Pregabalin is a prescription medicine that has recently been approved for individuals who suffer from fibromyalgia, neuropathic pain, anxiety disorder, or epilepsy. Pregabalin has the side effects of dizziness, sleepiness, and angioedema. Pregabalin-induced rhabdomyolysis has been rarely reported, with only four reports to date. We report two cases of rhabdomyolysis after pregabalin treatment. A man aged older than 90 years presented with exhaustion, muscle aches, and a high serum creatine kinase concentration after taking 75 mg of pregabalin on the first day of treatment. A woman in her 90s with long-term use of pregabalin presented with considerably elevated serum creatine kinase concentrations. Both patients had a long history of taking statins. Pregabalin therapy was stopped, high-volume intravenous fluids were administered, and serum electrolytes were frequently checked. Alkalinisation was performed with excellent outcomes. The Naranjo Adverse Drug Reaction scale and previous research suggest an association between pregabalin and rhabdomyolysis. Clinicians should be alert to the possibility of rhabdomyolysis occurring with the use of pregabalin, especially when taking statins.

Pain is a common public health problem and remains as an unmet medical need. Currently available analgesics usually have limited efficacy or are accompanied by many adverse side effects. To achieve satisfactory pain relief by multimodal analgesia, new combinations of nefopam and gabapentinoids (pregabalin/gabapentin) were designed and assessed in inflammatory, osteoarthritis and neuropathic pain. Isobolographic analysis was performed to analyze the interactions between nefopam and gabapentinoids in carrageenan-induced inflammatory pain, mono-iodoacetate-induced osteoarthritis pain and paclitaxel-induced peripheral neuropathic pain in mice. The anti-inflammatory effect and motor performance of monotherapy or their combinations were evaluated in the carrageenan-induced inflammatory responses and rotarod test, respectively. Nefopam (1, 3, 5, 10, 30 mg/kg, p.o.), pregabalin (3, 6, 12, 24 mg/kg, p.o.) or gabapentin (25, 50, 75, 100 mg/kg, p.o.) dose-dependently reversed mechanical allodynia in three pain models. Isobolographic analysis indicated that the combinations of nefopam and gabapentinoids exerted synergistic anti-nociceptive effects in inflammatory, osteoarthritis, and neuropathic pain mouse models, as evidenced by the experimental ED50 (median effective dose) falling below the predicted additive line. Moreover, the combination of nefopam-pregabalin/gabapentin alleviated carrageenan-induced inflammation and edema, and also prevented gabapentinoids-related sedation or ataxia by lowering their effective doses. Collectively, the co-administration of nefopam and gabapentinoids showed synergistic analgesic effects and may result in improved therapeutic benefits for treating pain.

OBJECTIVE: To investigate the effect of three different doses of oral pregabalin on minimum alveolar concentration of isoflurane (MACISO) in cats.
METHODS: Prospective, randomized, placebo-controlled, blinded, crossover trial.
METHODS: A group of eight healthy adult cats aged 24-48 months.
METHODS: Cats were randomly assigned to three oral doses of pregabalin (low dose: 2.5 mg kg-1, medium dose: 5 mg kg-1, high dose: 10 mg kg-1) or placebo 2 hours before MACISO determination, with the multiple treatments administered with a minimum 7 day washout period. Anesthesia was induced and maintained with isoflurane in oxygen until endotracheal intubation was achieved, and maintained with isoflurane with volume-controlled ventilation. MACISO was determined in triplicate using the bracketing technique and tail clamp method 120 minutes after pregabalin or placebo administration. Physiologic variables (including heart rate and blood pressure) recorded during MACISO determination were averaged and compared between the pregabalin and placebo treatments. One-way analysis of variance and the Friedman test were used to assess the difference for normally and non-normally distributed data, respectively. The Tukey test was used as a post hoc analysis. Values of p < 0.05 were considered significant.
RESULTS: The MACISO with the medium- and high-dose pregabalin treatments were 1.33 ± 0.21% and 1.23 ± 0.17%, respectively. These were significantly lower than MACISO after placebo treatment (1.62 ± 0.13%; p = 0.014, p < 0.001, respectively), representing a decrease of 18 ± 9% and 24 ± 6%. The mean plasma pregabalin concentration was negatively correlated with MACISO values. Physiologic variables did not differ significantly between treatments.
CONCLUSIONS: Doses of 5 or 10 mg kg-1 pregabalin, administered orally 2 hours before determining MACISO, had a significant isoflurane-sparing effect in cats.

OBJECTIVE: This study aimed to systematically evaluate the clinical efficacy of gabapentin and pregabalin in the treatment of acute herpes zoster (HZ) neuralgia, including pain control and the occurrence of adverse effects.
METHODS: A systematic computerized search was conducted in October 2023 in PubMed, Embase, Web of Science, Cochrane Library, VIP, CNKI, and Wanfang databases. Data from randomized controlled trials (RCTs) comparing gabapentin analogs for the treatment of acute HZ neuralgia were searched. Endpoints were visual analog scores (Visual Analog Scale) and adverse effects at 1, 2, and 4 weeks. Data from studies that met the inclusion criteria were extracted for meta-analysis and sensitivity analysis using Revman 5.4 and Stata16.
RESULTS: The study included 292 patients from 6 RCTs. Of these, 118 were in the gabapentin-treated group, 37 were in the pregabalin-treated group, and 137 were in the placebo-controlled group. The gabapentin group showed superior pain reduction compared with the placebo group ( P < 0.05), but adverse events were more frequent.
CONCLUSIONS: Gabapentin can effectively reduce acute HZ neuralgia in patients. Pregabalin requires additional RCTs to supplement the analysis.

Diabetic peripheral neuropathic pain (DPNP) and postherpetic neuralgia (PHN) are challenging and often intractable complex medical conditions, with a substantial impact on the quality of life. Mirogabalin, a novel voltage-gated Ca2+ channel α2δ ligand, was approved for the indication of DPNP and PHN. However, the time course of effects has not yet been clarified.We aimed to establish pharmacodynamic and placebo effect models of mirogabalin and pregabalin in DPNP and PHN, and to quantitatively compare the efficacy characteristics (maximum efficacy, onset time, and other pharmacodynamic parameters) and safety of mirogabalin and pregabalin. Public databases were comprehensively searched for randomized placebo-controlled clinical trials. A model-based meta-analysis (MBMA) was developed to describe the time course of drug efficacy and placebo effects. Adverse events were compared using a fixed-effects meta-analysis. Sixteen studies including 5,147 participants were eligible for this study. The placebo effect was relatively high and gradually increased with time, and it required at least eight weeks to reach a plateau. The pharmacodynamic model revealed that the maximum pure efficacy for mirogabalin and pregabalin was approximately -7.85 % and -8.86 %, respectively; the efficacy of mirogabalin to relieve DPNP and PHN was not superior to that of pregabalin, and both drugs had similar safety. While the rate constant of the onset rate of pregabalin was approximately thrice as high as that of mirogabalin. In addition, the baseline level of pain was an important factor affecting pregabalin efficacy. These findings are helpful in evaluating the clinical extension value of mirogabalin. They suggest that the high placebo effect and the baseline level of pain should be considered when grouping patients in future research and development of voltage-gated Ca2+ channel neuroanalgesic.

Pregabalin is the first-line treatment for neuropathic pain. Cases of cutaneous hypersensitivity reactions caused by pregabalin generally occur within 2 weeks of initiating medication. We report a rare case of a delayed cutaneous hypersensitivity reaction caused by pregabalin, which was confirmed by a drug provocation test. A 72-year-old man with severe herpes zoster neuralgia developed maculopapular drug eruption covering 80% to 90% of his total body surface area after 40 days of combined multidrug analgesia. A drug provocation test for pregabalin was positive. The time interval between initiating medication and the onset of the patient\'s rash was the longest and he also had the largest area of skin affected compared with patients with a similar condition in previous related reports. Remaining vigilant for possible adverse cutaneous hypersensitivity reactions during treatment is important because of the long-term course of pregabalin treatment for neuropathic pain.

This study aims to clarify the effects of dihydroartemisinin(DHA) combined with pregabalin(PGB) on neuropathic pain(NP) in mice and explore the neuroinflammatory regulatory mechanism. NP mice model was established using spinal nerve ligation, whereas the sham group exposed the spinal nerve without ligation. The mice were randomly divided into sham group, model group, PGB groups of low, medium, and high doses(PGB-L, PGB-M, and PGB-H, with 22, 45, and 91 mg·kg~(-1)), DHA group(16 mg·kg~(-1)), and DHA combined with PGB groups of low, medium, and high doses(DHA + PGB-L, DHA + PGB-M, and DHA + PGB-H). Administration by gavage 18 days after modeling. Von Frey and cold plate were used to detect mechanical pain threshold and cold pain sensitivity in mice. The tail suspension test and forced swimming test were used to investigate depressive behavior, and the open field test was used to estimate anxiety behavior. The Morris water maze was used to evaluate cognitive function. Liquid suspension chip technology was used to quantitatively analyze immune inflammation-related factors. Immunofluorescence was used to detect the expression of CC chemokine ligand 3(CCL3) and transmembrane protein 119(TMEM119). The results showed that compared with the sham group, the mechanical pain and cold pain sensitivity thresholds of the model group were significantly reduced, and the struggle time was significantly increased in the tail suspension test and forced swimming test. The activity time in the central area was significantly reduced in the open field test. The residence time in the second/fourth quadrant was significantly longer than that in other quadrants, and the latency time of platform climbing significantly increased after platform withdrawal in the Morris water maze experiment. The expression of CCL3 was significantly increased; the number of TMEM119 positive cells and the cell body area were significantly increased. Compared with the model group, the DHA + PGB-M group showed a significant increase in mechanical pain and cold pain sensitivity thresholds, as well as a significant increase in struggle time in the tail suspension test and forced swimming test. The activity time in the central area of the open field test was significantly reduced. The residence time in the second/fourth quadrant was significantly shorter than that in other quadrants, and the latency time of platform climbing after platform withdrawal was significantly reduced. Compared with the PGB-M group, the mechanical pain threshold of D14-17 in the DHA + PGB-M group was significantly increased, and the struggle time during forced swimming was significantly increased. The residence time in the second/fourth quadrant of the Morris water maze was significantly shorter than that in other quadrants. Compared with the model group, the expression of CCL3, the number of TMEM119 positive cells, and the cell body area in the DHA + PGB-M group were significantly decreased. This study indicates that DHA + PGB can enhance the analgesic effect of PGB on NP mice, break through the limitations of PGB tolerance, and make up for the shortcomings of PGB in antidepressant and cognitive improvement. Its mechanism may be related to regulating neuroinflammation by inhibiting the activation of microglial cells and expression of CCL3.

UNASSIGNED: To compare the efficacy and safety of pregabalin and carbamazepine in patients with central post-stroke pain (CPSP).
UNASSIGNED: Patients included in the study were randomly assigned to either flexible-dose pregabalin treatment group or carbamazepine treatment group. The primary efficacy variable was face visual analog scale (F-VAS), the second efficacy assessment was used to assess the effect of treatment on mental health by Hamilton anxiety scale (HAMA) and Hamilton depression scale (HAMD).
UNASSIGNED: The mean baseline pain score F-VAS was 6.47 in the pregabalin group and 6.58 in carbamazepine treatment group. F-VAS was significantly lower in the pregabalin group (1.64) than (3.94) carbamazepine treatment group after treatment. Pregabalin was significantly superior to carbamazepine in endpoint assessments on the HAMA and HAMD after treatment. F-VAS and HAMD were showed efficacy as early as week 2 and maintained for whole duration of the study. The average pregabalin dose in the 12-week study was 214.6 (150-375) mg/day. The mean dose (range) of carbamazepine received by the patients was 275.0 (200-400) mg/day. Mild or moderate, typically transient, somnolence and dizziness were the most common adverse events (AES). The differences of the side effects between the two groups were not significant.
UNASSIGNED: Pregabalin, but not carbamazepine, may be effective in improving F-VAS, HAMA and HAMD in patients with CPSP.

BACKGROUND: Pregabalin may have some potential in alleviating pain after thoracic surgery, and this meta-analysis aims to explore the impact of pregabalin on pain intensity for patients undergoing thoracic surgery.
METHODS: PubMed, EMbase, Web of science, EBSCO and Cochrane library databases were systematically searched, and we included randomized controlled trials (RCTs) assessing the effect of pregabalin on pain intensity after thoracic surgery.
RESULTS: Five RCTs were finally included in the meta-analysis. Overall, compared with control intervention for thoracic surgery, pregabalin was associated with significantly reduced pain scores at 0 h (mean difference [MD]=-0.70; 95% confidence interval [CI]=-1.10 to -0.30; P = 0.0005), pain scores at 24 h (MD=-0.47; 95% CI=-0.75 to -0.18; P = 0.001) and neuropathic pain (odd ratio [OR] = 0.24; 95% CI = 0.12 to 0.47; P < 0.0001), but demonstrated no obvious impact on the incidence of dizziness (OR = 1.07; 95% CI = 0.15 to 7.46; P = 0.95), headache (OR = 1.00; 95% CI = 0.30 to 3.35; P = 1.00) or nausea (OR = 1.24; 95% CI = 0.46 to 3.35; P = 0.68).
CONCLUSIONS: Pregabalin may be effective to alleviate the pain after thoracic surgery.

BACKGROUND: Delayed or missed doses are inevitable in epilepsy pharmacotherapy. The current remedial measures recommended by the United States Food and Drug Administration (FDA) for non-adherence are generic and lack clinical evidence.
OBJECTIVE: To assess remedial strategies for delayed or missed pregabalin doses in patients with epilepsy using Monte Carlo simulations.
METHODS: Monte Carlo simulations were performed using a published population pharmacokinetic model for pregabalin. The applicability of five proposed remedial regimens as well as FDA recommendations was evaluated by simulating various poor adherence scenarios in eight populations, including those with renal dysfunction.
RESULTS: All proposed remedial strategies were associated with delay duration and renal function. When delays are relatively short, an immediate regular dose is advised. The cut-off time points for taking the regular dose as a remedial regimen were 1, 2, 4, and 12 h for patients with mild renal impairment and normal renal function, moderate renal impairment, severe renal impairment, and end-stage renal disease, respectively. However, when delay aligns closely with a dosing interval, a regular dose combined with a partial dose proves effective. Generally, supplementing 1.3-fold the regular dose at the next scheduled time adequately compensates for the missed dose.
CONCLUSIONS: Model-based simulations provided quantitative evidence for the effectiveness and feasibility of remedial strategies for missed or delayed pregabalin doses.