RESPON REGENERASI AKSONAL TERHADAP PEMBERIAN CYTIDINE 5�-DIPHOSPHOCHOLINE GUNA MENCEGAH NYERI NEUROPATIK: Kajian Eksperimental in vivo Cedera Nervus Ischiadicus pada Tikus Wistar

Background. Cytidine 5'-diphosphocoline (citicoline) has been shown to have beneficial effects on the central nervous system injury as well as peripheral nerve injury. This study aimed to examine the effect of citicoline in preventing neuropathic pain in rat model of sciatic nerve crush injury. Methods: Thirty-six rats were divided into one sham operation group and four injury froup. The injury group consisted of saline group (n=7), while the treatment group consisted of intraperitoneal citicoline+50 mg /ml of 0.4 cc local citicoline (citicoline i.p.+ 50, n = 7), citicoline intraperitoneally + 125 mg/ml of 0.4 cc of local citicoline (citicolineip+125, n= 8), citicoline intraperitoneally 50 mg / 100 g BB (citicoline ip, n= 8). The sciatic crush area of saline group wrapped with gelatin sponge soaked with 0.4 ml of 0.9% saline solution while sciatic crush area in treatment group wrapped with gelatin sponge soaked with citicoline in appropriate dose and given of citicoline intraperitoneally five minutes after the crush process. Assessment of motor function by measuring the sciatic fungtional Index (SFI) and the Test of extensor postural thrust (EPT) as well ass neuropathic pain behavior by Von frey filament test performed at the fourth and eighth week. Transverse section of right n. ischiadicus 10 mm distal to the injury painted with OsO4 done after the week eighth. Rating Nav 1.7 expression semiquantitatively after Rabit polyclonal antibody supplied with Nav 1.7/SCNA9A also performed after the week eighth. Result. At week 4, the positive neuropathic pain found more in the group of rats that were given only citicolineii.p. (75%) and saline (57.1%) compared to two groups that were given citicoline local + ip (14.3% and 25%). However, statistically there was no difference between the groups (p> 0.05). No positive neuropathic pain behavior found in the sham operation group both at week 4 and week 8. At week 8, the positive neuropathic pain remains found in 57.1% saline group rats. Neuropathic pain behavior no longer found (0%) in all mice given citicoline (p<0.05). EPT test week 8 showed the mean motor deficit group were given citicoline were lower than the motor deficit in the saline group p <0:01). There is no difference in the mean SFI scores between groups at weeks 4 and 8. The histomorfology finding showed more small fasciculus or neuroma (θ<20μm) in the saline group, while the citicoline group showed fasciculus that have an almost similar figure with the group of sham operation (θ> 40μm). The mean diameter of the nerve fibers in the saline group was 9.61± 1.17μm, citicoline ip + 50 group (12.9 ± 1.88 m), citicoline ip + 125 group (11:59 ± 1.68 m), Citicoline ip group (11.84 ± 0.91 m), sham operation group (17.64 ± 4.83 μm), p>0.05. So is the case with the mean diameter of axons saline group (4.94 ± 0.62 μm) which showed no significant difference with citicoline group (p> 0.05), except with citicoline ip + 50 which has a mean diameter of axon 6.91±1.56 μm (p= 0.04). Thick myelin and axon density in saline group also showed no significant difference between citicoline group and saline group (p> 0.05), except for axon density of citicoline ip + 50 group (43.28 ±9.77/ mm2), p = 0.037. The result of semi quantitative test of the expression of Nav 1.7 in the proximal injury showed expression scores of 2.42 ± 0.06 (saline group) which is higher than the other groups, p <0.001, as also seen in the expression of Nav 1.7 scores on the medial segment (p <0.001). There is no significant difference in the expression of Nav 1.7 scores in the distal segment (p> 0.05). Conclusion. Administration of cytidine 5'- diphosphocoline (citicoline) locally and intraperitoneally after crush injury of n. ischiadicus inhibits neuropathic pain behavior, improve motor function, reduced neuroma formation and expression of Nav 1.7 at week 8 Keywords: citicoline, sciatic nerve injury, nerve regeneration, neuropathic pai

Cytidine 5&rsquo;-diphosphocholine administration prevents peripheral neuropathic pain after sciatic nerve crush injury in rats

Dessy R Emril,1 Samekto Wibowo,2 Lucas Meliala,2 Rina Susilowati3 1Department of Neurology, Faculty of Medicine, Syiah Kuala University, Banda Aceh, 2Department of Neurology, 3Department of Histology and Cell Biology, Faculty of Medicine, Universitas Gadjah Mada, Yogyakarta, IndonesiaBackground: Cytidine 5&rsquo;-diphosphocholine (citicoline) has been shown to have beneficial effects in central nervous system injury as well as in motoric functional recovery after peripheral nerve injury. This study aimed to examine the effect of citicoline on prevention of neuropathic pain in a rat model of sciatic nerve crush injury.Methods: Forty experimental rats were divided into four groups. In three groups, the right sciatic nerves were crushed in the mid-thigh region, and a gelatin sponge moistened with 0.4 or 0.8 mL of 100 &micro;mol/L citicoline, or saline 0.4 mL in the control group, was applied. The fourth group of rats was sham-operated, ie the sciatic nerve was exposed with no crush. Functional assessments were performed 4 weeks after crush injury. von Frey filaments (100 g threshold) were used to assess neuropathic pain. In addition, the sciatic functional index and extensor postural thrust (EPT) tests were used to assess motoric function.Results: The crush/citicoline 0.4 mL group had a lower percentage of pain (23.53%, n=17) compared with the crush/saline group (53.33%, n=15, P&lt;0.005). The crush/citicoline 0.4 mL group also showed better motoric recovery, as seen in stronger EPT results (P&lt;0.001). However, the sciatic functional index analysis did not show significant differences between groups (P=0.35). The crush/citicoline 0.8 mL group showed a higher percentage of pain (66.67%, n=18) and less EPT recovery. These results may be explained by more severe nerve injury due to compression with a larger administered volume.Conclusion: In situ administration of 0.4 mL of 100 &mu;mol/L citicoline prevents the occurrence of neuropathic pain and induces motoric recovery, evaluated by EPT test, 4 weeks after sciatic nerve injury.Keywords: nerve injury, nerve regeneration, neuropathic pai