Administration Of Phenytoin Research Articles

Improving effect of mild foot electrical stimulation on pentylenetetrazole-induced impairment of learning and memory

Epilepsy is a common neurological disorder that affects learning and memory. Recently it has been shown that mild foot electrical stimulation (MFES) can increase learning and memory in normal rats. Pentylenetetrazole (PTZ) kindling is a model of human epilepsy. As with human epilepsy, PTZ kindling impairs learning and memory in rats. The purpose of this study was to investigate the effect MFES on kindling-induced learning and memory deficits in rats. Forty-nine male Wistar rats weighting 200 to 250 g were divided into the following seven groups: PTZ only, phenytoin only, MFES only, PTZ plus phenytoin, PTZ plus MFES, phenytoin plus MFES, and saline (control), with the treatments administered for 26 days. Forty-eight hours after the last injection, the animals performed the Morris water maze (MWM) task, and spatial learning and memory were measured. The results indicated that although chronic administration of phenytoin inhibited the development of PTZ kindling, it did not exert a protective effect against kindling-induced spatial learning and memory impairment in rats. On the other hand, pretreatment of PTZ-kindled animals with MFES significantly improved spatial working and reference memory. The results point to potential novel beneficial effects of MFES on learning and memory impairment induced by PTZ kindling in rats.

Paroxysmal Ataxia and Dysarthria in a Patient with Demyelinating Disease

Paroxysmal dysarthria and ataxia is characterized by abrupt onset of dysarthria and ataxia of unilateral limbs for seconds. We present a 45-year-old female patient with paroxysmal symptoms of dysarthria, right-sided ataxia, and a persistent symptom of upbeating nystagmus. Her brain fluid attenuated inversion recovery (FLAIR) magnetic resonance imaging indicated potential diagnosis of demyelinating disease. The paroxysmal and persistent symptoms have recovered after phenytoin administration. Sodium channel blocker may play a role in reducing the ephaptic transmission in a demyelinated or re-myelinated lesion. Key Words: Dysarthria, Ataxia, Demyelinating disease

Short‐ and Long‐term Effects of Phenytoin Exposure on the Liver Proteome of Neonatal and Adult Mice Using SWATH‐MS Technology

Phenytoin, a drug listed on the World Health Organization's Model List of Essential Medicines, has been widely used for the treatment of seizures and several other indications. However, it has a narrow therapeutic index and some severe side effects, such as drug‐induced liver diseases. In addition, phenytoin is a well‐known inducer of several drug‐metabolizing enzymes and transporters expressed in the liver, which could lead to severe drug‐drug interactions. In the present study, a newly developed untargeted proteomics approach, sequential window acquisition of all theoretical mass spectra (SWATH), was utilized to investigate the short‐ and long‐term effects of phenytoin exposure on the liver proteome of neonatal and adult mice. A total of 1,780 protein groups were identified in the liver microsomes prepared from neonatal and adult mice. Markedly different liver proteome profiles were observed between newborn (day 5) and adult mice (day 60). Administration of phenytoin exhibited a greater short‐term impact on the liver proteome in neonates than that in adults, in which hepatic expression levels of 214 protein groups were significantly altered in newborn mice relative to 88 protein groups in adult mice at 24 h following an intraperitoneal injection of phenytoin (100 mg/kg). Furthermore, relative to vehicle control, phenytoin treatment resulted in significant changes of the expressions of 50 protein groups in the liver at age day 60 after the mice received a single intraperitoneal injection of phenytoin (100 mg/kg) at age day 5. Taken together, our study provides an insight into the effect of phenytoin treatment on the liver proteome, which might lead to a better understanding of the phenytoin‐induced hepatotoxicity and drug‐drug interactions.Support or Funding InformationThis study was supported by National Institutes of Health National Institute of General Medical Sciences [R01GM‐118367] (Xiao‐Bo Zhong).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

A Circadian Clock in the Blood-Brain Barrier Regulates Xenobiotic Efflux

Endogenous circadian rhythms are thought to modulate responses to external factors, but mechanisms that confer time-of-day differences in organismal responses to environmental insults/therapeutic treatments are poorly understood. Using a xenobiotic, we find that permeability of the Drosophila "blood"-brain barrier (BBB) is higher at night. The permeability rhythm is driven by circadian regulation of efflux and depends on a molecular clock in the perineurial glia of the BBB, although efflux transporters are restricted to subperineurial glia (SPG). We show that transmission of circadian signals across the layers requires cyclically expressed gap junctions. Specifically, during nighttime, gap junctions reduce intracellular magnesium ([Mg2+]i), apositive regulator of efflux, in SPG. Consistent withlower nighttime efflux, nighttime administration of the anti-epileptic phenytoin is more effective at treating a Drosophila seizure model. These findings identify a novel mechanism of circadian regulation and have therapeutic implications for drugs targeted to the central nervous system.

A Junctional Rhythm Caused by Administration of Intravenous Phenytoin

Introduction: We present the case of a patient with symptomatic junctional rhythm caused by administration of intravenous phenytoin. However, bradycardia and hypotension are more commonly associated with rapid infusion of intravenous phenytoin. In our patient, the rate of intravenous phenytoin administration was <50 mg/min.Case Report: A 79-year-old woman presented to the emergency department with altered mental status for 2 h and focal seizure. After phenytoin was intravenously infused over 45 min, junctional rhythm, unresponsiveness, and hypotension developed. Atropine, dopamine, and transcutaneous pacing were initiated. After the intervention, a normal sinus rhythm with a normal heart rate was maintained. The patient was admitted to the neurological intensive care unit. Conclusion: Emergency physicians should monitor patients for possible arrhythmic effects of intravenous phenytoin therapy. In addition to geriatric patients and patients with a history of cardiac disease, there may be an increased risk of cardiotoxicity for phenytoin even at the recommended dose and infusion rate in patients with end-stage renal disease

Effects of perineural administration of phenytoin in combination with levobupivacaine in a rat sciatic nerve block

Peripheral nerve blocks are commonly preferred worldwide for the purposes of anesthesia application and postoperative analgesia. In this study, we investigated the effects of phenytoin which has a similar mechanism to local anesthetics in terms of the duration of analgesia and quality. The study was performed on 32 Sprague-Dawley male rats. Rats were randomly grouped into 4 groups. Group S: Sham group (n: 8); 0,2 ml saline perineural unilateral sciatic nerve. Group L: Perineural levobupivacaine (0,2 ml 0,5% levobupivacaine, n: 8); Group Ph: Perineural phenytoin (0,2 ml 62,5 mg / kg, n: 8); Group L + PH: Perineural phenytoin and levobupivacaine (0,2 ml 0,5% levobupivacaine + 62,5 mg / kg phenytoin, n: 8). Hot-plate and tail- flick tests were performed to measure acute thermal pain and histological changes were evaluated. The latency time at 30 minute in Group L+Ph were significantly increased when compared to the other groups during evaluation of the hot plate test. There was a significant difference in terms of latency time at 30 minute in Group L+Ph in the Tail Flick test and the latency time in Group L+Ph was longer when compared to the other groups (p

CEREBRAL VENOUS SINUS THROMBOSIS IN PATIENTS WITH METASTATIC TESTICULAR CANCER DURING CHEMOTHERAPY: REPORTS OF TWO CASES

Cerebral venous sinus thrombosis (CVT) is rare but sometimes develops in association with malignant neoplasm. We report two cases of CVT that occurred during cisplatin-based chemotherapy for testicular cancer. A 46-year-old man with stage IIA non-seminomatous germ cell tumour was treated with conventional doses of etoposide and cisplatin (EP). On day 11 of the third treatment course, he developed a systemic seizure. Brain computed tomography (CT) and magnetic resonance (MR) imaging could not detect the cause. Enhanced chest-pelvic CT revealed pelvic thrombosis. Administration of phenytoin for epilepsy of unknown cause and heparin for thrombosis was started. He had completed 4 courses of EP therapy without seizure recurrence. After re-evaluating the brain CT images retrospectively, we found high density of superior sagittal sinus (SSS) and strongly suspected CVT. Another patient was a 47-year-old man with stage IIIB seminomatous germ cell tumour treated with bleomycin, etoposide, and cisplatin (BEP) therapy. On day 11 of the second treatment course, he developed a systemic seizure. Brain CT revealed subarachnoid haemorrhage localised in the right parietal lobe. CT venography revealed a filling defect in the superior sagittal sinus (SSS). MR venography revealed a SSS stenosis. We diagnosed the cause of the seizure as CVT and started administration of anticoagulant therapy. After the thrombus had diminished, chemotherapy was restarted and another 2 courses of BEP therapy was completed.

DRESS Syndrome After Phenytoin Use: A Case Report

DRESS syndrome is alife threatening, rare hypersensitivity reaction to drugs with an acute onset that is characterized by fever, skin rash, visceral involvement, and hematological abnormalities. It is often seen after the use of aromatic anticonvulsants. In this article, a forty-four year old male patient with fever and skin rash after two weeks of phenytoin administration is discussed. He has been treated successfully with systemic corticosteroids and supportive therapy after the discontinuation of phenytoin therapy. In first step health-care, the primary physician should be able to administer his patients’ acute and chronic health problems concurrently. As in our case, a family physician should administer his patient well in the presence of fever with acute onset and he should question about the drugs used in the presence of accompanying skin rash.

Behavioral effects of antiepileptic drugs in rats: Are the effects on mood and behavior detectable in open-field test?

PurposeBehavioral side effects of antiepileptic drugs (AEDs) are common including both positive and negative effects on mood, anxiety, depression, and psychosis. We aimed to evaluate behavioral patterns in rats after administration of lamotrigine, levetiracetam, phenytoin, topiramate, carbamazepine, gabapentin, pregabalin, and zonisamide. MethodsThe open-field test was performed and locomotion, rearing, grooming, central latency and defecation were recorded over a 5min interval for each rat (8 rats in each group receiving AED and 16 controls). Kruskal-Wallis nonparametric test or ANOVA were used to assess differences among the groups. ResultsThe experimental groups did not differ in latency to enter the center compartment, neither in the decline of locomotor activity in the 1st and the 5th minute of the observation, nor in number of rears. Significant differences among groups were observed in the total number of lines crossed, grooming, as well in the number of fecal pellets. Locomotor activity was significantly increased in lamotrigine, if compared with gabapentin and pregabalin (ANOVA; p <0.05). Rats exposed to topiramate displayed a significantly increased number of grooming (when compared to pregabalin: p<0.01). Defecation (the number of fecal pellets) significantly increased in the gabapentin and carbamazepine group. ConclusionThere are significant differences between AEDs in terms of their behavioral profile. It is of great importance to evaluate these effects in clinical practice to bring more clear insight into these positive or negative side effects of AEDs.

Chronic administration of phenytoin and pleomorphic adenoma: A case report and review of literature

Adverse drug effects that are uncommon or appear only on chronic administration of a drug may not be detected in clinical trials. This explains the need of strict post-marketing vigilance on drug use. Phenytoin administration has been shown in the literature to be associated with development of neoplasia (benign/malignant). In our knowledge current work represents the first case of pleomorphic-adenoma of sub-mandibular salivary gland developed following chronic phenytoin use. A 40 year old male having a history of head trauma twenty years back, had been on tablet phenytoin 100 mg thrice daily since then. One year back he noticed a small swelling in left sub-mandibular region and gradually increasing in size. FNAC and CECT revealed the diagnosis of pleomorphic-adenoma of sub-mandibular salivary gland. Other causes were ruled out. Surgical excision was performed successfully and continuing follow-up with no recurrence at the end of 6 months. Histo-pathogical examination of the tissue did not show any malignant changes.

Effects of the Antiepileptic Drugs Phenytoin, Gabapentin, and Levetiracetam on Bone Strength, Bone Mass, and Bone Turnover in Rats.

Long-term treatment with antiepileptic drugs (AEDs) is accompanied by reduced bone mass that is associated with an increased risk of bone fractures. Although phenytoin has been reported to adversely influence bone metabolism, little is known pertaining to more recent AEDs. The aim of this study was to evaluate the effects of gabapentin or levetiracetam on bone strength, bone mass, and bone turnover in rats. Male Sprague-Dawley rats were orally administered phenytoin (20 mg/kg), gabapentin (30 or 150 mg/kg), or levetiracetam (50 or 200 mg/kg) daily for 12 weeks. Bone histomorphometric analysis of the tibia was performed and femoral bone strength was evaluated using a three-point bending method. Bone mineral density (BMD) of the femur and tibia was measured using quantitative computed tomography. Administration of phenytoin significantly decreased bone strength and BMD, which was associated with enhanced bone resorption. In contrast, treatment with gabapentin (150 mg/kg) significantly decreased bone volume and increased trabecular separation, as shown by bone histomorphometric analysis. Moreover, the bone formation parameters, osteoid volume and mineralizing surface, decreased after gabapentin treatment, whereas the bone resorption parameters, osteoclast surface and number, increased. Levetiracetam treatment did not affect bone strength, bone mass, and bone turnover. Our data suggested that gabapentin induced the rarefaction of cancellous bone, which was associated with decreased bone formation and enhanced bone resorption, and may affect bone strength and BMD after chronic exposure. To prevent the risk of bone fractures, patients prescribed a long-term administration of gabapentin should be regularly monitored for changes in bone mass.

Phenytoin Delayed Excretion because of Esomeprazole Co-administration

Background: Drug Interaction between Phenytoin and Esomeprazole is not commonly reported or widely recognized. A case of Phenytoin toxicity post prolonged administration of phenytoin and esomeprazole is reported. Case Summary: A 22 years old female diagnosed with MELAS (Mitochondrial myopathy, Encephalopathy, Lactic Acidosis, stroke like symptoms). She was maintained on Phenytoin 100 mg suspension via nasogastric tube every 8 hours as anticonvulsant for 3 years and esomeprazole 40 mg via nasogastric tube every 24 hours for hyperacidity. After 7 months from co-administration of phenytoin and esomeprazole the patient developed bradycardia, hypotension with nystagmus so upon checking the phenytoin trough serum level it was found to be 163 μmole/L, phenytoin was suspended and serum level monitored daily but it was found to be increasing to 167 μmole/L and the patient laboratory results showed leukopenia, thrombocytopenia and elevated liver enzymes, upon suspending Esomeprazole it was noticed that the Phenytoin serum level decreased dramatically by 10-20 μmole/L/day so the toxicity symptoms and abnormal laboratory results resolved upon normalization the Phenytoin serum level. Conclusion: Esomeprazole may competitively inhibit the CYP2C19 mediated Phenytoin metabolism which leads to prolonged exposure to high serum level and toxicities.

Clinical Profile and Changes of Serum Lipid Levels in Epileptic Patients after Cerebral Infarction

Antiepileptic drugs (AEDs) may increase development of dyslipidemia and cerebrovascular disease (CVD). We examined the clinical profile and changes of serum lipid levels after AED monotherapy in patients with poststroke epilepsy (PSE) after cerebral infarction (CI). Medical records were reviewed in consecutive 2144 CI patients. Monotherapy of valproate, carbamazepine (CBZ), phenytoin (PHT), zonisamide, levetiracetam, or lamotrigine was performed in PSE patients. Serum lipid levels were measured before and at 3 months after AED treatment. The prevalence of PSE was 7.0% in CI patients. The TOAST etiology disclosed large-artery atherosclerosis in 68 patients (45%), cardioembolism in 63 patients (42%), and undetermined cause in 19 patients (13%). CVD risk profile showed obesity of 18 patients (12%), current smoker of 30 patients (20%), hypertension of 75 patients (50%), diabetes mellitus of 32 patients (21%), dyslipidemia of 15 patients (10%), and atrial fibrillation of 63 patients (42%). CBZ or PHT administration increased serum total cholesterol (TC) and low-density lipoprotein-cholesterol (LDL-C) levels significantly compared to baseline and AED-untreated controls. Those levels were not increased significantly in other AED and control groups. Serum high-density lipoprotein-cholesterol and triglyceride levels did not differ statistically in all groups. The prevalence of post-CI epilepsy was 7.0%. The pathogenesis contributed to atherothrombosis and cardioembolism. CBZ or PHT administration increased serum TC and LDL-C significantly. Thus, we should pay more attention to serum lipid levels in patients receiving cytochrome P450 (CYP)-induced AEDs, and might considerer switching to non-CYP-induced AEDs in patients with unfavorable serum lipid changes.

Evaluation of Lymphocyte Transformation Test Results in Patients with Delayed Hypersensitivity Reactions following the Use of Anticonvulsant Drugs

Background/Aim: Administration of the anticonvulsant drugs phenobarbital, phenytoin, carbamazepine and lamotrigine can be associated with severe hypersensitivity reactions. The lymphocyte transformation test (LTT) is a method to determine which drug has caused the hypersensitivity reaction. This study was done to evaluate the results of LTT in patients with delayed hypersensitivity reactions following the administration of anticonvulsants. Methods: Twenty-four patients with hypersensitivity reactions, e.g. drug-induced hypersensitivity syndrome/drug rash and eosinophilia with systemic symptoms (DIHS/DRESS), Stevens-Johnson syndrome (SJS) and toxic epidermal necrosis (TEN), following the administration of anticonvulsant drugs, and 24 patients who had used anticonvulsant drugs but did not have hypersensitivity reactions (the control group) were included in this study. Peripheral blood mononuclear cells were isolated. The cells were stimulated with the drugs, phytohemagglutinin as a mitogen and Candida as an antigen (positive controls). Lymphocyte proliferation was measured using the BrdU proliferation assay kit (Roche, Germany). The stimulation index was calculated as the mean ratio of the OD of stimulated cells divided by the OD of unstimulated cells. The results in the case and control groups were compared. Results: Of 24 patients in the test group, 14 (58.3%) had positive LTT results and 10 (41.7%) had negative results. Among patients in the control group, 1 (4.2%) had a positive LTT result and 23 (95.8%) had negative results. Among the patients who had received carbamazepine and phenytoin, there was a significant difference between the results of LTT in the case and control groups (p = 0.002 and p = 0.028, respectively). Although patients receiving lamotrigine and phenobarbital had more positive LTT results in the case group than in the control group, these differences were not statistically significant. The sensitivity, specificity, positive predictive value and negative predictive value of LTT were 58.4, 95.8, 93.3 and 69.9%, respectively. Conclusions: Considering the significant difference in LTT results between the case and control groups in patients receiving carbamazepine and phenytoin, and not observing such a difference in patients receiving phenobarbital and lamotrigine, LTT results are more valuable for the diagnosis of hypersensitivity reactions following the administration of carbamazepine and phenytoin. The LTT has good specificity but low sensitivity for the diagnosis of drug hypersensitivity reactions.

Effects of duration of phenytoin administration on mRNA expression of cytochrome P450 and P-glycoprotein in the liver and small intestine of rats

Phenytoin (5,5-diphenylhydantoin; DPH) induces expression of cytochromes P450 (CYPs). Interactions between DPH and tacrolimus suggested that the persistence of CYP induction after discontinuation of DPH is dependent on the history of administration and dosing period of DPH. However, the relationship between the duration of DPH administration and expression of CYPs in the liver and small intestine of rats is not known. Alterations in levels of P-glycoprotein (P-gp; MDR1; ABCB1) as well as CYPs cause drug interactions in the small intestine. We examined the effects of the duration of DPH administration on expression of CYPs and P-gp in the liver and small intestine of rats. Rats were treated with DPH (100 mg/kg, peroral (p.o.) twice a day (b.d.)) for 2, 4, 8, and 16 d. mRNA levels of CYPs and P-gp were examined using the total RNA extracted from the liver and duodenum 2 h and 24 h after the final administration of DPH. CYP3A activities were determined using microsomes. DPH administration for 2 d and 4 d markedly increased mRNA levels of CYPs such as CYP3A1, CYP3A2, CYP2B1, and CYP2B2 in the liver. A relatively long duration of DPH administration (8 d and 16 d) resulted in abolition of the induction of hepatic CYP but increased CYP3A activities were maintained. These results suggest that the duration of DPH administration could be an important determinant of hepatic CYP induction.

An anaesthesiologist's encounter with purple glove syndrome.

Purple glove syndrome (PGS) is a devastating complication of intravenous (IV) phenytoin administration. Anaesthetic management during the amputation of the limb for such patients is very challenging due to limited clinical experience. A 65-year-old woman developed PGS of left upper extremity after IV administration of phenytoin following generalised tonic-clonic seizures. The condition progressed rapidly leading to gangrene of left hand extending to the mid arm. Amputation was carried out under general anaesthesia with a supraglottic airway device. We discuss the prevention and alternate managements in PGS, which is a rare clinical entity with limited data in the literature.

Phenytoin accelerates tendon healing in a rat model of Achilles tendon rupture.

Tendons are vulnerable to various types of acute or chronic injures. Different methods have been investigated to achieve better healing. Phenytoin is a drug which could stimulate fibroblasts to produce collagen. This experimental study was performed to assess the effect of phenytoin on tendon healing in a rat model of tendon rupture. Thirty healthy rats were divided into 3 groups, 1) Sham group; 2) Tendon rupture; 3) Tendon rupture+phenytoin (100 mg/kg intraperitoneally) for 21 days. On 21st day after tendon injury, the rats were anesthetized and tendon tissue was sampled for studying by light and electron microscopy. Qualitative and quantitative microscopic comparisons of the repair tissues of both groups were made on the 21st day. The results obtained from light and electron microscopy studies showed that tendon tissue healing was significantly better in phenytoin group compared to the control group (p < 0.05). Systemic administration of phenytoin may have a positive effect on tendon healing by increasing fibroblast quantity, fibrillar collagen synthesis, vascularity, and suppressing inflammation (Tab. 2, Ref. 25).

N-acetyltransferase 2 (NAT2) gene polymorphism as a predisposing factor for phenytoin intoxication in tuberculous meningitis or tuberculoma patients having seizures - A pilot study.

Background & objectives:Simultaneous administration of phenytoin and isoniazid (INH) in tuberculous meningitis (TBM) or tuberculoma patients with seizures results in higher plasma phenytoin level and thus phenytoin intoxication. N-acetyltransferase 2 (NAT2) enzyme catalyses two acetylation reactions in INH metabolism and NAT2 gene polymorphism leads to slow and rapid acetylators. The present study was aimed to evaluate the effect of allelic variants of N-acetyltransferase 2 (NAT2) gene as a predisposing factor for phenytoin toxicity in patients with TBM or tuberculoma having seizures, and taking INH and phenytoin simultaneously.Methods:Sixty patients with TBM or tuberculoma with seizures and taking INH and phenytoin simultaneously for a minimum period of seven days were included in study. Plasma phenytoin was measured by high performance liquid chromatography. NAT2 gene polymorphism was studied using restriction fragment length polymorphism and allele specific PCR.Results:The patients were grouped into those having phenytoin intoxication and those with normal phenytoin level, and also classified as rapid or slow acetylators by NAT2 genotyping. Genotypic analysis showed that of the seven SNPs (single nucleotide polymorphisms) of NAT2 gene studied, six mutations were found to be associated with phenytoin intoxication. For rs1041983 (C282T), rs1799929 (C481T), rs1799931 (G857A), rs1799930 (G590A), rs1208 (A803G) and rs1801280 (T341C) allelic variants, the proportion of homozygous mutant was higher in phenytoin intoxicated group than in phenytoin non-intoxicated group.Interpretation & conclusions:Homozygous mutant allele of NAT2 gene at 481site may act as a predisposing factor for phenytoin intoxication among TBM or tuberculoma patients having seizures.

難治てんかん患者を対象とした抗てんかん薬の薬物相互作用解析：

The purpose of this study was to evaluate interactions between antiepileptic drugs in patients with refractory epilepsy. Firstly, to compare the extent of enzyme induction among hepatic enzyme inducers (phenytoin (PHT), phenobarbital (PB), and carbamazepine (CBZ)), we analyzed the effects of these drugs on the pharmacokinetics of clobazam (CLB) and lamotrigine (LTG). Patients using PHT had significantly lower concentration /dose ratios of CLB and LTG than patients using PB or CBZ. However, an additive inducing effect was not observed when PHT was combined with CBZ and/or PB. Secondly, we retrospectively analyzed 2,724 adult patients and 1,826 pediatric patients treated with valproic acid (VPA) to evaluate whether drug interactions affected the incidence of hyperammonemia. We found that the plasma ammonia level increased markedly in a VPA dose-dependent manner. It was significantly elevated in patients who also used hepatic enzyme inducers, and concomitant administration of PHT was associated with the highest risk of hyperammonemia. Thus, PHT strongly induced CYPs and UGTs, and concomitant administration of PHT accelerated VPA metabolism, resulting in an increase of the ammonia level. These findings could be useful for predicting and minimizing drug interactions in patients receiving polypharmacy with antiepileptic drugs.

Amitriptyline and phenytoin prevents memory deficit in sciatic nerve ligation model of neuropathic pain.

Phenytoin and amitriptyline are often reported to attenuate pain in chronic conditions. Information on their ability to ameliorate cognitive impairment associated with neuropathic pain remains unclear due to mixed results from studies. This study investigated the effects of phenytoin and amitriptyline on memory deficit associated with neuropathic pain. Twenty-eight adult male Wistar rats were randomly divided into four groups: A, B, C, and D (n=7). Groups A, B, C, and D served as sham control, sciatic nerve ligated untreated, sciatic nerve ligated receiving amitriptyline (5 mg/kg), and sciatic nerve ligated receiving phenytoin (10 mg/kg) respectively. Treatments lasted for 14 days, after which both 'Y' maze and novel object recognition test (NOR) were performed. On the last day of treatment, the animals were anesthetized and their brain excised, and the prefrontal cortices and sciatic nerve were processed histologically using hematoxylin and eosin. There was memory impairment in the sciatic nerve ligated untreated group which was statistically significant (p<0.05) when compared to the phenytoin-treated, amitriptyline-treated, and sham control groups using the 'Y' maze and NOR tests. Histological quantification showed that the prefrontal cortices of the ligated animals showed increased neural population in comparison to normal control. These increases were significantly marked in the untreated ligated group. Sciatic nerve of untreated ligated group showed high demyelination and axonal degeneration which was ameliorated in the treated animals. The administration of amitriptyline and phenytoin can ameliorate neuronal injury, demyelination, and memory impairment associated with neuropathic pain in Wistar rats.