A systematic review and meta-analysis of pregabalin preclinical studies

Abstract

Despite large efforts to test analgesics in animal models, only a handful of new pain drugs have shown efficacy in patients. Here, we report a systematic review and meta-analysis of preclinical studies of the commercially successful drug pregabalin. Our primary objective was to describe design characteristics and outcomes of studies testing the efficacy of pregabalin in behavioral models of pain. Secondarily, we examined the relationship between design characteristics and effect sizes. We queried MEDLINE, Embase, and BIOSIS to identify all animal studies testing the efficacy of pregabalin published before January 2018 and recorded experimental design elements addressing threats to validity and all necessary data for calculating effect sizes, expressed as the percentage of maximum possible effect. We identified 204 studies (531 experiments) assessing the efficacy of pregabalin in behavioral models of pain. The analgesic effect of pregabalin was consistently robust across every etiology/measure tested, even for pain conditions that have not responded to pregabalin in patients. Experiments did not generally report using design elements aimed at reducing threats to validity, and analgesic activity was typically tested in a small number of model systems. However, we were unable to show any clear relationships between preclinical design characteristics and effect sizes. Our findings suggest opportunities for improving the design and reporting of preclinical studies in pain. They also suggest that factors other than those explored in this study may be more important for explaining the discordance between outcomes in animal models of pain and those in clinical trials.

Pregabalin does not decrease acute pain or postoperative nausea and vomiting after hysterectomy: a meta-analysis

“…Pregabalin is a structural analog of the inhibitory neurotransmitter gammaaminobutyric acid and the main treatment for neuropathic pain. Its analgesic effect differs from that of other analgesics, including morphine, 7 nonsteroidal antiinflammatory drugs, 8 and morphine-like drugs. 9 Previous studies showed that pregabalin could downregulate visceral hyperalgesia, in addition to reducing the severity of basic pain.…”

The influence of aging and duration of nerve injury on the antiallodynic efficacy of analgesics in laboratory mice

“… 4 By contrast, such treatments are highly effective in preclinical experiments. For example, a recent meta-analysis of all pregabalin experiments in rodents showed an average analgesic response of 71% of the maximum possible effect (such that the majority of animals demonstrated a >50% decrease in pain), 3 whereas clinically pregabalin has a number needed-to-treat of 4.5 against neuropathic pain (such that less than 25% of patients who would not have responded to placebo would show a >50% decrease in pain). 4 It has never been directly evaluated whether part of the reason for this arguably poor translation lies with organismic factors such as age or duration of injury before the analgesic is administered.…”

Controlled activation of cortical astrocytes can reverse neuropathic chronic pain

“…However, it should be recognized that our current study only used young male mice, many pain phenotypes differ between sexes with females typically reporting greater pain responses 32,33 . A further limitation of our study regards translating efficacy from a single pain model in one mouse strain to humans; for example, pregabalin has larger and broader analgesic effects in rodent chronic pain models than observed clinically 34 .…”