Skin, muscles, viscera, tooth, vessels, neural injury… Neurogenous  Toxins, neuropathy, fibrosis… inflammation Periferic nerve Spinal cord Receptors : skin, muscle, bone, periosteum, joints, dental pulp, pleura, pritoneum, meninxes, GI system, genitals Stimulation of the receptors: mechanical, chemical, termal + algogen substances: K +, serotonin, histamin, bradykinin Sensitizing by: PG, LT, SP, CGRP Transmitter: glutamat (SP, CGRP)

7. The spinal cord „wind up” Continuous/repeated stimuli to the dorsal horn – sensitization of the sensory neurons (stimulus-treshold reduction!) Hyper-sensitivity (longer depolarization time) Cerebral pain sensation amplificated Otherwise not painful stimuli will be considered as pain

8. Central perception of painful stimuli Multidimensional, complex cerebral function:  Sensory-discriminative function (localization)  Cognitive-evaluative function (realization, learning)  Affective- emotional processing Noxious stimulus nociception pain Pain-related behavior suffering + secondary inflammatory reaction

9. Thalamus (n.ventr.posterolat) * * Sensory- discriminative function

10. Chronic pain It starts as an acute pain but it continues beyond the normal time expected for resolution of the problem or persists or recurs for various other reasons. It is not therapeutically beneficial to the patient. It is not therapeutically beneficial to the patient. In acute pain, attention is focused to treat the cause of pain whereas in chronic pain, the emphasis is laid upon reducing the pain to give relief, limit disability and improve function.

11. Because of the complex emotional processing psychic components play a very important role in pain sensation. Anxiety, fear can intensify pain; Patient care, information, reassarance may reduce pain sensation!

12. Judgement of pain intensity 0 max Visual Analog Scale Numeric analog scale 0 1 2 3 4 5 6 7 8 9 10 Verbal Rating Scale: extreme very strong strong mild no pain at all For children: VAS NAS

13. Multidimensional evaluation of pain Characteristics, course, quality of life….

14. The most important questions Where? - the localization of pain -segmental? When? – How long do you experience the pain? What does provoke the start of the pain? How often? Changes in the character of the pain? Fluctuation? Sesonal appearance? How? - quality, characteristics of the pain  Lancinating, stiching, lightning, continuous, spastic, etc. How strong? - scales, scores Accompanying symptoms What gives help/attenuation of pain?

15. Important points of medical help Let the patient speak!!!– TIME!! Physical evaluation General state, habitus, antropometric measures,… Psychosomatic character, neurologic disorders/deficits? Painful spots, areas - continuous pain, or…? Raction to touching (allodynia?) Temperature differences? Others? (edema, muscle strength, sensory function, colour ? etc.) Instreumental diagnostic evaluation Laboratory, X ray, CT, MRI - recognition of pathology requireing surgery or other medical intervention Therapeutic plan: - long term care necessary!  Causal therapy – if possible  Systemic analgetics – + adjuvant therapy (!)  Regional anesthesia techniques  Mechanic/physical therapeutic methods– physicoth, AKU, TENS…..  Invasive methods?

16. Typical exmaples of chronic pain Migrain Tension headache Cluster Cervicogenic Vascular Headaches Primarily neurogenic pain  Trigeminus neuralgia  Herpes zooster  Phantom pain  Sympathetic reflex distrophia - causalgia-forms Central pain -e.g. thalamic pain Ischaemic pain -extremities, mesenteric… Tumor pain: infltration, compression, ulceration, edema, perfusion disturbences Locomotor disorders  Back ache - radicular / non radicular  Shoulder-arm syndrome  Rheumatism – polyarthritis, fibromyalgia, myofascial pain Abdominal pain - e.g. pancreatitis

17. Headache Migrain: unilateral, frontotemporal pain aura, characteristic accompanying syndromes Th: ASA, metoclopramide naproxene or paracetamol Prophylaxis: metoprolol Tension headache – dull, pressing, helmet-like Cluster - unilateral, sudden onset, short, devastating –sesonal appearance Th: indomethacinum, dihydroergotamintartarate Cerviocogenic headache: unilateral, frontotemporal dull pain, influenced by movement, position Headaches caused by drogs - pl.. nitrates, Ca-antagonists….„cameleon” type Adjuvant therapy: physicoth, TENS, relaxation-training Do not concentrate solely on medical therapy! (multimodal approach!)

18. Pain caused by locomotor diesases Rheumatism  Polyarthritis: symmetric appearance (small joints)  Arthrosis: knee, tigh-joint  Fibromyalgia -”tender points”  Myofascial pain – local trigger points Backache Radicular -segmental reflexion! Non radicular Shoulder-arm syndrome Radikular C6-8 (trigger: head movement, rotation, coughing) Intervertebral Scalenus syndrome Periarthritis humerosclapularis Th: NSAIDs, physicoth., TENS, (steroid,) antidepressants Th: bed rest, NSAIDs, physicoth., TENS, AKU, (steroids,) antidepressants Psychotherapy, relaxation training, Learning, active rehabilitation!

19. Disorders of connecting tissues, vasculitis SLE*, Sjögren, rh. arthritis**, scleroderma, polymyositis Polyarteritis nodosa, Wegener granulomatosis, arteritis temporalis, CNS vasculitis…… Laboratory tests: STD? Rheumatoid factor** Antinuclear antibody (ANA)* Anti SM* ……………….

20. Neurogenic pain (compression neuropathy, neuritis, ischemic, deafferentation…) Trigeminus neuralgia  Unilateral, „lightning”-like attacks, triggered by….  Medical therapy: carbamazepine (2x100 mg)  Ganglion blockade: local anesthetics/ Janetta operation Atypical facial pain  Myoarthropathia, masseter spasms, trismus, TMJ – dental rehabilitation  Antidepresssants (amitryptilin) Sympathetic reflex dystrophy  Burning pain, generalized edema of the distal extremity, temperature (autonome) motoric and sensoric difference, trophic disturbances Other pain-syndromes of sympathetic origin Phantom pain -continuous burning pain + sharp, shooting pain - Prevention!  Cause? – prosthesis? Neuroma?, perfusion of the stump?  TENS, sympatheticj blockade/neurolysis The pain reflects to the innervation field of the nerve

21. Ischemic pain  Arterial occlusion of the extremities  Thrombangiitis obliterans  Mesenteric ischemia Neuropathies (diabetic, toxic, alcoholic, etc.)  „burning feet”, „restless leg”  Amyotrophia (myelopathia) – tighs, legs Pancreatitis: epigastrial pain history, labor., US, clinical picture Th: EDA, PCA (antibiotics, steroids…) Th: symp. blockade, EDA antidepressants (amitryptilin) Th: ASA, carbamazepine, antidepressants (amitryptilin) Vitamine B, TENS

22. Tumor pain Curative possibilities? Surgery? Chemotherapy? Irradiation? Origin: infiltration, compression, ulceration,edema, perfusion disturbances (pseudorheumatism, radiculopathy, peripheric neuropathies, plexus syndrome, osteonecrosis…) History, physical examination, consultation with the oncologist/surgeon/radiologist +complemetary investigations (e.g. Se Ca), US, scintigraphy, MRI, etc. Therapeutic plan: Analgesia: – medical therapy (WHO recommendation!) – regional technics Adjuvant therapy: anticonvulsive, antidepressant, sedative, anti-obstipation, anti-osteolytic, etc. Nutrition, psychotherapy, sport, improvement of the general state

23. WHO recommandation for the treatment of tumor pain Week opioids + NSAID Strongopioids + NSAID p.os, sublinqual, transdermal Spinal, epidural, regional blocks invasive

24. Choice of the analgetic plan Prepared protocols for typicalal situations  Starts automatically, without delay  Easier for the medical personal  Simple management even for beginners BUT: Individual reactions and situations should be regarded!  Individual reaction, different pharmacologic effect  individual pharmacokinetics, pharmacodynamics! Treat the patient, who is in pain and not the symptoms!

25. Therapeutic modalities Medical therapy - never alone, as sole therpay! local systemic Psychotherapy Therapeutical equipment (eg. Arch support,othopedic shoes, corset, etc.) Physical therapy methods (physicoth.) (pl. medical gymnastics, massage, hydroth., acupressure, acupuncture, TENS, electric stimulation Neural blockades Interventional pain therapy Surgical intervention - operation or minimal invasive techniques (eg. Janetta op., percutaneous laser technique)

26. Steps before the medical intervention History - most important!!!– let the patient speek! Physical examination general state, antropometric measures, physical abilities psychosomatic state, neurologic disorders/deficits? painful parts, points - continuous pain? Reaction to palpation, tactile stimuli? temperature, edema, other disorders at the painful site? Physical tolerance of the patient? Instrumental diagnostic measures – evaluation X-ray, CT, MRI - diagnosis exclusion of disorders where surgical or other intervention is necessary Therapeutic plan: - long term care of the patient!  Causal therapy  medication: painkillers – adjuvant therapy  regional anesthesia  invasive methods  mechanical therpeutic measures – physioth, AKU, TENS…..

27. Medicinal therapy Ways of application Oral Subcutaneous Intramuscular Intravenous (single, continuous, PCA) Intradural Epidural ( continuous, PCA) Intra(cerebro)vetricular Rectal Intrarticular Intrapleural Transdermal Endotracheal Sublinqual, intranasal Superficial Aim: Basic therapy + therapy of the „break through pain”

28. Analgetic medication Routes:  tablet  suppositorium  sc., im. injection  iv. injection  transdermal  special Administration:  repeated bolus  continuous Applying person:  medical personal  patient (parents)

29. Anelgetics morfine: “gold standard” new systhetic opioids (fentanyl, alfentanil, sufentanil, remifentanil) “agonist-antagonist”: ceiling-effect (nalbuphin) codeine family  oral administration  combinations NSAID  oral administration  opioid dose reduction  If given alone: only for mild - medium pain

30. Non-steroidal antiinflammatory drugs Antiphlogistic action  causal therapy, if the pain is caused by inflammatory mediators Cave: contraindications and possible dangers (gastric ulceration, GI bleeding, MI, thromboembolic complications) !

31. Non-steroidal antiinflammatory drugs Ceiling effect  If given alone, only for moderate pain superficial surgery (e.g. dentoalveolar surgery), ortopedic interventions, etc. Preferred application: po. or supp. In combination: basic analgesia, -nearly always necessary! Synergistic action - „ opioid saving action” better analgesia less side effects

32. pharmaconduration single daily maximum application dose dose form Acetyl salicylic acid4-6 hours0.5-1 g4-5 gp.o. Paracetamol4-6 hours0.5-1 g4 gp.o. Metamizole4-6 hours 0.5-1(-2) g4 gp.o., iv., im. Ibuprofen4-6 hours 200-400 mg3600 mgp.o. Naproxen12 hours 250 mg1375 mgp.o. Diclofenac8-12 hours 25-50 mg100-150mg p.o., iv. Ketorolac6 hours 30 mg120 mgp.o., iv., im. Piroxicam12-24 hours 20-40 mg40 mgp.o., im. Tenoxicam24 hours 20 mg20 mg p.o., iv., im. Nalbuphin3-6 hours 10-30 mg160 mgiv., im. Tramadol4-6 hours 50-100 mg600 mgiv., im. Most common NSDAIDs

33. NSAIDS Indometacine Diclofenac CATAFLAM 50 mg drg. DICLAC, DICLOFENAC, DICLOMEL, FLECTOR, VOLTAREN 50, 75 mg, VOLTAREN DOLO 12,5 mg PiroxicamFELDENE, HOTEMIN TenoxicamTILCOTIL MeloxicamMOVALIS IbuprofenADVIL 200 mg NaproxenAPRANAX 275, 550 mg tbl., NAPROSYN, NAPROXEN Nifluminic acidDONALGIN 250 mg

34. „Others” ASA ALKA SELTZER effervescent tbl ASPIRIN tbl.100, 500 mg, ASPIRIN FORTE, ASPIRIN PLUS C, ASS+C KALMOPYRIN MetamizoleALGOPYRIN 1, 2,5, g (500 mg/ml) Algopyrin complex, Quarelin (metamizole+coffeine+drotaverine) AminophenazonDERMICID, DEMALGON, DEMALGONIL Paracetamol BENURON, EFFERALGAN, MEXALEN, PANADOL, PARACETAMOL, RUBOPHEN Solpadeine, Saridon, Miralgin, Neo Citran Phenacetin combinationsAntineuralgica, (coffeine+amidazophen+phenacetin) DOLOR (aethylmorphine+amidazophen+phenacetin)

35. Narcotic analgesics Morphine Morphinum hydrochloricum 1%, 2%, 3% M-ESLON (10), 30, 60, 100, (200) mg MST CONTINUS 10, 30, 60, 100 mg retard tbl., PALLADONE-SR 4, 8, 16, 24 MG CR 20, 30, 60, 100, 200 mg granulátum (susp.) MST UNO 30, 60, 90, 120, 150, 200 mg retard kapsz. OxycodoneOxycontin 10, 20, 40, 80 mg retard filmtabl. DihydrocodeineDHC Continus 60, 90, 120 mg retard tbl. Pethidine DOLARGAN inj., tabl. Fentanyl DUROGESIC 25, 50, 75, 100 mg/h TTS tapasz 50 mg/ml inj., DOLFORIN… Nalbuphine NUBAIN 20 inj. Accurate documentation, storage necessary!!! CAVE: abuse!

36. Injection in „prn” system Serum conc. t Im. Pain! analgesia Side effects

37. Adjuvant methods Infiltration of the area (subcutaneous, intramuscular) with local anesthestics Intraarticular injection Peripheric blocks - local anesthetics continuous or repeated injection through cannula (axillary, femoral, caudal) Spinal anesthesia with opioids fentanyl, sufentanyl EDA - continuous infusion with syringe pumps, PCA e.g. Marcain 0,1% + Fentanyl 10  g/ml – indul 2-7 ml/hour, PRN ↑ Lidocaine Bupivacaine Ropivacaine

38. Medicinal adjuvant therapy Tricyclic antidepressants Anticonvulsive, spasmolytic medication Anticholinergics Gastric ulcer prevention (H 2 receptor blocking, PPI) Antinauseal therapy Laxativa Anxiolytics Coritcosteroids Antihistamine, sympatholytics, etc.

39. Ways of interrupting the pain afferentation 1.Superficial (surface) anaesthesia (spray, application of anesthetic solutions, gels) 2.Inflitration anesthesia (injection) 3.Conduction type anesthesia (perineural injection, plexus blockade) 4.Ganglion anesthesia 5.Peridural /epidural anesthesia * 6.Spinal /intradural anesthesia ** 7.General anesthesia * **

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41. Non systematic/non medicinal therapy Non invasive methods  TENS  Akupuncture – tradicional, elektric, laser stimulation of the points  Magnetotherapy  Psychotherapy, relaxation training, physicotherapy  Surgery  Infiltration, conduction analgesia  Ganglion blockade – with local anaesthetics– neurolysis  Intradural, epidurals analgesia (local anesthetic, opioids,…) Invasive techniques

42. Inthratecal opioid application Obstetric use Additive (synergistic) application with local anesthetics Postoperative analgesia Improve the effect of EDA Unsuccesful EDA + COPD Attenuation of chronic pain in special situations

43. Important consideration before the use of interventional techniques in chronic pain therapy: Indication – possible effectiveness – possible failure? (motivation, patient compliance, danger of dependency, educational level, accompanying diseases.? Existence period of pain, previous interventions, sympatic components of pain…?) Risk of the intervention? (legal responsibility?) Cost-benefit relation? Patient’s insurance? Necessary documentation? Existence of objective (instrumental) and subjective (personal) conditions? (eg. sterile OR surroundings, equipment, competency, practice, …)

44. Examples of methods at the interventional pain clinic Pulsating radiofrequency treatment of nerve routes  3-500 kHz AC application through isolated needle-electrodes in an intermittent „pulsating” mode – no thermal effect, analgesia achieved by the electric field Percutaneous spinal electro (thermo) radicotomy  3-500 kHz AC through isolated needle-electrodes causes thermal laesion of the nerve roots, causing irreversible, long lasting effect. Epidural neuroplastic method  Through a specially formed epidural cannula, after contrast- identification of the nerve root responsible for the pain, injection of triamcinolon, hyase +local anesthetic. (liberation of the adhered nerve root) Epiduroscopy (diagnostic and therapeutic.)  Introduction of a disposable fiberoptic device into the epidural space (epiduroscope), diagnostic and therapeutic interventions (medicine, lavage, liberation of adhesions, drainage, etc.) Facet anesthesia  „facet” joint: zygophyseal articulation – local anesthesia of the joint and nerve in the chosen segments. Disappearance of pain is of diagnostic value!

45. Important: Everybody has the right to be releaved, from suffering and pain within the bounds of possibility in every period of life. Sometimes there can not be found any organic disorder in the background of pain – even in these situations the pain has to be treated!!! Chronic pain nearly always is associated with psychosocial elements (Need of complex therapy!) ? The relation of the patient  to himself(herself („internal”)  to his/her environments („external”)  Transzcendentally („upwards”) Strong pain is inacceptable!!! (cause is irrelevant)! After exclusion of the possibility of causal therapy an effective symptomatic therapy is necessary! Opioid tolerance ╪ addiction - elevate the dose according to requirement! –but recognize the tricks of the addicts Rule: effective basic therapy + complementary therapy for the „break through pain”! Do not be loath to ask for help, or to send the patient to a pain centre, if necessary!

46. Most important task today: to organize pain clinics under the leadership of well trained pain specialists European Chart of human rights 2002: Everybody has the right to be releaved, from suffering and pain within the bounds of possibility in every period of life Hyppocrates