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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pregabalin is an anticonvulsant drug that is under review for use in Canada. It was recently approved in the US and Europe for the treatment of adults with peripheral neuropathic pain (NeP). In most short-term randomized controlled trials (RCTs) of pregabalin in patients with diabetic peripheral neuropathy (DPN) and or post-herpetic neuralgia (PHN), there were early and significant decreases in mean pain scores. The number of subjects with > 50% reduction in pain score was increased when pregabalin was compared to placebo. The most common adverse effects were dizziness and sleepiness. Withdrawal due to adverse events was also more frequent with pregabalin than with placebo. While pregabalin appears to be an effective treatment for NeP, there is no evidence that it offers advantages over treatments being used in Canada.
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PMID:Pregabalin for peripheral neuropathic pain. 1580 48

Pregabalin binds with high affinity to the alpha2-delta subunit protein of voltage-gated calcium channels and, thereby, reduces release of excitatory neurotransmitters. This 12-week randomised, double-blind, multicentre, placebo-controlled, parallel-group study evaluated the efficacy and safety of pregabalin in patients with chronic postherpetic neuralgia (PHN) or painful diabetic peripheral neuropathy (DPN). Patients were randomised to placebo (n=65) or to one of two pregabalin regimens: a flexible schedule of 150, 300, 450, and 600 mg/day with weekly dose escalation based on patients' individual responses and tolerability (n=141) or a fixed schedule of 300 mg/day for 1 week followed by 600 mg/day for 11 weeks (n=132). Both flexible- and fixed-dose pregabalin significantly reduced endpoint mean pain score (primary outcome) versus placebo (P=0.002, P<0.001) and were significantly superior to placebo in improving pain-related sleep interference (P<0.001). The most common adverse events (AEs) for pregabalin-treated patients were dizziness, peripheral oedema, weight gain (not affecting diabetes control), and somnolence. These results are consistent with previous studies' demonstrating pregabalin's efficacy, tolerability, and safety for treatment of chronic neuropathic pain associated with DPN or PHN. Pregabalin dosing aimed at optimal balance of efficacy and tolerability provides significant pain relief and may reduce risks for AEs and therapy discontinuation.
Pain 2005 Jun
PMID:Efficacy of pregabalin in neuropathic pain evaluated in a 12-week, randomised, double-blind, multicentre, placebo-controlled trial of flexible- and fixed-dose regimens. 1591 Nov 52

Pregabalin (Lyrica, Pfizer) is a GABA analog with similar structure and actions to gabapentin. It has antiepileptic, analgesic and anxiolytic activity. Pregabalin is indicated for the management of neuropathic pain associated with diabetic neuropathy and post-herpetic neuralgia. Peak plasma levels occur approximately 1 hour after oral doses and oral bioavailability is about 90%. Based on AUC data, food does not significantly affect the extent of absorption. Pregabalin is not protein-bound and exhibits a plasma half-life of about 6 hours, which is not dose-dependent. Hepatic metabolism is negligible, and most of the oral dose (95%) appears unchanged in the urine. Pregabalin is a safe and well-tolerated new treatment for neuropathic pain. Furthermore, pregabalin has proven efficacy in adjunctive therapy of refractory partial seizures and in the treatment of acute pain, generalized anxiety disorder and social phobia.
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PMID:Pregabalin: a new agent for the treatment of neuropathic pain. 1623 74

Pregabalin (Lyrica) is a novel amino acid compound that binds with high affinity to the alpha2-delta (alpha2-delta) auxiliary protein of voltage-gated calcium channels. In vivo, it potently prevents seizures, pain-related behaviors and has anxiolytic-like activity in rodent models. The present studies were performed to determine the profile of pregabalin anticonvulsant activity in a variety of mouse and rat models. In the high-intensity electroshock test, pregabalin potently inhibited tonic extensor seizures in rats (ED50 = 1.8 mg/kg, PO), and low-intensity electroshock seizures in mice. It prevented tonic extensor seizures in the DBA/2 audiogenic mouse model (ED50 = 2.7 mg/kg, PO). Its time course of action against electroshock induced seizures in rats roughly followed the pharmacokinetics of radiolabeled drug in the brain compartment. At higher dosages (ED50 1= 31 mg/kg, PO), pregabalin prevented clonic seizures from pentylenetetrazole in mice. In a kindled rat model of partial seizures, pregabalin prevented stages 4-5 behavioral seizures (lowest effective dose = 10 mg/kg, IP), and also reduced the duration of electrographic seizures. Pregabalin was not active to prevent spontaneous absence-like seizures in the Genetic Absence Epilepsy in Rats from Strasbourg (GAERS) inbred Wistar rat strain. Pregabalin caused ataxia and decreased spontaneous locomotor activity at dosages 10-30-fold higher than those active to prevent seizures. These findings suggest that pregabalin has an anticonvulsant mechanism different from the prototype antiepileptic drugs and similar to that of gabapentin except with increased potency and bioavailability. In summary, our results show that pregabalin has several properties that favor treatment of partial seizures in humans.
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PMID:Activity profile of pregabalin in rodent models of epilepsy and ataxia. 1633 9

(1) The first-line treatment for partial epilepsy is carbamazepine monotherapy; gabapentin monotherapy is an alternative, given its lower risk of drug-drug interactions. (2) The standard treatment for neuropathic pain associated with diabetes or post-herpetic neuralgia is a tricyclic antidepressant, with gabapentin as an alternative. Few drugs are available in this setting, and their efficacy is often modest. (3) Pregabalin is a GABA analogue closely related to gabapentin. Both drugs are marketed by Pfizer. Pregabalin has been approved for use in two indications: refractory partial epilepsy and neuropathic pain. (4) In patients with partial epilepsy inadequately controlled by a combination of two or possibly three antiepileptics, three placebo-controlled double-blind trials lasting 12 weeks suggest that adjunctive pregabalin treatment, at a dose of 600 mg/day divided in two or three doses, at least halves the frequency of seizures in 50% of patients. Pregabalin has not been compared with other second-line antiepileptics. (5) In neuropathic pain, there are 12 double-blind placebo-controlled trials involving patients with diabetes or post-herpetic neuralgia. Depending on the trial, between one-third and one-half of patients treated with pregabalin at a dose of 600 mg/day given in two or three doses had at least a 50% reduction in their pain score. In the only trial that included a group treated with amitriptyline (75 mg/day), the latter was significantly more effective than placebo, while pregabalin was not. (6) There are no comparative trials of pregabalin after amitriptyline and gabapentin failure. (7) The adverse effects profile of pregabalin is similar to that of gabapentin, and includes mainly neuropsychological reactions (dizziness and drowsiness). (8) Pregabalin, like gabapentin, can lead to weight gain and peripheral oedema especially in elderly patients. (9) Cases of visual field restriction have been reported with pregabalin in clinical trials. Animal studies suggest a possible risk of haemangiosarcoma, although no human cases have yet been described. (10) Pregabalin, like gabapentin, is eliminated unchanged in urine, implying a limited risk of interactions involving cytochrome P450, and suggesting that the dose should be reduced in patients with even moderate renal failure (creatinine clearance below 60 ml/min). (11) In practice, pregabalin offers nothing new for patients with partial epilepsy, for whom several other antiepileptics are available. The few available treatments for neuropathic pain have limited efficacy, and pregabalin may therefore be tried when both tricyclics and gabapentin fail. However, it is in no way certain that pregabalin is effective in such patients, and comparative trials are lacking.
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PMID:Pregabalin: new drug. Very similar to gabapentin. 1639 76

Pregabalin is a recently licensed and marketed antiepileptic drug for use as adjunctive treatment of partial epilepsy. It acts at presynaptic calcium channels, modulating neurotransmitter release in the CNS, properties it shares with gabapentin. Its clinical development over the past decade has included its use in the treatment of neuropathic pain, and generalized anxiety disorder, in addition to epilepsy. Three multi-centre randomised, double-blind, placebo-controlled trials enrolling patients with refractory partial epilepsy have demonstrated an antiepileptic effect of pregabalin against placebo, as adjunctive therapy, with 31-51% of patients showing a 50% reduction in seizure frequency. Adverse effects were dose related, the commonest being somnolence, dizziness, and ataxia. Weight gain was seen in 14% of patients on the highest dose of 600 mg/day. Around 9000 people have been exposed to pregabalin in its development for all indications. No idiosyncratic reactions have been described to date. Pregabalin may be a useful addition in the treatment of refractory partial epilepsy. As with all new AEDs long-term follow up and post marketing surveillance is required.
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PMID:Pregabalin: a new antiepileptic drug for refractory epilepsy. 1641 93

Neuropathic pain is a condition affecting a significant proportion of the world's population. Many therapeutic drugs have been used. They achieve less than satisfactory results and are associated to common side effects that affect the daily life of patients. Pregabalin is a new drug that has been shown to be effective for treating partial epilepsy and peripheral neuropathic pain in clinical trials. It is a structural, but not functional, analogue of GABA. It acts as a ligand of the alpha2-delta subunit, a protein associated to the voltage-dependent calcium channels. Modulation of these channels decreases calcium entry into nerve endings, resulting in a decreased release of several excitatory neurotransmitters. Pregabalin had a linear pharmacokinetics with little variability between the different subjects. It does not bind to plasma proteins, has no liver metabolism, and is excreted trough the kidneys. Few interactions with other drugs may be expected based on these characteristics. In clinical trials, pregabalin has been shown to be effective in postherpetic neuralgia and painful diabetic neuropathy at doses ranging from 150-600 mg/day. The analgesic effects of pregabalin occur in the first few days of treatment and are sustained over time. Side effects are few; most are transient and well-tolerated by patients, and the treatment discontinuation rate is minimal.
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PMID:[Pregabalin. A new treatment for neuropathic pain]. 1652 16

Pregabalin, a compound with a novel mechanism of action (MOA), has demonstrated efficacy as an adjunctive treatment for epilepsy and in several neuropathic pain models. Multiple generalized anxiety disorder (GAD) clinical trials have shown that pregabalin has efficacy similar to the benzodiazepines and venlafaxine. Onset of anxiolytic effect was observed as early as Week 1 of treatment, and efficacy was seen in treating both psychic and somatic anxiety symptoms. Pregabalin binds potently and selectively to the alpha-2-delta subunit of "hyper-excited" voltage-gated calcium channels (VGCCs). The binding of pregabalin to VGCCs changes their conformation, reducing calcium influx at nerve terminals. Pregabalin only modulates the release of excitatory neurotransmitters in "hyper-excited" neurons, restoring them to normal physiological state. This newly defined MOA is believed to confer on pregabalin its anxiolytic, analgesic, and anticonvulsant properties. Thus, pregabalin may offer physicians an effective and well-tolerated therapy for GAD, which differs from existing treatments.
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PMID:Pregabalin: From molecule to medicine. 1676 30

The management of postoperative pain has been greatly informed by an increasing understanding of the basic science of pain transmission. The idea that analgesia given before the injury would be more effective than the same analgesia given after the injury was named pre-emptive analgesia. The evidence for this phenomenon in postoperative pain management has been very mixed. The methodological problems of such studies, and the difficulties of all the major outcome measures make comparison of the studies available difficult. In the 20 years since the concept was proposed there has been a change in anaesthetic practice that in effect incorporates pre-emptive analgesia with opiates. Evidence for any pre-emptive analgesic with non-steroidal anti-inflammatory drugs is very poor, but the use of local anaesthetic blocks continues to be an area of study. Pre-emptive use of analgesic drugs is not the magic bullet to prevent postoperative pain, but is a strategy of use, among others for managing postoperative pain. Protective analgesia is a strategy that has grown out of the same desire to give drugs before injury to reduce the pain experienced afterwards. In this case the drugs under study have not been primary analgesics, but adjuvant drugs used commonly in the non-acute pain arena. In particular, the drug gabapentin, and to a lesser extent its related drug pregabalin. These drugs have been given by mouth as a pre-medicant, 1 hour before surgery in a variety of operations. A recent meta-analysis of the existing literature shows reduction of postoperative morphine consumption but little reduction in reporting of opiate side effects. Pregabalin, which has a better pharmacokinetic profile, may be a better alternative, and is currently under study. Neither gabapentin nor pregabalin are licensed for use in postoperative pain, and it is unlike that the manufacturers will seek such a licence.
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PMID:Pre-emptive analgesia and protective premedication. What is the difference? 1682 28

The aim of this study was to evaluate the tolerability, safety and efficacy of pregabalin in Indian patients with peripheral neuropathic pain. In this prospective, multicenter, non-comparative, open-label study, patients with peripheral neuropathic pain (n = 111) received pregabalin in doses ranging from 75 to 300 mg twice daily for 3 weeks. Primary efficacy measures included weekly pain score and the Visual Analogue Scale (VAS) score of the Short-Form McGill Pain Questionnaire (SF-MPQ). Despite a short study duration, a significant reduction was seen in weekly pain score (p < 0.0001), as well as VAS score of SF-MPQ (p < 0.0001). Significant improvements were also seen in other pain-related endpoints, weekly sleep interference score, quality of life measures, and patient and clinician ratings of global improvement. Pregabalin was well tolerated, and the most common adverse events were dizziness and somnolence. The short study duration precluded the assessment of longer term safety issues such as weight gain. This study has demonstrated the safety, tolerability and efficacy of pregabalin for peripheral neuropathic pain in Indian patients.
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PMID:Pregabalin for peripheral neuropathic pain: results of a multicenter, non-comparative, open-label study in Indian patients. 1693 47


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