SCN1A exon 26 variants in epilepsy and migraine patients

Epilepsy and migraine are common neurological diseases in many populations. Mutation of the voltage gated natrium channel Nav1.1 (SCN1A) are important causes of different genetic epilepsies and can also cause familial hemiplegic migraine (FHM-III). This study aimed to identify SCN1A gene variation in patients with epilepsy and common migraine. Gene variation analysis of exon 26 of the SCN1A gene was carried out in 33 patients with epilepsy, 33 patients with migraine and 30 control individuals from Neurology Polyclinic at Dr. Zainoel Abidin General Hospital, Banda Aceh. The PCR and direct sequencing methods were performed in this study. SCN1A gene variations were identified in two epilepsy patients. These gene variations located at exon 26 were four silent mutations in patient E27 at position A4440T (Leu1480Leu), T4443C (Leu1481Leu), A5046G (Leu1682Leu) and C5121T (Asp1707Asp). One silent mutation in patient E30 at position G5505A (Glu1835Glu). None of these gene variations were identified in controls and patients with common migraine in this study. This study has identified 5 genetic variations of SCN1A in patients with epilepsy but not in common migraine. The mechanism and relationship between these variants and epilepsy need to be clarified

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

Current understanding of the mixed pain concept: a brief narrative review

Despite having been referenced in the literature for over a decade, the term “mixed pain” has never been formally defined. The strict binary classification of pain as being either purely neuropathic or nociceptive once left a good proportion of patients unclassified; even the recent adoption of “nociplastic pain” in the IASP Terminology leaves out patients who present clinically with a substantial overlap of nociceptive and neuropathic symptoms. For these patients, the term “mixed pain” is increasingly recognized and accepted by clinicians. Thus, an independent group of international multidisciplinary clinicians convened a series of informal discussions to consolidate knowledge and articulate all that is known (or, more accurately, thought to be known) and all that is not known about mixed pain. To inform the group’s discussions, a Medline search for the Medical Subject Heading “mixed pain” was performed via PubMed. The search strategy encompassed clinical trial articles and reviews from January 1990 to the present. Clinically relevant articles were selected and reviewed. This paper summarizes the group’s consensus on several key aspects of the mixed pain concept, to serve as a foundation for future attempts at generating a mechanistic and/or clinical definition of mixed pain. A definition would have important implications for the development of recommendations or guidelines for diagnosis and treatment of mixed pain. © 2019, © 2019 Informa UK Limited, trading as Taylor and Francis Group