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Pregabalin treatment for neuropathic pain may damage intervertebral disc tissue.

ABSTRACT: The aim of the present study was to determine whether pharmaceutical preparations with pregabalin (PGB) as an active ingredient, which are widely prescribed by clinicians, exert toxic effects on human primary nucleus pulposus (NP) and annulus fibrosis (AF). Primary human cell cultures were obtained from intact (n=6) and degenerated (n=6) tissues resected from the two groups of patients. Different doses of PGB were applied to these cultures and cells were subjected to molecular analyses at 0, 24 and 48 h. Cell vitality, toxicity and proliferation were assessed using a spectrophotometer. The expression of chondroadherin (CHAD), a (member of the NP-specific protein family), hypoxia-inducible factor-1? (HIF-1?) and type II collagen (COL2A1) was measured using reverse transcription-quantitative polymerase chain reaction. The results revealed that cell intensity increased in a time-dependent manner and cell vitality continued in the cultures without pharmaceuticals. Cell proliferation was suppressed in the PGB-treated cultures independent from the dose and duration of application. PGB was demonstrated to suppress the expression of CHAD and HIF-1?. In contrast, COL2A1 gene expression was not revealed in any experimental group. The present study utilized an in vitro model and the PGB active ingredient used herein may not be representative of clinical applications; however, the results demonstrated that PGB has a toxic effect on NP/AF cell cultures containing primary human intervertebral disc tissue. In summary, the use of pharmacological agents containing PGB may suppress the proliferation and differentiation of NP/AF cells and/or tissues, which should be considered when deciding on an appropriate treatment regime.

SUBMITTER: Karaarslan N

PROVIDER: S-EPMC6090477 | biostudies-other | 2018 Aug

REPOSITORIES: biostudies-other

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Pregabalin treatment for neuropathic pain may damage intervertebral disc tissue.

Karaarslan Numan N Yilmaz Ibrahim I Sirin Duygu Yasar DY Ozbek Hanefi H Kaplan Necati N Kaya Yasin Emre YE Akyuva Yener Y Gurbuz Mehmet Sabri MS Oznam Kadir K Ates Ozkan O

Experimental and therapeutic medicine 20180612 2

The aim of the present study was to determine whether pharmaceutical preparations with pregabalin (PGB) as an active ingredient, which are widely prescribed by clinicians, exert toxic effects on human primary nucleus pulposus (NP) and annulus fibrosis (AF). Primary human cell cultures were obtained from intact (n=6) and degenerated (n=6) tissues resected from the two groups of patients. Different doses of PGB were applied to these cultures and cells were subjected to molecular analyses at 0, 24 ...[more]

PMID: 30112057

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Project description:PurposeAlthough analyses of pooled clinical trial data have reported how international populations respond to pregabalin by baseline neuropathic pain (NeP) severity, no studies have evaluated this specifically in patients from Japan. Thus, this post hoc pooled analysis evaluated the efficacy of pregabalin in Japanese subjects for treating moderate or severe baseline NeP.Patients and methodsData were pooled from three placebo-controlled trials enrolling Japanese subjects with postherpetic neuralgia (PHN), diabetic peripheral neuropathy (DPN), and spinal cord injury (SCI). The efficacy of pregabalin was evaluated by baseline pain severity (moderate or severe NeP). The trials on PHN and DPN included a 1-week titration of pregabalin from 150 mg/day to 300 or 600 mg/day; the SCI trial included a 4-week dose optimization phase (150 mg/day, titrated up to 600 mg/day). Treatment durations were 13-16 weeks (excluding 1-week taper periods), and pregabalin was administered in two divided doses per day.ResultsMean baseline pain scores and demographic characteristics were comparable between treatment cohorts. Pregabalin treatment significantly reduced pain scores from baseline to endpoint compared with placebo in subjects with both moderate (P<0.001) and severe (P<0.05) baseline pain. Significant improvements in mean sleep scores from baseline to endpoint were associated with pregabalin compared with placebo in subjects with both moderate and severe baseline pain (both P<0.0001). A greater proportion of subjects in both pain cohorts achieved a ≥30% reduction in pain from baseline with pregabalin vs placebo (P<0.05). Higher proportions of pregabalin-treated vs placebo-treated subjects shifted to a less severe pain category at endpoint. Consistent with the known safety profile of pregabalin, common adverse events included dizziness, somnolence, weight gain, and peripheral edema.ConclusionPregabalin demonstrated efficacy for pain relief and sleep improvement with a consistent safety profile in Japanese subjects with either moderate or severe baseline pain severity.Clinicaltrialsgov identifiersNCT0039490130, NCT0055347522, NCT0040774524.

Project description:BackgroundPregabalin is a drug used to treat neuropathic pain, and its use has increased substantially since 2007. Early trials found a strong treatment effect on pain for post-herpetic neuralgia and diabetic neuropathy. However more recent studies have failed to replicate these results.MethodsThis meta-epidemiological study aimed to assess change in the reported effectiveness of pregabalin in neuropathic pain trials over time, and if a change is present, determine any associated factors.Data sourcesWe performed electronic searches for published trials in Medline, Embase and Cochrane Central Register of Controlled Trials databases; and unpublished trials on ClinicalTrials.gov, the EU Clinical Trials Register, and the Australia New Zealand Clinical Trials Registry with no restrictions.Study selectionWe included randomized, placebo-controlled trials of pregabalin for treatment of neuropathic pain in adults.Data extraction and synthesisTwo authors independently extracted study data: sample size and mean baseline, end-point and change in pain scores with measures of variance, trial end year, publication year, clinical indication, funding source, country of study, treatment duration, treatment dose, mean age and percentage male.Primary outcome measureWe defined treatment effect as the mean difference in pain scores between pregabalin and placebo groups at trial end-point and assessed for change over time using a random-effects meta-regression, adjusted for sample size, indication, treatment duration (weeks) and treatment dose.ResultsWe included 38 randomized published trials (9038 participants) and found that between 2003 and 2020, the reported treatment effect of pregabalin decreased by 0.4 points (95% CI: 0.3 to 0.6; p<0.001) on an 11-point pain scale per 5-year interval, from 1.3 points (95% CI: 1.0 to 1.5) in trials conducted in 2001-2005, to 0.3 (95% CI: -0.1 to 0.7) in trials conducted in 2016-2020. The reported treatment effect was lower than the minimal clinically important difference (MCID) of 1.7 points across all time periods, doses and most indications and was not found to be associated with study characteristics.ConclusionsThe reported treatment effect or analgesic efficacy of pregabalin from clinical trials has diminished over time. Clinical recommendations may need to be re-evaluated to account for recent evidence and to consider whether pregabalin therapy is indicated.

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Pregabalin treatment for neuropathic pain may damage intervertebral disc tissue.

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Pregabalin treatment for neuropathic pain may damage intervertebral disc tissue.

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