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-1α (HIF-1α) 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-1α. 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.

Are radio‐contrast agents commonly used in discography toxic to the intact intervertebral disc tissue cells?

“…As a result, the in vitro test results, which are difficult to comply with in vivo conditions, may become even more controversial since the cell does not interact with formations such as extracellular matrix structure. Besides, since the genetic structure of the cells in the cell line has been modified, they will not carry the genotypic and/or phenotypic characteristics that they have in the human body …”

“…In summary, if a drug is administered to a patient and there is another accompanying disease in this patient, the disease may increase the side effects of the administered drug, as it is known that drugs may cause more adverse reactions depending on the food consumption, smoking and alcohol use . Therefore, in this study, we selected the patients, whose tissues were used in the preparation of primary cell cultures, who did not smoke, did not use alcohol or did not use drugs that inhibited the CYP3A4 group.…”

“…When stained with both AO and PI, all live nucleated cells produce green fluorescence, and all dead nucleated cells produce red fluorescence. To prepare the AO/PI stain, 4‐mg AO (dissolved in 2‐mL 99% ETOH), 10‐g sodium‐ethylenediaminetetraacetic acid, 4‐mg PI and 50 mL FBS were mixed well and sterile distilled water was added to reach a 200‐mL final volume …”

Are the intervertebral disc tissue cells damaged when attempting to prevent thrombus formation with dabigatran which is amongst the new oral anticoagulants?

“…Intervertebral disc tissue is avascular and aneuronal, just like cartilage tissue (1,2, [18][19][20]. Due to this anatomical structure, drugs and nutrients pass from neighboring osseous structures through hyaline membranes and accumulate in the outer layers of the intervertebral disc tissue (13,14,17,25,26).…”

“…Due to this anatomical structure, drugs and nutrients pass from neighboring osseous structures through hyaline membranes and accumulate in the outer layers of the intervertebral disc tissue (13,14,17,25,26). Though no pharmacokinetic studies currently exist that examine dabigatran's migration through hyaline membranes and fluid compartment concentrations with high evidential value, it is an indisputable fact that many medicaments, such as synovia, may accumulate in the liquid compartments and/ or on surfaces which come into contact with intervertebral disc tissue, and thus they may pass into other tissues (1,2, 13,14,[17][18][19][20]25,26). Alongside the advancement of pharmaceutical technology and regenerative medicine, many reports have examined how to protect tissues by investigating the toxicity of drugs at the molecular level.…”