Safety and efficacy of pregabalin in patients with central post-stroke pain

Kim, Jong Seung; Bashford, Guy; Murphy, T.K.; Martin, Andrew; Dror, Vardit; Cheung, Raymond

doi:10.1016/j.pain.2010.12.023

Cited by 117 publications

(66 citation statements)

References 29 publications

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“…However, so far no evidence has been provided to support the use of gabapentinoids in the treatment of central neuropathic pain of thalamic damage caused by either ischemic or hemorrhagic stroke. In a 13-week, randomized, doubleblind, multicenter, placebo-controlled trial, treatment with pregabalin did not provide significant pain relief in patients with CPSP [19].…”

Section: Gabapentinoid Insensitivity In Central Neuropathic Pain Of Tmentioning

confidence: 92%

“…In 2004, gabapentinoids were also approved as first-line drugs for the treatment of some types of neuropathic pain, such as painful diabetic neuropathy, post-herpetic neuralgia, and spinal cord injury-induced pain [3,14,15,18]. Nonetheless, gabapentinoids are commonly used to treat other types of In a recent placebo-controlled trial, pregabalin failed to show significant improvement over placebo in patients with CPSP [19]. More recently, we evaluated the anti-allodynic effects of GBP in rats with CPSP hypersensitivity induced by experimental thalamic hemorrhage and found that, although GBP had a dose-dependent anti-allodynic effect following a single systemic administration, the effectiveness was transient, gradually decreasing after repeated administration for 14 days, implying the existence of drug insensitivity [20].…”

Section: Introductionmentioning

confidence: 99%

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Gabapentinoid Insensitivity after Repeated Administration is Associated with Down-Regulation of the α2δ-1 Subunit in Rats with Central Post-Stroke Pain Hypersensitivity

Yang

et al. 2016

Neurosci. Bull.

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The a 2 d-1 subunit of the voltage-gated Ca 2? channel (VGCC) is a molecular target of gabapentin (GBP), which has been used as a first-line drug for the relief of neuropathic pain. GBP exerts its anti-nociceptive effects by disrupting trafficking of the a 2 d-1 subunit to the presynaptic membrane, resulting in decreased neurotransmitter release. We previously showed that GBP has an antiallodynic effect in the first two weeks; but this is followed by insensitivity in the later stage after repeated administration in a rat model of central post-stroke pain (CPSP) hypersensitivity induced by intra-thalamic hemorrhage. To explore the mechanisms underlying GBP insensitivity, the cellular localization and time-course of expression of the a 2 d-1 subunit in both the thalamus and spinal dorsal horn were studied in the same model. We found that the a 2 d-1 subunit was mostly localized in neurons, but not astrocytes and microglia. The level of a 2 d-1 protein increased in the first two weeks after injury but then decreased in the third week, when GBP insensitivity occurred. Furthermore, the a 2 d-1 down-regulation was likely caused by later neuronal loss in the injured thalamus through a mechanism other than apoptosis. In summary, the present results suggest that the GBP receptor a 2 d-1 is mainly expressed in thalamic neurons in which it is up-regulated in the early stage of CPSP but this is followed by dramatic down-regulation, which is likely associated with GBP insensitivity after long-term use.Keywords Central post-stroke pain Á Calcium channel a 2 d subunit Á Gabapentinoid Á Thalamic hemorrhagic stroke Á Thalamus Á Spinal dorsal horn

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Section: Gabapentinoid Insensitivity In Central Neuropathic Pain Of Tmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Gabapentinoid Insensitivity after Repeated Administration is Associated with Down-Regulation of the α2δ-1 Subunit in Rats with Central Post-Stroke Pain Hypersensitivity

Yang

et al. 2016

Neurosci. Bull.

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“…In the clinic, CPSP is usually treated with adjuvant analgesics, such as antidepressants, antiepileptogenics and narcotic analgesics, based on the treatment of neuropathic pain or surgery. 4,[9][10][11][12] However, the effect of adjuvant analgesics on the BCAO-induced pain is unclear.…”

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confidence: 99%

Effects of Adjuvant Analgesics on Cerebral Ischemia-Induced Mechanical Allodynia

Matsuura

Harada

Tokuyama

2016

Biological & Pharmaceutical Bulletin

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Central post-stroke pain (CPSP), a potential sequela of stroke, is classified as neuropathic pain. Although we recently established a CPSP-like model in mice, the effects of adjuvant analgesics as therapeutic drugs for neuropathic pain in this model are unknown. Hence, the aim of the present study was to assess the usefulness of our model by evaluating the effects of adjuvant analgesics used for treating neuropathic pain in this mouse model of CPSP. Male ddY mice were subjected to 30 min of bilateral carotid artery occlusion (BCAO). The development of hind paw mechanical allodynia was measured after BCAO using the von Frey test. The mechanical allodynia was significantly increased on day 3 after BCAO compared with that during the pre-BCAO assessment. BCAO-induced mechanical allodynia was significantly decreased by intraperitoneal injections of imipramine (a tricyclic antidepressant), mexiletine (an antiarrhythmic), gabapentin (an antiepileptic), or a subcutaneous injection of morphine (an opioid receptor agonist) compared with that following vehicle treatment in BCAO-mice. By contrast, milnacipran (a serotonin and norepinephrine reuptake inhibitor), paroxetine (selective serotonin reuptake inhibitor), carbamazepine (antiepileptic), and indomethacin (nonsteroidal anti-inflammatory drug) did not affect the BCAO-induced mechanical allodynia. Our results show that BCAO in mice may be useful as an animal model of CPSP. In addition, BCAO-induced mechanical allodynia may be suppressed by some adjuvant analgesics used to treat neuropathic pain.Key words central post-stroke pain; global ischemia; allodynia; neuropathic pain Pain may occur with actual substantial or even potential histologic lesions, producing uncomfortable sensory and emotional experiences, according to the definition by the International Association for the Study of Pain. One type of pain, neuropathic pain, is caused by dysfunctional peripheral or central nerves and results in the appearance of allodynia and hypersensitivity to pain.1,2) Cerebral stroke patients may experience several types of pain, including musculoskeletal pain, headache, and neuropathic central post-stroke pain (CPSP).Among the different types of neuropathic pain, CPSP is an especially intractable condition to treat. CPSP is associated with various symptoms, such as burning and lancinating pain, and the incidence of CPSP after cerebral stroke is reportedly 1-14%. 3,4) In clinical studies, the risk factors associated with CPSP are the degree of brain infarction, sexual dimorphism, alcohol intake, depression anamnesis, statin use, dyslipidemia, diabetes, and peripheral vascular disorder.5) The pathogenic mechanisms for CPSP and neuropathic pain appear similar at the point of excitation of primary afferent fibers and for epistatic or central excitation or suppression pathway disorders. Recently, we established a CPSP-like animal model by experimentally inducing focal (middle cerebral artery occlusion model) or global cerebral ischemia (bilateral carotid artery occlusion model; BCAO). 6,...

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“…After reviewing the full texts, we deemed 8 English language studies that enrolled 459 patients with CPSP eligible for our review (Table 1). [37][38][39][40][41][42][43][44] There was almost perfect agreement (Φ=0.82) between reviewers at the full-text review stage. All trials evaluated treatment effects on pain, and none reported effects on physical functioning, role functioning, or interpersonal functioning (Figure 2).…”

Section: Resultsmentioning

confidence: 99%

“…One study reported no difference in the number of participants (in the pregabalin and placebo groups) who presented with psychiatric comorbidities, specifically depression and insomnia. 41 Figure 3 portrays the risk of bias assessment.…”

Section: Resultsmentioning

confidence: 99%

Management of Central Poststroke Pain

Mulla

Wang

Khokhar

et al. 2015

Stroke

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C entral poststroke pain (CPSP) is a chronic (≥3 months) neuropathic disorder that can occur after a lesion or disease affecting the central somatosensory system. 1 The pain may be spontaneous, occurring either constantly or intermittently, or evoked in response to external stimuli.1 It may develop immediately after a stroke, or years later. [2][3][4][5] To date, the largest prospective study, which enrolled 15 754 participants with ischemic stroke from 35 countries, found that 2.7% of patients developed CPSP at 1 year after stroke.6 Because CPSP case definition is complex, 1 however, its reported prevalence is variable, and dependent on the site of lesion: 1 study, for instance, found that 25% of patients with brain stem infarcts developed CPSP within 6 months. 4 Individuals with CPSP commonly experience sensory abnormalities, including increased tactile and thermal sensitivities, which impair their quality of life. [7][8][9] The underlying mechanisms of CPSP are poorly understood, 1 contributing to challenges in its management.There are several pharmacological and nonpharmacological therapies available for patients with CPSP; few systematic Background and Purpose-Central poststroke pain is a chronic neuropathic disorder that follows a stroke. Current research on its management is limited, and no review has evaluated all therapies for central poststroke pain. Methods-We conducted a systematic review of randomized controlled trials to evaluate therapies for central poststroke pain. We identified eligible trials, in any language, by systematic searches of AMED, CENTRAL, CINAHL, DARE, EMBASE, HealthSTAR, MEDLINE, and PsychINFO. Eligible trials (1) enrolled ≥10 patients with central poststroke pain; (2) randomly assigned them to an active therapy or a control arm; and (3) collected outcome data ≥14 days after treatment. Pairs of reviewers, independently and in duplicate, screened titles and abstracts of identified citations, reviewed full texts of potentially eligible trials, and extracted information from eligible studies. We used a modified Cochrane tool to evaluate risk of bias of eligible studies, and collected patient-important outcomes according to recommendations by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials. We conducted, when possible, random effects meta-analyses, and evaluated our certainty in treatment effects using the Grading of Recommendations Assessment, Development, and Evaluation System. Results-Eight eligible English language randomized controlled trials (459 patients) tested anticonvulsants, an antidepressant, an opioid antagonist, repetitive transcranial magnetic stimulation, and acupuncture. Results suggested that all therapies had little to no effect on pain and other patient-important outcomes. Our certainty in the treatment estimates ranged from very low to low. Conclusions-Our

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Safety and efficacy of pregabalin in patients with central post-stroke pain

Cited by 117 publications

References 29 publications

Gabapentinoid Insensitivity after Repeated Administration is Associated with Down-Regulation of the α2δ-1 Subunit in Rats with Central Post-Stroke Pain Hypersensitivity

Gabapentinoid Insensitivity after Repeated Administration is Associated with Down-Regulation of the α2δ-1 Subunit in Rats with Central Post-Stroke Pain Hypersensitivity

Effects of Adjuvant Analgesics on Cerebral Ischemia-Induced Mechanical Allodynia

Management of Central Poststroke Pain

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