Management of Different Types of Pain Prof Lucas

Management Of Different Types Of Pain

KRT Lucas Meliala

Guru Besar Luar BiasaBagian Ilmu Penyakit Saraf

Fakultas Kedokteran Universitas Gadjah Mada, Yogyakarta

Symposium Clinical UpdateYogyakarta, Januari 2011

Curriculum VitaeNama : Prof. dr. KRT. Lucas Meliala, SpKJ, SpS(K).Tempat/tanggal lahir : Membang Muda (Sumut),

22 September 1941Alamat : Jl. Nagan Lor 70, JogjakartaTelepon : (0274) 450758Fax. : (0274) 374052Mobile : 0815 687 0584E-mail : [email protected]

Pendidikan : Lulus Dokter tahun 1969, alumnus FK-UGMLulus Spesialis Saraf & Jiwa tahun 1974

alumnus FK-UI, FK-UGM, FK UnairPekerjaan : Staf Fakultas Kedokteran UGM

bagian IP Saraf sejak tahun 1968 sampai sekarangOrganisasi : 1999-2007 :

Ketua Pokdi Nyeri Perdossi Anggota IASP, ENSKetua Governing board IPS

Definisi Nyeri

Nyeri adalah pengalaman sensorik dan emosional yang tidak menyenangkan akibat kerusakan jaringan, baik aktual maupun potensial, atau yang digambarkan dalam bentuk kerusakan tersebut

Meliala et al., 2002, Pokdi Nyeri Perdossi

Klasifikasi Nyeri

Nyeri

Adaptif

Maladaptif

Inflamasi

Nosiseptif

Fungsional

Neuropatik

Heat

Cold

Intense

ForceMechanical

Heat

Cold

PainAutonomic Response

Witdrawal Reflex

Nociceptor sensory neuron

NOCICEPTIVE PAINNoxius Pheripheral Stimuli

Spinal cord

Brain

Macrophage

NeutrophilGranulocyte

Tissue Damage

Spontaneous PainPain Hypersensitivity

Reduced Threshold : AliodynaIncreased Response : Hyperalgesia


INFLAMANTORY PAINInflammation

Spinal cord

Mast Cell

Brain


Peripheral Nerve Damage

NEUROPATHIC PAIN

Spinal cord Injury

Brain

Normal PeripheralTissue and Nerves

FUNCTIONAL PAIN

Abnormal CentralProcessing


Brain

NOCICPTOR

NOCICPTOR

NOCICPTOR

PERCEPTION

MODULATION

CONDUCTION

TRANSDUCTION

PAIN – SERIES OF EVENTS

PAIN

TRANSMISSION

“Rasa sakit adalah hak istimewa kita”

Nyeri Inflamasi

• Nyeri akibat kerusakan jaringan atau proses inflamasi

• Dapat bersifat spontan atau dibangunkan

• Berguna untuk mempercepat penyembuhan

Meliala, 2004

Heat

Cold

Intense

ForceMechanical

Heat

Cold

PainAutonomic Response

Witdrawal Reflex


NOCICEPTIVE PAIN

Noxius Pheripheral Stimuli

Spinal cord

Brain

Modifikasi Meliala, 2005

ExamplesPeripheral• Postherpetic neuralgia• Trigeminal neuralgia• Diabetic peripheral neuropathy• Postsurgical neuropathy• Posttraumatic neuropathyCentral• Poststroke painCommon descriptors2

• Burning• Tingling• Hypersensitivity to touch or cold

Examples

• Pain due to inflammation• Limb pain after a fracture• Joint pain in osteoarthritis• Postoperative visceral pain

Common descriptors2

• Aching• Sharp• Throbbing

Examples

• Low back pain with radiculopathy

• Cervical radiculopathy

• Cancer pain• Carpal tunnel

syndrome

Mixed PainPain with

neuropathic and nociceptive components

Neuropathic PainPain initiated or caused by a primary lesion or dysfunction

in the nervous system (either peripheral or

central nervous system)1

Nociceptive PainPain caused by injury to

body tissues (musculoskeletal,

cutaneous or visceral)2

PRESENTATION ACROSS PAIN STATES VARIES

1. International Association for the Study of Pain. IASP Pain Terminology.2. Raja et al. in Wall PD, Melzack R (Eds). Textbook of pain. 4th Ed. 1999.;11-57

Presenter

Presentation Notes

This slide illustrates three broad categories of pain: neuropathic (pathologic), nociceptive (physiologic), and mixed pain states that encompass both nociceptive and neuropathic components, with examples of common causes of each type of pain. The key talking points on this slide are as follows: Neuropathic pain has been defined by the International Association for the Study of Pain as ‘initiated or caused by a primary lesion or dysfunction in the nervous system’.1 Depending on where the lesion or dysfunction occurs within the nervous system, neuropathic pain can be peripheral or central in origin. Causes of peripheral neuropathic pain include postherpetic neuralgia (PHN) and diabetic peripheral neuropathy (DPN). Due to the prevalence and characteristics of PHN and DPN, these states may be considered representative of peripheral neuropathic pain. Nociceptive pain is an appropriate physiologic response that occurs when specific peripheral sensory neurons (nociceptors) respond to noxious stimuli. Nociceptive pain has a protective role because it elicits reflex and behavioral responses that keep tissue damage to a minimum. Acute pain, such as that seen with tissue inflammation and chronic pain, such that accompanying osteoarthritis, are examples of nociceptive pain. Although there are no specific descriptors for each type of pain, neuropathic pain is frequently described as ‘burning or tingling’ in quality, while nociceptive pain is often described as ‘aching or throbbing’. There are cases in which an individual experiences pain sensations that are a blend of pain having a nociceptive and a neuropathic origin. For example, in carpal tunnel syndrome, it is common experience to have nociceptive pain, felt around the wrist, and neuropathic pain, felt in the distribution territory of the median nerve (fingers). References International Association for the Study of Pain. IASP Pain Terminology. Raja et al. in Wall PD, Melzack R (Eds). Textbook of pain. 4th Ed. Edinburgh, UK: Harcourt Publishers Limited. 1999.;11-57 Additional key words: descriptor

HEAT

CHEMICAL

PRESSUREBRAINPANASPEGELPERIH


Na+

Nociceptor Peripheral Terminal

H+

Heat

Pinch

Cold

ATP

Heat

HeatH+Capsaicin

NOCICEPTIVE TRANSDUCTION

NaV 1.8/1.9

PAIN

EXAMPLE OF CHRONIC NOCICEPTIVE PAIN: OSTEOARTHRITIS OF THE KNEE

Normal joint Osteoarthritis

Synovial membrane

Cartilage

Synovialfluid

Jointcapsule

Inflammationas bones rub

together

Thinned cartilage

Presenter

Presentation Notes

This slide shows the differences between a joint affected by osteoarthritis and a normal joint. Osteoarthritis, a degenerative condition of the joint, is an example of a condition that causes chronic nociceptive pain.

Nyeri Neuropatik

Nyeri yang disebabkan oleh lesi atau disfungsi pada sistem saraf

Meliala, 2004

“Berbuatlah dan cintailah tanpa memperhitungkan kebahagiaanmu sendiri,dan engkau akan berbahagia sepanjang waktu”

WHAT IS NEUROPATHIC PAIN?

• Pain initiated or caused by a primary lesion or dysfunction in the peripheral or central nervous system

• Pain often described as shooting, electric shock-like, burning – commonly associated with tingling or numbness

• The painful region may not necessarily be the same as the site of injury. Pain occurs in the neurological territory of the affected structure (nerve, root, spinal cord, brain)

• Almost always a chronic condition (e.g. postherpetic neuralgia, poststroke pain)

• Responds poorly to conventional analgesics

Presenter

Presentation Notes

Note to speaker: this slide contains an animated build. The first bullet appears automatically, then click on the slide to bring up the remaining 4 bullets sequentially. The painful region may not necessarily be the same as the site of injury. Pain occurs in the neurological territory of the affected structure (nerve, root, spinal cord, brain). In peripheral neuropathic pain, it is in the territory of the affected nerve or nerve root. In central neuropathic pain, it is related to the site of the lesion in the spinal cord or brain. Neuropathic pain responds poorly to conventional analgesics. There is some evidence to show that opioids may have efficacy in the management of neuropathic pain.


Peripheral Nerve Damage

NEUROPATHIC PAIN

Spinal cord Injury

Brain


Ectopic DischargesNerve lesion induces hyperactivity due to changes in ion channel function

Ectopic discharges

Nerve lesion

Spinal cordNociceptive afferent fiber

Descendingmodulation

Ascendinginput

Perceived pain

Intact tactile fiber

Central sensitizationAfter nerve injury, increased input to the dorsal horn can induce central sensitization

Perceived pain

Ascendinginput


Nerve lesion

Nociceptive afferent fiber

Tactilestimuli

Perceived pain(allodynia)

Ascendinginput


Abnormal discharges induce central sensitization

Pathophysiological Mechanisms Of Neuropathic Pain

Lancet Neurology 2010;9:807-19 Modifikasi Meliala, 2010

Spinal cord dorsal horn

C-fibre

Skin

Aδ or Aβ fibre

Skin

C-fibre

C-fibre

C-fibre

Aδ or Aβ fibre

Opioid receptorNMDA receptorNE/5HT receptorGABA receptorα-adrenoceptorTRPV1 receptorAMPA/KA receptorChemokine receptorCytokine receptorSodium channelCalcium Channel(Α2-δ subunit)

Α2-δ subunit

Chemokine receptor

Cytokine receptorAMPA/KA receptor

Baron et al., 2010

EXAMPLE OF NEUROPATHIC PAIN:ULNAR NERVE LESION FOLLOWING BONE FRACTURE

Ulnar nerve

Presenter

Presentation Notes

This slide shows ulnar nerve damage, caused by direct trauma or compression following an elbow fracture, which can result in neuropathic pain. The nerve damage involves destruction of the myelin sheath of the nerve or part of the�nerve (axon). Direct nerve trauma is a key cause of neuropathic pain. The pain exists after tissue healing and no longer represents an alert to injury, but indicates dysfunction within the nervous system.

Peripheral nociceptors

Ascendinginput


EXAMPLE OF NEUROPATHIC PAIN:ULNAR NERVE LESION FOLLOWING BONE FRACTURE

Trauma leadingto nerve lesion

Perceived pain

Impulses generatedwithin ulnar nerve

Spinal cord

Lesion

“Gedung-gedung makin tinggi namun sumbu amarah kita makin pendek”

Presenter

Presentation Notes

Note to speaker: this slide contains an animated build to represent the involvement of the nervous system in neuropathic pain (ulnar nerve lesion following bone fracture). Clicking on this slide will cause subsequent components of this build to appear automatically.� In ulnar nerve damage, neuropathic pain is caused by direct trauma or compression of the nerve following elbow fracture. Damaged nerve fibers generate abnormal impulses that are transmitted along the sensory (afferent) nerves to the dorsal roots where they enter the spinal cord to reach the dorsal horn. Abnormal impulses over-stimulate the second-order neurons ascending to the cortex through various pathways (brain stem, thalamus, limbic system, and other cortical areas) where pain awareness develops. In neuropathic pain, a lesion or dysfunction of the nervous system may cause an excess of function (positive symptoms) or a deficit of function (negative symptoms): Positive symptoms – spontaneous pain, allodynia (pain due to a stimulus�that does not normally provoke pain), dysesthesia, paresthesia, and hyperalgesia Negative symptoms – weakness or loss of sensation (e.g. wrist and hand flexion following ulnar nerve damage).

NEUROPATHIC PAIN PREVALENCE RANGES FROM 6.0-7.7% IN EUROPE

0123456789

10

UK France Germany Spain

% o

f pat

ient

s

Patients with axial back pain with a neuropathic component included in the surveyData on file. Pfizer Inc. Neuropathic Pain Patient Flow Survey

7.5%6.4%

6.0%

7.7%

Modified Meliala, 2007

Presenter

Presentation Notes

The prevalence rate of Neuropathic pain in European countries ranges from 6,0 – 7,7 % However there is no such data from Indonesia

Normal PeripheralTissue and Nerves

FUNCTIONAL PAIN

Abnormal CentralProcessing


Brain

Presenter

Presentation Notes

In Functional Pain, there is no peripheral lessions, however there is excitation in central neurons. This, may be caused by such decrease of inhibition due to various factors. In example: in fibromyalgia

Nyeri Fungsional

• Nyeri akibat abnormalitas sistem saraf pusat, berupa peningkatan sensitivitas terhadap berbagai stimuli

• Dahulu dikenal dengan nyeri psikogenik

Woolf, 2004, Meliala, 2004

PENYAKIT, KESAKITAN, ATAU KEDUANYA

SAKIT

SAKITPenyakittanpa

kesakitan

Penyakit dankesakitan

Kesakitantanpa

penyakit

Ulkus (luka)Tanpa Ulkus ( tidak luka)

Nyeri perutfungsional yang kronik

BERU A M E

Somatic symptoms that might be considered in reaching a diagnosis of

fibromyalgia

Wolfe et al. Arthritis Care Res 2010;62:600-610

• Muscle pain/weakness• Fatigue/tiredness• Cognitive problems• Headache• Abdominal pain/cramps• Numbness/tingling• Dizziness• Insomnia• Depression• Constipation• Nausea• Nervousness• Chest pain

• Fever• Diarrhoea• Dry mouth• Itching• Wheezing• Raynaud’s phenomenon• Hives/welts• Ringing in ears• Vomiting• Heartburn• Oral ulcers• Seizures• Dry eyes

• Loss of appetite• Rash• Sun sensitivity• Hearing difficulties• Easily bruised• Hair loss• Frequent urination• Painful urination• Bladder spasms• Loss of taste• Change in taste• Blurred vision• Shortness of breath

Presenter

Presentation Notes

Somatic symptoms that might be considered in reaching a diagnosis of fibromyalgia * Here is a selection of symptoms that a physician might commonly consider when considering a diagnosis of fibromyalgia

ID Pain Questionnaire1. Did the pain feel like pins and needles ?

Yes (+1 point) No (0 points)2. Did the pain feel hot/burning ?

Yes (+1 point) No (0 points)3. Did the pain feel numb ?

Yes (+1 point) No (0 points)4. Did the pain feel like electrical shocks ?

Yes (+1 point) No (0 points)5. Is the pain made worse with the touch of

clothing or bedsheets ?Yes (+1 point) No (0 points)

6. Is the pain limited to your joints ?Yes (-1 point) No (0 points)

ID Pain Score Card-1 Neuropathic pain not likely0 Neuropathic pain less likely1 Neuropathic pain less likely2 Consider neuropathic pain3 Consider neuropathic pain4 Strongly consider neuropathic pain5 Strongly consider neuropathic pain

Minimum total score = -1Maximum total score = 5

Burning, feeling like the feet are on fire

Stabbing, like sharp knives Lancinating, like electric shocks

Freezing, like the feet are on ice, although they feel warm to touch

Modified by Meliala 2006

• TO CURE IS SOMETIMES• TO TREAT IS OFTEN• TO COMFORT IS ALWAYS

The task of a doctor:

A. Pare (1598)

PERILAKU NYERI(PAIN BEHAVIOUR)

PENDERITAAN(SUFFERING)

NYERI(PAIN)

BIOPSIKOSOSIAL(BIOPSYCHOSOCIAL)

NOSISEPSI(NOCICEPTION)

PENGERTIAN MODEL NYERI

BYERS AND BONICA, 2001MODIFIKASI PENULIS

•Terapi kognitif•Restorasi fungsional

•Opioid•Tramadol

•Oxcarbazepine•Gabapentin

•Eperisone HCL•Paracetamo

•OAINS

•Antidepresan•Psikotropika•Relaksasi•Spiritual

•Diklofenak•Etodolac•Dexketoprofen•Celecoxib•Modalitas fisik

“Rasa senang dan rasa sakit adalah kembar”

MECHANISTIC APPROACH TO TREATMENT OF NeP

BRAIN

SPINAL CORD

PNSCentral SensitizationCa++ : Lyrica, GBP,OXC,LTG,LVTNMDA : Ketamine, TPM

DextromethorphanMethadone

OthersCapsaicinNSAIDsCox inhibitorsLevodopa

DescendingInhibitorsNE/5HTOpiate receptors

PeripheralSensitization

Na+CBZOXCPHTTCATPMLTGMexiletineLidocaine

TCAsDuloxetinSSRIsSNRIsTramadolOpiates

Beydoun, 2002

Modified by MELIALA, 2006

“Sukacita yang besar selalu didahului oleh penderitaan yang hebat”

MECHANISTIC APPROACH TO TREATMENT

BRAIN

SPINAL CORDPNS

Central Sensitization

Beydoun, 2002

Modified by MELIALA 2006

Ectopic Discharge

Descending Inhibition

“Pengetahuan makin berlimpah, namun kemampuan kita untuk menilai makin tumpul”

Pengobatan Nyeri Neuropatik Saat ini

• Ditujukan untuk mengurangi kepekaan neuron di sistema nervorum perifer dan sentral dengan memodulasi aktivitas saluran ion (GBP, PGB, CBZ)

• Meningkatkan mekanisme inhibisi endogen (TCA, Duloxetine, opioid, Tramadol) dan hasilnya belum memuaskan

• Mengapa?????

Watkins & Maier, 2002; Scholz & Woolf, 2007

EFNS guidelines for the treatment ofpainful polyneuropathy

• Drugs with established efficacy include PREGABALIN, gabapentin, TCAs, SNRIs,, strong opioids and tramadol

EFNS: European Federation of Neurological Societies

First line therapy PREGABALIN/gabapentin or TCAs/SNRIs (evidence level A)

Second line therapy Opioids and lamotrigine (evidence level B)

Lack of orweak efficacy

SSRIs, capsaicin, mexiletine, oxcarbazepine and topiramate (evidence level A)

Low strength evidence or safety concerns Carbamazepine and valproate

Recommendations:

Presenter

Presentation Notes

The European Federation of Neurological Societies (EFNS) has produced guidelines for the assessment of neuropathic pain, which cover appropriate clinical examinations and laboratory tests. The evidence levels refer both to effective and ineffective treatments. Level A for “first line therapy” indicates that there is substantial evidence supporting treatment efficacy. In contrast, level A for “Lack of or weak efficacy” indicates that there is a large amount of evidence demonstrating inefficacy rather than simply insufficient data to support efficacy. [A manuscript has been accepted by the European Journal of Neurology and is due for publication in early 2006 (Attal N, et al.)]

0

10

20

40

%patients

Royal M et all, AAPM 17th Annual Meeting Feb 2001

OXCARBAZEPINE IN NEUROPATHIC PAIN :PROSPECTIVE OPEN-LABEL TRIAL

Excellent

Patients’ subjective respone

30

50

Good Fair Poor(>70%) (51-70%) (20-50%) (<20%)

Antineuralgic of Choice: Peripheral Sensitization (n=207)

7%

18%23%

61%

0%

20%

40%

60%

80%

100%

OXC/CBZ TPM TA Other

% o

f Par

ticip

ants

R. Harden et al.The Journal of Pain, Vol.3 Nr.2 Suppl.1April 2002

OXC=Oxcarbazepine; CBZ=Carbamazepine;TPM= Topiramate;TCA=Tricyclic Antidepressant; Other=Phenytoin,lamaotrigin,Mexiletine, Lidocaine

OXCARBAZEPIN ADVANTAGE IN NEUROPATIC PAIN

• No monitoring of hematologic parameters required

• Fewer drug-drug interaction• No autoinduction of metabolisme• Comparable efficacy• Twice-daily schedule.• Therapeutic effect maybe detected in 24-48

hours

Trileptal usage by indication cumulative since launch

Psychiatric37%

Seizure40%

Pain23%

USA, Scott-Levin PDDA; June 2001

Multidisciplinary approach to management

Initial symptom of pain, fatigue, etc• Disordered sensory processing• Neuroendocrine disturbances

Pharmacological therapies to improve symptoms

Functional consequences of symptoms• Distress• Decreased activity• Isolation• Poor sleep• Increased appetite• Maladaptive illness behaviors

Dadabhoy D, Clauw DJ. Nat Clin Pract Rheumatol 2006;2:364-372.

Nonpharmacological therapiesto address dysfunction

• Strike a balance between pharmacological and non-pharmacological approaches

Presenter

Presentation Notes

Multidisciplinary approach to management Effective management of fibromyalgia requires a multidisciplinary approach, with the need for a balance between pharmacological and non-pharmacological approaches. Pharmacological therapies should be used to improve symptoms such as pain and fatigue, which occur as a result of disordered sensory processing and neuroendocrine disturbances On the other hand, non-pharmacological treatments are needed to address the functional consequences of these symptoms, such as distress, reduced activity, isolation, insomnia, appetite changes, and maladaptive illness behaviours

Management of fibromyalgia: Recommended treatment approach• Multidisciplinary therapy individualized to patients’ symptoms and presentation is recommended• A combination of nonpharmacological and pharmacological therapies may benefit most patients

Mease P. J Rheumatol 2005;32:6-21; Carville et al, [published online ahead of print July 20, 2007] Ann Rheum Dis Doi:10.1136/ard.2007.071522; Goldenberg et al, JAMA 2004;292:2388-2395; Clauw et al, Best Pract Res Clin Rheumatol 2003;17:685-701; Arnold et al, Arthritis Rheum 2007;56:1336-1344

Nonpharmacological

• Aerobic exercise• Cognitive behavioral therapy• Patient education• Strength training• Acupuncture* • Biofeedback* • Balneotherapy*• Hypnotherapy*

Pharmacological• Analgesics*• Analgesic antiepileptics• Antidepressants• Other

*Limited evidence for efficacy exists

Presenter

Presentation Notes

A multidisciplinary approach (education, certain medications, exercise, cognitive therapy) that utilizes both pharmacological and nonpharmacological therapies has been shown to be effective in the management of Fibromyalgia.1 Multidisciplinary treatment has been shown to improve patient outcomes �in Fibromyalgia1 Several pharmacological agents have published data or ongoing studies �in Fibromyalgia1 Data also support the use of nonpharmacological approaches for the management of Fibromyalgia. Nonpharmacological therapeutic options include: aerobic exercise, cognitive behavioral therapy, patient education, strength training, acupuncture, biofeedback, balneotherapy, and hypnotherapy1 Intensive patient education about Fibromyalgia has been shown to improve pain, sleep, fatigue, and quality of life in patients with Fibromyalgia1 The evidence-based guidelines recommended by Goldenberg et al were based on a search of all human trials (randomized controlled trials and meta-analyses of randomized controlled trials) of Fibromyalgia using Cochrane Collaboration Reviews (1993-2004), MEDLINE (1966-2004), CINAHL (1982-2004), EMBASE (1988-2004), PubMed (1966-2004), Healthstar (1975-2000), Current Contents (2000-2004), Web of Science (1980-2004), PsychInfo (1887-2004), and Science Citation Indexes (1996-2004)1

Treatments used by primary care physicians

• Amitriptyline• Milnacipran• Fluoxetine• Nortriptyline• Pregabalin• Tramadol• Moclobemide• Cyclobenzaprine• Duloxetine• Zolpidem

SNRI = selective norepinephrine reuptake inhibitor.Please see Full Prescribing Information and Medication Guide available at at this presentation.Cymbalta®, SavellaTM, and LYRICA® are the trademarks of Lilly LLC, Forest Pharmaceuticals Inc, and Pfizer Inc, respectively.

Garcia-Campayo et al. Arthritis Res Ther 2008;10:1-15.

Presenter

Presentation Notes

A recent systematic review and meta-analysis of all randomized controlled trials (RCTs), from 1966 to 2006, of pharmacological treatments that are available in standard primary care settings showed these medications to be most likely associated with primary care physicians. Most of these agents are NOT approved for the treatment of fibromyalgia Only LYRICA® (pregabalin) capsules CV, Cymbalta® (duloxetine), and SavellaTM (milnacipran) are indicated for the treatment of pain associated with fibromyalgia Reference: Garcia-Campayo J, Magdalena J, Magallón R, Fernández-García E. A meta-analysis of the efficacy of fibromyalgia treatment according to level of care. Arthritis Res Ther. 2008;10:1-15.

METHYCOBAL

An active form of cobalamin

Participates in transmethylation

Improves synthesis of proteins, nucleicacids and phospholipids which are needed in the repair of damaged nerves.

BENEFITS ALL TYPES OF PERIPHERAL NEUROPATHIES

Nerve cell

Myelin sheath AxonMuscle

SEGMENTAL DEMYELINATIONe.g :Diabetic neuropathyAlcoholic neuropathyUremic neuropathyGuillain-Barre syndrome

WALLERIAN DEGENERATIONe.g :Spondylosis deformansHernia of intervartebral discCarpal tunnel syndromeFacial palsyGlaucomatous optic atrophy

AXONAL DEGENERATIONe.g :Drug-induced neuropathies[Vincristine, isonicotinicacid hydrazide (INH), etc]Herpes zoster

Direction of degeneration

Direction of degeneration

Modified MELIALA, 2006

METHYCOBAL’S EFFECT ON ECTOPIC FIRING OF DORSAL ROOT GANGLION (DOG MODEL)

Atsuta et.al Methycobal Forum 1993; 101-103

Methycobal was added to the CSF solution

(to make a concentration of 50 μg.ml) bathing

the dorsal root ganglia During anoxia-induced

ectopic firing. The firing was suppressed

and the frequency (spike/sec.) dropped

significantly after the additionof Methycobal

Metilkobalamin: Kesimpulan • Metilkobalamin adalah bentuk aktif Vit B12, siap

digunakan tubuh dalam reaksi metilasi homosistein membentuk metionin

• Reaksi metilasi berperan pada pembentukan DNA, protein yang penting untuk saraf, pembentukan mielin dan transpor aksonal

• Metilkobalamin berperan pada regenerasi saraf yang mengalami kerusakan, misalnya pada, nyeri neuropatik, neuralgia nervus kranialis, peripheral nerve injury, vertigo dan tinitus dengan mengurangi ectopic discharge

Kesimpulan • Metilkobalamin berperan pada penurunan kadar

homosistein mengurangi kerusakan saraf akibat terbentuknya reactive oxygen species

• Berperan pada proteksi neuron SSP akibat glutamate-induced neurotoxicity proteksi neuron pada stroke, cedera serebral, Alzheimer, Parkinson, Hipoglikemia dan Status epileptikus

• Secara umum sediaan oral maupun injeksi cukup aman dengan kejadian efek samping yang kecil

ANALGESIC MEDICATIONS ON INFLAMATORY PAIN

PRIMARY ANALGESICS• Acetaminophen• Prostaglandin synthesis inhibitors

– Salicylates– Traditonal NSAIDs– COX-2-selective NSAIDs (coxibs)

• Tramadol• Opioids

– Traditional– Mixed

ADJUVANT MEDICATIONS• Antidepressants• Anticonvulsants• Local anesthetics• Muscle Relaxant• Miscellaneous agents

Clinical Experience

• NSAID dipergunakan > 40 th sampai sekarang masih terbaik

• Khusus : Nyeri dengan inflamasi

Dionne et al, 2010In Mogill J (Ed) Pain 2010, Clinical Pharmacology et Nonsteroidal Antiinflammatory Drugs, 217-223

Nama Obat Dosis JadwalAspirin 325-1000 mg 4-6 jam sekali

Kalium Diklofenak 50-200 mg 8 jam sekaliNatrium diklofenak 50 mg 8 jam sekali

Ibuprofen 200-800 mg 4-8 jam sekaliIndometasin 25-50 mg 8-12 jam sekaliKetoprofen 25-75 mg 6-12 jam sekali

Asam mefenamat 250 mg 6 jam sekaliNaproxen 250-500 mg 12 jam sekali

Piroksikam 10-20 mg 12-24 jam sekaliTenoksikam 20-40 mg 24 jam sekaliMeloksikam 75 mg 24 jam sekaliCelecoxib 100 mg 12 jam sekaliNimesulfid 100 mg 12 jam sekaliKetolorak 10-30 mg 4-6 jam sekali

Asetaminofen 500 mg 6-8 jam sekaliTramadol 50-100 mg 8 jam sekali

Analgetik Yang Paling Sering Digunakan

Mekanisme Proteksi Nyeri spasme otot

I

γα

II-IV

III-IV

Ia

Joint receptor (nociceptor)

Joint dysfunctionor pain

Nociceptor

Muscle painA

B

Muscle spindle

γ-Motoaxon

α-Motoaxon

Descending influencesCSpinothalamic

tract

I

γα

Eperison

PAINNO PAINNO PAIN

Eperisone HCl (Myonal ®)

• Golongan antispasmodik, banyak dipakai nuntuk efek muscle relaxant

• Insidensi sedasi kecil, dibanding obat lain yang segolongan– Mempermudah aplikasi klinis, untuk pasien

yang membutuhkan terapi tanpa mempengaruhi alertness

• Efek samping yang timbul biasanya jarang terjadi

SITES OF ACTION OF EPERISONE IN THE VICIOUS CYCLE OF HYPERTONIA

Contraction of Muscles

Ischemia

Pain Stimuli

Pain

Ischemia

Pain

Isch

emia

Pain

Relaxes hypertonia

Inhibit pain reflex

Improves circulation

EPERISONE HCL


Difficulty in Walking

Difficulty in Going Upand Down Stairs

Lumbago

Stiff Shoulders

Cervical Pain

Tinnitus

HeadacheDizziness

Stiffness

Rigidity

77.577.5

65.4

71.9

80.7

71.5

55.2

53.9

68.9

66.4

IMPROVEMENT RATES WITH EPERISONE


Myonal: Kesimpulan

• Relaksasi otot skelet yang mengalami hipertonus

• Memperbaiki aliran darah intramuskuler• Mengurangi sensitivitas muscle spindle

melalui neuron motorik• Vasodilatasi dan augmentasi aliran darah• Aksi analgesik dan inhibisi refleks nyeri di

medula spinalis

SimpulanPemahaman mekanisme nyeri

sangat bermanfaat dalam penatalaksanaan nyeri

SEMOGA TIDAK NYERISALAM

Documents

Management of Different Types of Pain Prof Lucas