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Title: Perubahan Kadar TNF-α, Interleukin-1, Interleukin-6 Serum Setelah Pemberian Amitriptilin atau Deksketoprofen dan Korelasinya dengan Tingkat Intensitas Nyeri pada Penderita Tension-Type Headache Kronik
Authors: Rambe, Aldy Safruddin
Advisors: Sjahrir, Hasan
Machfoed, Moh. Hasan
Nasution, Darulkutni
Issue Date: 25-May-2016
Abstract: Aim : Experimental studies suggest that central sensititization plays important role in pathophysiology of chronic pain and chronic tension-type headache (CTTH). Studies on pro-inflammatory cytokines during headache attack showed elevated interleukin (IL)-1β and tumor necrosis factor (TNF)-α levels in the cerebrospinal fluid, but not in the serum. This study was aimed to see the serum levels of TNF-α, IL-1, IL-6 in patients with CTTH and its correlation with pain intensity. Methodology : This experimental study was conducted at the Adam Malik Hospital and Bukit Barisan II Army Hospital from January 2013 to June 2014 after approved by the Ethics Committee for Health Research University of North Sumatera School of Medicine. Diagnosis of CTTH was based on the diagnostic criteria as stated in the ICH X. The subjects were recruited consecutively from study population. .Subjects underwent assessment of pain intensity by using the Numeric Rating Scale ( NRS ) for pain and venous blood was taken to measure serum levels of TNF-α , IL-1, and IL-6. Then, subjects were divided into 2 groups. The first group was given Amitriptilin 25 mg once daily and the second group was given Dexketoprofen 50 mg once daily, for 10 consecutive days. One day after the last dosage, pain intensity was reassessed and venous blood was taken for the second time to measure the serum levels of TNF-α , IL-1, and IL-6. Results : Forty six CTTH patients participated in this study, most were female (82.6%), in the age group 0f 30-60 years old (78.3%), married (86.9%), Batak Toba tribe (56.5%), work as government employee (52.2%), senior high school graduated (52.2%), and without any history of hypertension (78.3%), diabetes mellitus (95.6%), and not smoking (95.6%). There was no significant difference among these demographic factors (p>0.05). Before drug administration, there was no significant correlation between NRS score and TNF-α (p=0.849), IL-1 (p=0.794) or IL-6 serum levels (p=0.347) In the Amitriptyline group, there was a significant lowering of NRS scores from baseline(p=0.001), but not for TNF-α (p=0.057), IL-1 (p=0.785) , nor IL-6 serum levels (p=0.862). There was a negative very weak and non significant correlation between NRS scores and TNF-α (R=-0.178; p=0.415 ) and IL-1 serum levels (R=- 0.111 ; p=0.615) and a negative weak and non significant correlation between NRS scores and IL-6 serum levels (R= -0.364 ; p=0.088). In the Dexketoprofen group, there was also a significant lowering of NRS scores from baseline (p=0.001), but not for TNF-α (p=0.956), IL-1 (p=0.432), nor IL-6 serum levels (p=0.819). There was a negative very weak and non significant correlation between NRS scores and TNF-α (R=-0.266;p=0.219) and IL-6 serum levels (R= -0.019 ; p=0.932), and a positive weak correlation between NRS scores and IL-1 serum levels (R= 0.221 ; p=0.311). After drugs administration, there was a significant difference between these two groups on IL-6 serum levels (p=0.012), but not significant for TNF-α (p=0.052) and IL-1 serum levels (p=0.705), nor NRS scores (p=0.755). In the Amitriptyine group, after taking this drug There was a negative very weak non significant correlation between NRS scores and TNF-α (R=-0.178 ; p=0.415), and IL-1 serum levels (R=- 0.111 ; p=0.615), and a negative weak non significant correlation between NRS scores and IL-6 serum levels (R= -0.364 ; p=0.088). In the Dexketoprofen group, after taking this drug there was a negative weak non significant correlation between NRS scores and TNF-α (R=-0.266;p=0.219), and IL-6 serum levels (R= -0.019 ;p=0.932), and a positive weak non significant correlation between NRS scores and IL-1 serum levels (R=0.221 ; p=0.311). Conclusions : Both drugs were found effective in reducing pain intensity in CTTH patients. At baseline, there was a non significant correlation between NRS scores and TNF-α, IL-1 or IL-6 serum levels. In the Amitriptyline group, there was no significant differences from baseline for TNF-α (p=0.057), IL-1 (p=0.785) and IL-6 serum levels (p=0.862). There was also no significant differences from baseline for TNF-α (p=0.956), IL-1 (p=0.432) and IL-6 serum levels (p=0.819) in the Dexketoprofen group . After Amitriptyline or Dexketoprofen administration, NRS scores had non significant correlations with TNF-α, IL-1 and IL-6 serum levels. There was a larger and significant (p=0.012) decrement IL-6 serum levels in Amitriptyline group compare with the Dexketoprofen group, but no significant differences for NRS scores, TNF-α and IL-1 serum levels.
Abstract (other language): Pendahuluan : Penelitian eksperimental menunjukkan bahwa sensitiasi sentral berperan penting dalam patofisiologi nyeri kronik dan TTH kronik. Penelitian terhadap sitokin pro-inflamasi, interleukin-1 β (IL)-1β dan tumor necrosis factor (TNF)-α menunjukkan adanya peningkatan kadarnya dalan cairan serebrospinalis selama serangan nyeri kepala, tetapi tidak di dalam serum. Tujuan : Penelitian ini bertujuan untuk meneliti kadar TNF- α, Il-1 dan IL-6 dalam serum pada penderita TTH kronik dan korelasinya dengan intensitas nyeri. Metode : Penelitian eksperimental ini dilaksanakan di RSUP H. Adam Malik, Rumkitdam II BB dan RS Haji Medan dari Januari 2013 sampai Juni 2014 setelah mendapat persetujuan dari Komite Etik Untuk Penelitian Bidang Kesehatan FK-USU. Diagnosis TTH kronik berdasarkan kriteria dari ICH X. Subjek diambil dari populasi penelitian secara konsekutif. Setelah dinilai intensitas nyeri dengan menggunakan NRS dan diambil darah vena untuk pengukuran kadar TNF- α, Il-1 dan IL-6, subjek dibagi menjadi 2 kelompok. Kelompok pertama diberi Amitriptilin 1x25 mg dan kelompok kedua diberi Deksketoprofen 1x50 mg, selama 10 hari. Penliaian intensitas nyeri dan pengukuran kadar sitokin ini dilakukan kembali 1 hari setelah dosis obat terakhir. Selanjutnya data dianalisa untuk melihat perubahan kadar TNF- α, Il-1 dan IL-6 serum sebelum dan sesudah pemberian obat serta korelasinya dengan intensitas nyeri. Hasil : Empat puluh enam penderita TTH kronik berpartisipasi dalam penelitian ini, sebagian besar perempuan (82,6%). Mayoritas subjek (78,3%) berada pada kelompok usia 30-60 tahun. Sebagian besar subjek sudah menikah (86,9%), suku Batak Toba (56,5%), bekerja sebagai PNS (52,2%), pendidikan SMA (52,2% , tidak memiliki riwayat menderita hipertensi (78,3%), tidak menderita diabetes mellitus (95,6%) dan tidak merokok (95,6%). Tidak terdapat perbedaan yang signifikan dari faktor-faktor demografis tersebut di antara kedua kelompok (p>0,05). Nilai rerata kadar serum TNF- α 1,81528 pg/ml (SD±0,890686), IL-1 0,20226 pg/ml (SD±0,193930), dan IL-6 1,45089 pg/ml (SD±1,189502). Sebelum perlakuan, tidak dijumpai korelasi yang signifikan antara skor NRS dengan kadar serum TNF-α (p=0,849), IL-1 (p=0,794) maupun IL-6 (p=0,347). Pada kelompok Amitriptilin dijumpai perbedaan yang signifikan antara skor NRS (p=0,001) sebelum dan setelah minum obat, tetapi tidak signifikan pada kadar serum TNF-α (p=0,057), IL-1 (p=0,785) maupun IL-6 (p=0,862). Pada kelompok Deksketoprofen dijumpai perbedaan yang signifikan antara skor NRS (p=0,001) sebelum dan setelah minum obat, tetapi tidak signifikan pada kadar serum TNF-α (p=0,956), IL-1 (p=0,432) maupun IL-6 (p=0,819). Setelah meminum obat, dijumpai perbedaan yang bermakna pada kadar IL-6 (p=0,012) di antara kedua kelompok, tetapi perbedaan ini tidak signifikan untuk kadar serum TNF-α (p=0,052), IL-1 (p=0,705) maupun skor NRS (p=0,755). Setelah meminum Amitriptilin, didapati hubungan negatif sangat lemah yang tidak signifikan antara skor NRS dengan kadar TNF-α (R=-0,178; p=0,415 ), juga didapati hubungan negatif sangat lemah dan tidak signifikan (R=- 0,111 ; p=0,615) antara skor NRS dengan kadar IL-1, serta hubungan negatif lemah yang tidak signifikan (R= -0,364 ; p=0,088) dengan kadar IL-6. Setelah meminum Deksketoprofen, didapati hubungan negatif sangat lemah yang tidak signifikan antara skor NRS dengan kadar TNF-α (R=-0,266; p=0,219 ), juga didapati hubungan positif lemah dan tidak signifikan (R= 0,221 ; p=0,311) antara skor NRS dengan kadar IL-1, serta hubungan negatif sangat lemah yang tidak signifikan (R= -0,019 ; p=0,932) dengan kadar IL-6. Kesimpulan : Amitriptilin maupun Deksketoprofen efektif dalam menurunkan intensitas nyeri pada penderita TTH kronis. Sebelum diberikan obat, didapati hubungan yang tidak signifikan antara intensitas nyeri dengan kadar TNF-α, IL-1 maupun IL-6 serum. Pada kelompok Amitriptilin, sebelum dan setelah pemberian obat penurunan kadar rerata serum TNF-α (p=0,057), IL-1 (p=0,785) dan IL-6 serum (p=0,862) tidak signifikan. Pada kelompok Deksketoprofen, tidak dijumpai penurunan yang signifikan antara kadar TNF-α serum (p=0,956), IL-1 (p=0,432) maupun IL-6 (p=0,819) sebelum dan sesudah pemberian obat. Setelah meminum Amitriptilin, intensitas nyeri memiliki korelasi yang tidak signifikan dengan kadar TNF-α, IL-1 dan IL-6 serum. Setelah meminum Deksketoprofen, intensitas nyeri memiliki korelasi yang tidak signifikan dengan kadar TNF-α , IL-1 dan IL-6 serum. Didapati penurunan yang lebih besar dan signifikan (p=0,012) kadar IL-6 serum pada kelompok Amitriptilin dibanding kelompok Deksketoprofen. Hal serupa tidak dijumpai pada parameter intensitas nyeri, kadar TNF-α dan IL-1 serum.
Keywords: chronic tension-type headache
cytokines
IL-1
IL-6
TNF-α
URI: http://repository.usu.ac.id/handle/123456789/59247
Appears in Collections:PD - Pendidikan Doktor

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Chapter I.pdfChapter I571.88 kBAdobe PDFView/Open
Chapter II.pdfChapter II1.98 MBAdobe PDFView/Open
Chapter III-VI.pdfChapter III-VI1.19 MBAdobe PDFView/Open
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Appendix.pdfAppendix4.68 MBAdobe PDFView/Open
 

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