FINEST PRESENTASI PROF DESSY .pptx

NEW UPDATE ON NEUROPATHIC PAIN : EMERGING CONCEPT IN COMBINATION OF CITICOLINE AND PREGABALIN Prof. Dr. dr. Dessy R Emril, Sp.S(K) Pain and Headache Division Neurology Department, Medical Faculty Universitas Syiah Kuala  INTRODUCTION Pain is...

NEW UPDATE ON NEUROPATHIC PAIN : EMERGING CONCEPT IN COMBINATION OF CITICOLINE AND PREGABALIN Prof. Dr. dr. Dessy R Emril, Sp.S(K) Pain and Headache Division Neurology Department, Medical Faculty Universitas Syiah Kuala  INTRODUCTION Pain is an unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage IASP defines neuropathic pain as pain caused by a lesion or disease of the somatosensory nervous system  NEUROPATHIC PAIN DEFINITION “Neuropathic pain is described as burning, painful, cold or electric “Pain initiated or caused by a primary shocks and may be associated with lesion or dysfunction of the nervous tingling, pins and needles, system” (IASP) numbness or itching” “Pain arising as a direct consequence of a lesion or disease affecting the somato-sensory system” (NeupSIG– IASP 2010)  PREVALENCE OF NEUROPATHIC PAIN IN INDONESIA The prevalence of neuropathic pain in Indonesia is 1.2% of the total population Prevalence of neuropathic pain was higher in male than in female (62.1% vs 37.9%) 62% are chronic pain with moderate-severe complaints Chronic Low Back Pain (37%), Post-Operative Pain (34%) and Diabetic Neuropathy (26%) are the MOST CASES 2.8 million people in Indonesia experience Neuropathic Pain Neurona, Majalah Kedokteran Neuro-Sains. PB PERDOSSI 2015 and Neurology Asia 2015 PATOPHISIOLOGY Neuropathic pain results from diverse pathobiological mechanisms. Among these diverse mechanism, two of them were predominantly observed: peripheral and central sensitization.  Injury NEUROPATHIC PAIN Peripheral SupraSpinal Mechanism Spinal Mechanism Mechanism Nociceptor sensitization Glu - regulation (SP, CGRP, Local Udema) Glial activation- Sensory denervation- Proinflammatory NGF/sprouting cytokines Expression of ion channel Disinhibition Phenotypic switch Opioid-R SP, CGRP Expanded SMP receptive fields ↓ stimulation Provoke ectopic Trigger central ↑ exitability Hyper- threshold discharge sensitization polarization NERVE REGENERATION POST INJURY  OPTIMAL RGENERATION IS A MUST TO PREVENT NEUROPHATIC PAIN INTERVENTION FOR NP Axonal Injury Regeneration is not Optimal optimal regeneration INTREVENTION (promote nerve regeneration) Complex cascade INTERVENTION NEUROMA (many (Antineurophatic Prevent NP SPROUTING mechanisms) pain)  PHARMACOLOGICAL CHARACTERISTICS OF CITICOLINE AND PREGABALIN PHARMACOLOGICAL CHARACTERISTIC OF PREGABALIN Pregabalin's pharmacologic effects are primarily through modulation of voltage-gated calcium channels in the CNS Pregabalin enhances the inhibitory effects of GABAergic neurotransmission, which in turn dampens excitatory synaptic and modulates the pain signaling cascade.  3 ROLES OF PREGABALIN: Anxiolytic, Analgesic, Anticonvulsant Pregabalin: reduce excessive neuronal activity in 3 areas of the pain pathway (Anxiolytic, Analgesic, Anticonvulsant) by: 2-4  Reducing Hyper-excitation in Ascending pain pathways.  Reducing Dysregulation in areas of the brain associated with pain perception & modulation.  Restoring inhibitory Descending pain pathways to normal physiological state.  THE NEW ROLE OF CITICOLINE Currently, research found the role of citicoline on peripheral nerve injury that proven effective in helping the regeneration of axons after injury All this time, citicoline has There was no previous been used widely as the research that aimed to find traetment of cerebral the effectiveness of citicoline injuries (stroke, head in preventing neuropathic trauma and cognitive pain (through the mechanism impairment) of optimal axon regeneration) NEW ROLE: CITICOLINE to prevent neuropathic pain CITICOLINE ROLE IN AXONAL REGENERATION AND PREVENTING NUERIPHATIC PAIN  NEUROPROTECTIVE, NEUROGENERATIVE, NEUROPLASICITY EFFECTS OF CITICOLINE Citicoline, also known as cytidine diphosphate-choline or CDP- choline, is a natural compound involved in phospholipid synthesis and neuronal membrane repair. The neuroprotective and neuroregenerative effects of Citicoline make it a drug that could potentially enhance recovery after neurologic disorders  COMPLEMENTARY EFFECTS BETWEEN PREGABALIN AND CITICOLINE According to Leksiri (2020) Analgesic drugs in combination can achieve better efficacy with fewer side effects compared to monotherapy. Pregabalin has been found to be useful in the management of CPSP Citicoline, on the other hand, has and neuropathic pain with shown good effects in motor improvement in secondary outcomes functional recovery and such as improvement in sleep prevention of neuropathic pain in disturbance and decrease in anxiety, animal models with sciatic nerve with its effect on reducing injury postsynaptic currents in the cornu dorsalis of the spinal cord.  EFFICACY OF PREGABALIN AND CITICOLINE IN NEUROPATHIC PAIN The neuroprotective ,neuroregenerative, and Neuroplascitity effects of Citicoline make it a drug that could potentially enhance recovery after nerve injuries CITICOLINE NEW ROLE : CITICOLINE to prevent neurophatic Pain  EFFICACY OF PREGABALIN AND CITICOLINE IN NEUROPATHIC PAIN Reduce Pain PREGABALIN Hypersensitivity Pregabalin To Prevent Neurophatic Inhibits The Release Pain Of Neurotransmitters Decreases Neuronal Involved In Pain Hyperexcitability Physiology  sesudah perlakuan EFFICACY OF CITICOLINE Tabel 4.2 menunjukkan perbandingan antar variabel pada kelompok I dan IN THE MANAGEMENT OFnormalCTS Data yang terdistribusi diuji menggunakan Uji T dependen, sedangk data yang terdistribusi tidak normal diuji menggunakan Uji Wilcoxon. Tabel 4.2. Hasil uji perbandingan rerata skor NRS dan KHS kelompok I dan II Variabel Sebelum Setelah p-value Rerata ± SD Rerata ± SD Kelompok 1 NRS 7,00 ± 1,96 1,23 ± 0,59 0,001** SNAP KHS kanan 31,48 ± 17,49 60,72 ± 12,01 0,001** KHS kiri 21,91 ± 6,09 61,55 ± 6,85 0,000* CMAP KHS kanan 54,83 ± 4,05 62,26 ± 10,37 0,013* KHS kiri 54,80 ± 4,93 60,57 ± 7,14 0,001** Kelompok II NRS 7,23 ± 1,53 2,00 ± 0,82 0,001** SNAP KHS kanan 27,78 ± 12,02 55,03 ± 6,79 0,001** KHS kiri 24,50 ± 6,49 54,74 ± 8,87 0,000* CMAP KHS kanan 48,40 ± 10,63 58,09 ± 10,93 0,001** KHS kiri 53,23 ± 7,49 56,52 ± 7,51 0,055** Keterangan: *Uji T dependen **Uji Wilcoxon Tabel di atas menunjukkan perbedaan yang signifikan rerata variabel pa EFICACY OF CITICOLINE IN THE MANAGEMENT OF PDN CITICOLINE prevent neuropathic pain after nerve injury Daily dose of citicoline is 2000 mg (2x100mg/day) CITICIOLINE may effective in treatment of NP : Diabetic painful neuropathy Radikulopathy (LBP, Neck pain) Traumatic nerve injury Nerve entrapment synd (CTS, TTS, Cubital TS) Other cases of NP CITICOLINE AND PERIPHERAL NERVE INJURY PNS : Have the regenaration Improvement after injury by the role of Neuroplasticity Neuroproctective Neurogenerative CITICOLINE AND THE CNS INJURY CNS : No regenaration Improvement after injury by the role of Neuroplasticity  Administration of cytidine 5'- diphosphocoline can help the regeneration of axons after injury Administration of cytidine 5'- diphosphocoline post-injury can fix or CONCLUSION improve motoric function Administration of cytidine 5'- diphosphocoline may decrease or inhibit the expression of the sodium channel (VGSC) by prevent or reduce the formation of neuroma Administration of cytidine 5'- diphosphocoline can prevent neuropathic pain behavior  CONCLUSION Pregabalin and Citicoline combination therapy may be considered as one of the potential therapeutic strategies for Neurophatic Pain cases, with the support of preclinical and clinical studies showing a possible synergistic effect on pain improvement and functional recovery. Studies that address the mechanism of action of both Pregabalin and Citicoline suggest complementary actions of Pregabalin and Citicoline on excitatory neurotransmission, neuroprotection, and neuroplasticity. THANKS YOU