levetiracetam and Pain

Central post-stroke pain (CPSP) is a common condition. Several pharmacotherapies have been applied in practice. However, the comparative effectiveness among these pharmacotherapies is unknown.. The aim of this study is to study the comparative effectiveness among differential pharmacotherapies for CPSP through a network meta-analysis.. We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science from inception to 30 March 2022, without any language restriction. Two reviewers independently screened the retrieved articles, extracted data, and evaluated the risk of bias (RoB). The outcome of interest of the study was the change in the scores of pain intensity scales. We estimated standard mean differences (SMDs) between treatments and calculated corresponding 95% CIs.. Thirteen randomized controlled trials (529 participants) were included after a screen of 1774 articles. Compared with placebo, pamidronate (SMD -2.43, 95% CI -3.54 to -1.31;. Our study confirmed that pamidronate, prednisone, and guideline-recommended anticonvulsants were effective for reducing pain intensity for CPSP. Pamidronate and prednisone showed better effect than other pharmacotherapies, which warrants further investigation.

Topics: Anticonvulsants; Etanercept; Humans; Lamotrigine; Levetiracetam; Network Meta-Analysis; Pain; Pamidronate; Prednisone; Pregabalin

Oxcarbazepine, topiramate, zonisamide, and levetiracetam are the antiepileptic drugs (AEDs) most recently approved by the US Food and Drug Administration. Based on the experience with carbamazepine, gabapentin, and lamotrigine, these newer AEDs are being investigated for the management of neuropathic pain.. This article reviews preclinical and clinical data on the efficacy and tolerability of these 4 AEDs in the management of neuropathic pain, as well as the pharmacokinetics, drug-interaction potential, adverse effects, and dosing of these agents, with an emphasis on their use in older individuals.. Relevant studies were identified through a MEDLINE search of the Englidh-language literature published between 1986 and May 2003, a review of the reference lists of identified articles, and abstracts from the annual meetings of the American Academy of Neurology (1986-2002) and the 2003 Annual Meeting of the American Pain Society. Search terms were oxcarbazepine, topiramate, zonisamide, and levetiracetam.. Oxcarbazepine and topiramate have been effective in animal models of neuropathic pain. Thirty-four publications on the efficacy and tolerability of the 4 agents were identified (25 case reports/case series, 6 randomized parallel-group studies, and 3 randomized crossover studies). The 9 randomized studies were restricted to oxcarbazepine and topiramate, and 23 (68%) publications were available in abstract form only. These preliminary data suggest that the 4 newer AEDs may be useful in a wide variety of neuropathic pain syndromes; however, additional data, including full-length peer-reviewed reports, are necessary before their true analgesic potential in neuropathic pain can be determined. All 4 agents have pharmacodynamic interactions with other psychotherapeutic drugs, potentiating adverse central nervous system events such as sedation. With the exception of levetiracetam, these drugs also have pharmacokinetic interactions with other drugs, although to a somewhat lesser extent than carbamazepine. These agents have some unique adverse effects not frequently monitored by clinicians, such as hyponatremia, nephrolithiasis, acute myopia with secondary angle-closure glaucoma, and weight loss.. Based on preliminary data, oxcarbazepine, topiramate, zonisamide, and levetiracetam may be useful in the treatment of a wide variety of neuropathic pain syndromes, although full publication of the results of controlled trials is awaited. These agents are associated with specific adverse effects not commonly monitored by clinicians. Of the 4, levetiracetam appears to be easiest to use (ie, no need for dose adjustment in organ dysfunction, no need for laboratory monitoring) and best tolerated, and has not been associated with the unique toxicities seen with oxcarbazepine, topiramate, and zonisamide. The ultimate role of these agents in the therapeutic armamentarium against pain requires further research and experience. In the interim, these 4 agents should be used to treat neuropathic pain in the elderly only when carbamazepine, gabapentin, or lamotrigine cannot be used or when the response to the aforementioned agents is suboptimal.

Topics: Aged; Analgesics, Non-Narcotic; Animals; Carbamazepine; Clinical Trials as Topic; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Interactions; Fructose; Humans; Isoxazoles; Levetiracetam; Oxcarbazepine; Pain; Peripheral Nervous System Diseases; Piracetam; Topiramate; Zonisamide

The purpose of this open-label study was to assess the effectiveness and tolerability of levetiracetam (LEV) in the treatment of patients with lower lumbar radiculopathy diagnosed by clinical presentation, physical examination, and electrodiagnostics.. Open-label, forced titration, prospective cohort intent-to-treat analysis.. Major teaching hospital.. Participants were recruited from the university pain clinic and through referrals from the community. Subjects were eligible to participate if they (1) were older than 18 years, (2) had leg pain greater than back pain, (3) had been symptomatic for 6 months and <5 years, (3) had a baseline visual analog scale of at least 6 on the 0-10 scale, (4) had undergone lumbar spine magnetic resonance imaging within the last 12 months that showed no surgically correctable etiology for their radicular symptoms, and (5) had undergone electrodiagnostics that was positive for lumbar radiculopathy (L4, L5, or S1 nerve roots). Twenty-six patients were enrolled, and 24 (92.3%) completed the study.. Patients initially received LEV 500 mg twice a day for 2 weeks. Dosages were then increased to 750 mg twice day for 2 weeks, and then to 1500 mg twice a day for the remainder of the study. Patients were observed for 8 weeks after reaching the maximum dose.. Treatment effectiveness was assessed with the use of biweekly brief pain inventory and patient global assessment scales. Frequency and severity of adverse events were recorded.. The mean biweekly worst and average pain scores decreased from 7.17 and 6.27 at baseline to 4.2 and 3.9, respectively, at week 12 (P < or = .001). Improvements were reported in general activity, ability to walk, mood, and relationship with people. Side effects consisted of sedation/drowsiness (46%), gastrointestinal upset (23%), headache (19%), blurred vision (15%), weakness/fatigue (11%), and dyscoordination (11%).. This study showed that LEV might be a well-tolerated and effective treatment for lumbar radiculopathy. A large randomized placebo-controlled trial is recommended and comparative studies with alternative agents should be sought.

Topics: Adult; Aged; Analgesics; Female; Humans; Levetiracetam; Lumbar Vertebrae; Male; Middle Aged; Pain; Pain Measurement; Piracetam; Radiculopathy

Antiseizure medications (ASMs) are frequently used for other indications, such as migraine, pain syndromes, and psychiatric disorders. Possible teratogenic effects are therefore of wide concern and the risks imposed by the medications must be weighed against the risk with the disorder treated. It is our objective to update family practitioners on the implications of starting ASM for women with epilepsy during childbearing age. We hypothesized that clinicians would prescribe ASM based on avoiding teratogenesis and treating associated comorbidities simultaneously.. The study cohort was derived from women veterans with epilepsy (WVWE) prescribed ASM who received Veterans Health Administration care for at least 3 years in Veterans Health Administration between fiscal years (FY)01 and FY19. Regimens were classified as monotherapy or polytherapy. Multivariant logistic regression examined the association between demographics, military characteristics, physical/psychiatric comorbidities, neurological care, and use of each ASM.. Among 2,283 WVWE, in ages between 17 and 45, the majority (61%) received monotherapy in FY19. Commonly prescribed ASM included 29% gabapentin, 27% topiramate, 20% lamotrigine, 16% levetiracetam, and 8% valproate (VPA). Comorbid diagnosis of headache predicted use of topiramate and VPA, bipolar disease predicted use of LMT and VPA, pain predicted gabapentin, and schizophrenia was associated with VPAs use. Women receiving levetiracetam and lamotrigine were significantly more likely to receive neurology care previously.. The presence of medical comorbidities influences the selection of ASM. VPAs use in WVWE during childbearing age continues, despite the high teratogenic risk, especially in women with bipolar disorder and headaches. Multidisciplinary care integrating family practice doctors, mental health, and neurology can prevent the enduring problem of teratogenesis in women taking ASM.

Topics: Adolescent; Adult; Anticonvulsants; Epilepsy; Female; Gabapentin; Humans; Lamotrigine; Levetiracetam; Middle Aged; Pain; Pharmaceutical Preparations; Teratogenesis; Topiramate; Valproic Acid; Veterans; Young Adult

Traditional and novel analgesic modalities have been extensively tested for post-craniotomy pain management, yet the role of newer antiepileptic drugs in this area remains obscure. This study investigates the impact of levetiracetam (LEV) on pain modulation and neurobehavioral performance in a craniotomy model. Fifty-six Wistar rats were randomly assigned into seven groups: no intervention (CTRL), administration of placebo or LEV with no further intervention (PBO and LEV, respectively), and sham-operation or craniotomy in placebo (PBO-SHAM and PBO-CR, respectively) or LEV-treated rats (LEV-SHAM and LEV-CR, respectively). Pain was assessed by the rat grimace scale before, and at 8 and 24 h after craniotomy, following intraperitoneal injections of LEV (100 mg/kg twice daily) or normal saline two consecutive days before and on the craniotomy day. Elevated plus-maze and olfactory social memory tests were performed at 24- and 48 h post-craniotomy, respectively. Upon testing conclusion blood samples were collected for cytokines estimation. Levetiracetam administration enhanced antinociception in sham and craniotomy groups. In the elevated plus-maze test, LEV-CR rats spent more time in investigating open arms and performed more open arm entries than PBO-SHAM and PBO-CR animals. The olfactory test revealed no between-groups difference in acquisition time during first contact with a juvenile rat, while LEV-CR rats spent less time to recognize the same juvenile rat compared to PBO-SHAM and PBO-CR groups. Furthermore, LEV-treatment attenuated cortisol, interleukin-6 and TNF-a release, in sham and craniotomy animals. In conclusion, preemptive use of LEV decreases nociception, improves pain-evoked behavior and attenuates stress response in rats subjected to craniotomy.

Topics: Animals; Anticonvulsants; Craniotomy; Levetiracetam; Male; Nociception; Pain; Rats; Rats, Wistar

Levetiracetam (LEV) is a novel anticonvulsant with proven antinociceptive properties. However, the antinociceptive and pronociceptive effect of this drug has not yet been fully elucidated in a tonic pain model.. Thirty-six male rats (Wistar) were randomized into six groups and underwent the formalin test as follows: rats in the control group were administered 50μL of 1% formalin in the paw; sham-group rats were administered 50μL of saline in the paw to mimick the application of formalin; the four experimental groups were administered LEV intragastrically (ig) (50, 100, 200 and 300mg/kg), and 40min later 50μL of 1% formalin was injected in the paw.. LEV exhibited antinociceptive effect in the 300mg/kg LEV group (p<0.05) and a pronociceptive effect in the 100mg/kg LEV group (p<0.05) and in the 50mg/kg LEV group (p<0.001).. The antinociceptive and pronociceptive effect of LEV in a tonic pain model is dose-dependent.

Topics: Analgesics; Animals; Anticonvulsants; Disease Models, Animal; Dose-Response Relationship, Drug; Levetiracetam; Male; Nociception; Pain; Pain Measurement; Piracetam; Rats; Rats, Wistar

The purpose of this study was to synthetize the focused library of 34 new piperazinamides of 3-methyl- and 3,3-dimethyl-(2,5-dioxopyrrolidin-1-yl)propanoic or butanoic acids as potential new hybrid anticonvulsants. These hybrid molecules join the chemical fragments of well-known antiepileptic drugs (AEDs) such as ethosuximide, levetiracetam, and lacosamide. Compounds 5-38 were prepared in a coupling reaction of the 3-methyl- or 3,3-dimethyl-2-(2,5-dioxopyrrolidin-1-yl)propanoic (1, 2) or butanoic acids (3, 4) with the appropriately substituted secondary amines in the presence of the N,N-carbonyldiimidazole reagent. The initial anticonvulsant screening was performed in mice (ip) using the 'classical' maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) tests as well as in the six-Hertz (6Hz) model of pharmacoresistant limbic seizures. The acute neurological toxicity was determined applying the chimney test. The broad spectra of activity across the preclinical seizure models in mice ip displayed compounds 7, 15, and 36. The most favorable anticonvulsant properties demonstrated 15 (ED50 MES=74.8mg/kg, ED50scPTZ=51.6mg/kg, ED50 6Hz=16.8mg/kg) which showed TD50=213.3mg/kg in the chimney test that yielded satisfying protective indexes (PI MES=2.85, PI scPTZ=4.13, PI 6Hz=12.70) at time point of 0.5h. As a result, compound 15 displayed comparable or better safety profile than clinically relevant AEDs: ethosuximide, lacosamide or valproic acid. In the in vitro assays compound 15 was observed as relatively effective binder to the neuronal voltage-sensitive sodium and L-type calcium channels. Beyond the anticonvulsant properties, 6 compounds diminished the pain responses in the formalin model of tonic pain in mice.

Topics: Analgesics; Animals; Anticonvulsants; Disease Models, Animal; Dose-Response Relationship, Drug; Electroshock; Injections, Intraperitoneal; Mice; Molecular Structure; Pain; Pain Measurement; Pentylenetetrazole; Piperazines; Pyrrolidinones; Seizures

Painful diabetic neuropathy is difficult to treat. Single analgesics often have insufficient efficacy and poor tolerability. Combination therapy may therefore be of particular benefit, because it might provide optimal analgesia with fewer adverse effects. This study aimed to examine the type of interaction between levetiracetam, a novel anticonvulsant with analgesic properties, and commonly used analgesics (ibuprofen, aspirin and paracetamol) in a mouse model of painful diabetic neuropathy. Diabetes was induced in C57BL/6 mice with a single high dose of streptozotocin, applied intraperitoneally (150 mg/kg). Thermal (tail-flick test) and mechanical (electronic von Frey test) nociceptive thresholds were measured before and three weeks after diabetes induction. The antinociceptive effects of orally administered levetiracetam, analgesics, and their combinations were examined in diabetic mice that developed thermal/mechanical hypersensitivity. In combination experiments, the drugs were co-administered in fixed-dose fractions of single drug ED50 and the type of interaction was determined by isobolographic analysis. Levetiracetam (10-100 mg/kg), ibuprofen (2-50 mg/kg), aspirin (5-75 mg/kg), paracetamol (5-100 mg/kg), and levetiracetam-analgesic combinations produced significant, dose-dependent antinociceptive effects in diabetic mice in both tests. In the tail-flick test, isobolographic analysis revealed 15-, and 19-fold reduction of doses of both drugs in the combination of levetiracetam with aspirin/ibuprofen, and paracetamol, respectively. In the von Frey test, approximately 7- and 9-fold reduction of doses of both drugs was detected in levetiracetam-ibuprofen and levetiracetam-aspirin/levetiracetam-paracetamol combinations, respectively. These results show synergism between levetiracetam and ibuprofen/aspirin/paracetamol in a model of painful diabetic neuropathy and might provide a useful approach to the treatment of patients suffering from painful diabetic neuropathy.

Topics: Acetaminophen; Analgesics; Animals; Aspirin; Diabetic Neuropathies; Dose-Response Relationship, Drug; Drug Synergism; Hot Temperature; Ibuprofen; Levetiracetam; Male; Mice; Mice, Inbred C57BL; Pain; Pain Measurement; Pain Threshold; Physical Stimulation; Piracetam; Postural Balance

The β-lactam antibiotic ceftriaxone stimulates glutamate transporter GLT-1 expression and is effective in neuropathic and visceral pain models. This study examined the effects of ceftriaxone and its interactions with different analgesics (ibuprofen, celecoxib, paracetamol, and levetiracetam) in somatic and visceral pain models in rodents.. The effects of ceftriaxone (intraperitoneally/intraplantarly), analgesics (orally), and their combinations were examined in the carrageenan-induced paw inflammatory hyperalgesia model in rats (n = 6-12) and in the acetic acid-induced writhing test in mice (n = 6-10). The type of interaction between ceftriaxone and analgesics was determined by isobolographic analysis.. Pretreatment with intraperitoneally administered ceftriaxone (10-200 mg/kg per day) for 7 days produced a significant dose-dependent antihyperalgesia in the somatic inflammatory model. Acute administration of ceftriaxone, via either intraperitoneal (10-200 mg/kg) or intraplantar (0.05-0.2 mg per paw) routes, produced a significant and dose-dependent but less efficacious antihyperalgesia. In the visceral pain model, significant dose-dependent antinociception of ceftriaxone (25-200 mg/kg per day) was observed only after the 7-day pretreatment. Isobolographic analysis in the inflammatory hyperalgesia model revealed approximately 10-fold reduction of doses of both drugs in all examined combinations. In the visceral nociception model, more than 7- and 17-fold reduction of doses of both drugs was observed in combinations of ceftriaxone with ibuprofen/paracetamol and celecoxib/levetiracetam, respectively.. Ceftriaxone exerts antihyperalgesia/antinociception in both somatic and visceral inflammatory pain. Its efficacy is higher after a 7-day pretreatment than after acute administration. The two-drug combinations of ceftriaxone and the nonsteroidal analgesics/levetiracetam have synergistic interactions in both pain models. These results suggest that ceftriaxone, particularly in combinations with ibuprofen, celecoxib, paracetamol, or levetiracetam, may provide useful approach to the clinical treatment of inflammation-related pain.

Topics: Acetaminophen; Analgesics; Analgesics, Non-Narcotic; Animals; Anti-Bacterial Agents; Ceftriaxone; Celecoxib; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Synergism; Drug Therapy, Combination; Hyperalgesia; Ibuprofen; Inflammation; Levetiracetam; Male; Pain; Piracetam; Pyrazoles; Rats; Rats, Wistar; Sulfonamides

To evaluate the tolerability and clinical effects of subcutaneous (SC) levetiracetam for the treatment of epileptic seizures in a palliative care setting, we conducted a retrospective chart review of patients treated with subcutaneous levetiracetam in the Department of Palliative Medicine at the University Munich, between September 2006 and March 2013. The following parameters were extracted from the charts: reason for antiepileptic drug treatment, daily dose, concentration, infusion rate, co-administration of other drugs, and clinical effects. Furthermore, the charts were screened for signs of adverse drug reactions, e.g., irritation or pain at the infusion site. We identified 20 patients that were treated with levetiracetam SC in the inpatient (n = 7) and outpatient (n = 13) settings. Most patients (n = 17) tolerated the subcutaneous infusion well. Nineteen patients (95%) received levetiracetam in combination with other drugs. These were mainly metamizol (80%), midazolam (75%), and morphine (45%). The median dose of levetiracetam was 95.8 mg/h (SD 37 mg/h), median osmolarity of the infusion solution 2203 mOsmol/L (SD 717 mOsmol/L), and infusion rate 2 mL/h (SD 2.4 ml/h). In 16 patients (80%), seizures were controlled and status epilepticus were interrupted, respectively. We conclude that SC levetiracetam is an effective treatment and well tolerated in the palliative care setting.

Topics: Adult; Aged; Aged, 80 and over; Anticonvulsants; Drug Therapy, Combination; Epilepsy; Female; Humans; Infusions, Subcutaneous; Levetiracetam; Male; Middle Aged; Pain; Piracetam; Retrospective Studies; Treatment Outcome

Levetiracetam (LEV), a new anticonvulsant agent primarily used to treat epilepsy, has been used in pain treatment but the cellular mechanism of this action remains unclear. This study aimed to investigate effects of LEV on the excitability and membrane depolarization-induced calcium signaling in isolated rat sensory neurons using the whole-cell patch clamp and fura 2-based ratiometric Ca(2+)-imaging techniques. Dorsal root ganglia (DRG) were excised from neonatal rats, and cultured following enzymatic and mechanical dissociation. Under current clamp conditions, acute application of LEV (30 µM, 100 µM and 300 µM) significantly increased input resistance and caused the membrane to hyperpolarize from resting membrane potential in a dose-dependent manner. Reversal potentials of action potential (AP) after hyperpolarising amplitudes were shifted to more negative, toward to potassium equilibrium potentials, after application of LEV. It also caused a decrease in number of APs in neurons fired multiple APs in response to prolonged depolarization. Fura-2 fluorescence Ca(2+) imaging protocols revealed that HiK(+) (30 mM)-induced intracellular free Ca(2+) ([Ca(2+)](i)) was inhibited to 97.8 ± 4.6% (n = 17), 92.6 ± 4.8% (n = 17, p < 0.01) and 89.1 ± 5.1% (n = 18, p < 0.01) after application of 30 µM, 100 µM and 300 µM LEV (respectively), without any significant effect on basal levels of [Ca(2+)](i). This is the first evidence for the effect of LEV on the excitability of rat sensory neurons through an effect which might involve activation of potassium channels and inhibition of entry of Ca(2+), providing new insights for cellular mechanism(s) of LEV in pain treatment modalities.

Topics: Action Potentials; Analgesics; Animals; Anticonvulsants; Calcium; Dose-Response Relationship, Drug; Electrophysiology; Epilepsy; Fluorescent Dyes; Fura-2; Ganglia, Spinal; Levetiracetam; Neurons; Pain; Patch-Clamp Techniques; Piracetam; Rats; Sensory Receptor Cells

We have recently shown that levetiracetam, administered systemically, exerts an antihyperalgesic effect in a rat inflammatory pain model. In this study, we examined whether levetiracetam has local peripheral antihyperalgesic/anti-edematous effects in the same model of localized inflammation and whether opioidergic, adrenergic, purinergic, 5-HTergic, and GABAergic receptors are involved in its antihyperalgesic action.. Rats were intraplantarly (IPL) injected with carrageenan. A paw pressure test was used to determine the effect/s of (a) levetiracetam when applied IPL, on carrageenan-induced hyperalgesia, and (b) naloxone (a nonselective opioid receptor antagonist), CTAP (a selective μ-opioid receptor antagonist); yohimbine (a selective α(2)-adrenoceptor antagonist), BRL 44408 (a selective α(2A)-adrenoceptor antagonist), MK-912 (a selective α(2C)-adrenoceptor antagonist); caffeine (a nonselective adenosine receptor antagonist), DPCPX (a selective adenosine A(1) receptor antagonist); methysergide (a nonselective 5-HT receptor antagonist), GR 127935 (a selective 5-HT(1B/1D) receptor antagonist); and bicuculline (a selective GABA(A) receptor antagonist), all applied IPL, on the levetiracetam-induced antihyperalgesia. Moreover, levetiracetam's influence on paw inflammatory edema was measured by plethysmometry.. Levetiracetam (200-1000 nmol/paw) produced a significant dose-dependent reduction of the paw inflammatory hyperalgesia and edema induced by carrageenan. Naloxone (75-300 nmol/paw), CTAP (1-5 nmol/paw); yohimbine (130-520 nmol/paw), BRL 44408 (50-200 nmol/paw), MK-912 (5-20 nmol/paw); caffeine (500-1500 nmol/paw), DPCPX (3-30 nmol/paw); methysergide (10-100 nmol/paw) and GR 127935 (50-200 nmol/paw); but not bicuculline (400 nmol/paw), significantly depressed the antihyperalgesic effects of levetiracetam (1000 nmol/paw). The effects of levetiracetam and antagonists were attributed to local peripheral effects because they were not observed after administration into the contralateral hind-paw.. Our results show that levetiracetam produces local peripheral antihyperalgesic and anti-edematous effects in a rat model of localized inflammation. Antihyperalgesia is at least in part mediated by peripheral μ-opioid, α2A,C-adrenergic, A1 adenosine, and 5-HT1B/1D receptors, but not by GABAA receptors. These findings could contribute toward a better understanding of the analgesic effects of levetiracetam, and improved treatments of inflammatory pain with a lower incidence of systemic side effects and drug interactions of levetiracetam.

Topics: Adenosine A1 Receptor Antagonists; Adrenergic alpha-Antagonists; Anesthetics, Local; Animals; Carrageenan; Drug Interactions; Edema; Foot; GABA Antagonists; Hindlimb; Hyperalgesia; Inflammation; Levetiracetam; Male; Pain; Peripheral Nerves; Piracetam; Plethysmography; Rats; Rats, Wistar; Receptors, Opioid; Serotonin Antagonists

Levetiracetam, a novel antiepileptic drug, has recently been shown to have antinociceptive effects in various animal models of pain. The purpose of this study was to investigate the antihyperalgesic effect of levetiracetam and its mechanism of action, by examining the involvement of GABAergic, opioidergic, 5-hydroxytryptaminergic (5-HTergic) and adrenergic systems in its effect, in a rat model of inflammatory pain.. Rats were intraplantarly injected with the pro-inflammatory compound carrageenan. A paw pressure test was used to determine: (i) the effect of levetiracetam on carrageenan-induced hyperalgesia; and (ii) the effects of bicuculline (selective GABA(A) receptor antagonist), naloxone (non-selective opioid receptor antagonist), methysergide (non-selective 5-HT receptor antagonist) and yohimbine (selective alpha(2)-adrenoceptor antagonist) on the antihyperalgesic action of levetiracetam.. Levetiracetam (10-200 mg.kg(-1); p.o.) significantly reduced, in a dose-dependent manner, the inflammatory hyperalgesia induced by carrageenan. The antihyperalgesic effect of levetiracetam was significantly decreased after administration of bicuculline (0.5-2 mg.kg(-1); i.p.), naloxone (1-3 mg.kg(-1); i.p.), methysergide (0.25-1 mg.kg(-1); i.p.) and yohimbine (1-3 mg.kg(-1); i.p.).. These results show that levetiracetam produced antihyperalgesia which is at least in part mediated by GABA(A), opioid, 5-HT and alpha(2)-adrenergic receptors, in an inflammatory model of pain. The efficacy of levetiracetam in this animal model of inflammatory pain suggests that it could be a potentially important agent for treating inflammatory pain conditions in humans.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Carrageenan; Disease Models, Animal; Hyperalgesia; Levetiracetam; Male; Narcotic Antagonists; Pain; Piracetam; Rats; Rats, Wistar; Receptors, Adrenergic, alpha-2; Receptors, GABA-A; Receptors, Opioid; Receptors, Serotonin

Despite important advances in available knowledge, management of neuropathic pain remains incomplete, and results from experimental and clinical studies indicate that some anticonvulsants show promise for treating neuropathic pain. The aim of this study was to assess the antinociceptive efficacy of levetiracetam (LEV, ucb L059) in a mice model for painful diabetic neuropathy using the in vivo nociceptive behavioral 'hot-plate test.'. The hot-plate test consisted of placing individual mice (adult male Balb/C) on the hot plate at 50+/-0.1 degrees C and timing the delay for the first hind paw lift (nociceptive threshold). After obtaining control values, diabetes was induced by injection of streptozotocin [200 mg/kg intraperitoneally (i.p.)] and 2 weeks after induction of diabetes (serum glucose > or =400 mg/dL) LEV was administered i.p. and hot-plate tests were repeated. Pain threshold values were determined and analyzed by Kruskal-Wallis one-way analysis of variance (ANOVA) followed by a pairwise comparison using a Dunnett's t-test on the ranked data.. LEV (60, 300 and 900 mg/kg) had no significant effect on the nociceptive threshold in normal mice (n=8 for each dose, P>0.05). There were significant decreases in pain threshold latency in diabetic mice compared with the normal healthy group and these were significantly and dose-dependently restored by much lower doses of LEV (20, 100 and 200 mg/kg) in a reversible manner.. Results obtained from the in vivo behavioral test lend support to the validation of the promising therapeutic potential of the novel antiepileptic agent LEV in the treatment of neuropathic pain.

Topics: Analgesics; Animals; Anticonvulsants; Behavior, Animal; Diabetic Neuropathies; Disease Models, Animal; Dose-Response Relationship, Drug; Hot Temperature; Levetiracetam; Male; Mice; Mice, Inbred BALB C; Pain; Pain Measurement; Piracetam; Time Factors; Treatment Outcome

Certain types of pain associated with cancer may be difficult to treat with standard therapies, often resulting in intractable pain and suffering for the patient. The use of an opioid as analgesic monotherapy can lead to poorly controlled pain as well as multiple side effects. Non-opioid adjunctive analgesics, such as antidepressants and antiepileptic drugs (AEDs) often improve both pain control, and side effect prevalence. Levetiracetam is an AED with unique mechanisms of action that may have analgesic properties in various pain syndromes. Seven patients with neoplasms involving neural structures (four invading the brachial plexus, and three the lumbosacral plexus) had severe pain of 8 to 9 out of 10 on a visual analog scale (VAS), despite the use of parenteral opioids and various adjunctive therapies. These patients were treated with oral levetiracetam titrated over days to two weeks, depending on the location of pain, drug response, and tolerance to tapering of opioid analgesics. Opioid and adjunctive analgesic use and VAS scores were recorded periodically. The maximum levetiracetam dose ranged from 500 mg to 1500 mg BID. All patients experienced pain control improvement after the addition of levetiracetam, with VAS scores decreasing from 8-9 out of 10 to 0-3 out of 10 within two to 14 days of therapy initiation. Overall opioid use decreased by at least an estimated 70%, without drug related adverse events. In this small series of patients, levetiracetam effectively and safely improved pain relief in patients with neoplastic plexopathies previously resistant to standard analgesic approaches.

Topics: Adult; Aged; Analgesics, Opioid; Anticonvulsants; Brachial Plexus Neuropathies; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Humans; Levetiracetam; Lumbosacral Plexus; Male; Middle Aged; Neoplasms; Pain; Peripheral Nervous System Diseases; Piracetam

The purpose of this study was to assess, in rats, the antinociceptive effects of levetiracetam (i.p.), a novel antiepileptic drug, in acute pain tests and in two models of human neuropathic pain. Levetiracetam and carbamazepine contrasted morphine by an absence of effect in the tail flick and hot plate tests. In normal rats, carbamazepine failed to modify the vocalisation thresholds to paw pressure whereas levetiracetam slightly increased this threshold only at the highest dose (540 mg/kg) for 30 min. In the sciatic nerve with chronic constriction injury model, the highest dose of levetiracetam (540 mg/kg) and carbamazepine (30 mg/kg) reversed the hyperalgesia. In streptozocin-induced diabetic rats, levetiracetam dose-dependently increased the vocalization threshold from 17 to 120 mg/kg reaching a similar effect as 10 mg/kg of carbamazepine. These results indicate that levetiracetam induces an antihyperalgesic effect in two models of human neuropathic pain, suggesting a therapeutic potential in neuropathic pain patients.

Topics: Acute Disease; Analgesics; Animals; Carbamazepine; Chronic Disease; Constriction, Pathologic; Diabetes Mellitus, Experimental; Disease Models, Animal; Dose-Response Relationship, Drug; Humans; Hyperalgesia; Injections, Intraperitoneal; Levetiracetam; Male; Morphine; Pain; Pain Measurement; Peripheral Nervous System Diseases; Piracetam; Rats; Rats, Sprague-Dawley; Sciatic Nerve; Vocalization, Animal

Topics: Acetaminophen; Acetates; Amines; Analgesics; Animals; Cyclohexanecarboxylic Acids; Disease Models, Animal; Drug Delivery Systems; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Levetiracetam; Nitrates; Pain; Peripheral Nervous System Diseases; Piracetam; Pregabalin; Topiramate