Gabapentin (GBP), an antiepileptic drug to treat epilepsy and neuropathic pain, has become an emerging pollutant in aquatic environments. Previous results suggested that GBP can cause a potential toxicity on the heart development of zebrafish but its cardiovascular effects are still not clear. In the current study, zebrafish embryos were exposed to GBP at environmental relevant concentrations (0, 0.1, 10 and 1000 μg/L) to assess its impact on cardiovascular systems during the early life stage of zebrafish. GBP exposure induced an increase in heartbeat rate and blood flow. The development of blood vessels was also affected with the vascular width significantly decreased at 10 μg/L and higher concentration of GBP. GBP exposure led to an abnormal vascular development by inhibiting the expression of relevant genes (flk1, vegfr-3, gata1, vegfα, and vegfr-2). Furthermore, GBP at 0.1 μg/L elevated the levels of reactive oxygen species and antioxidant enzyme. The vascular cell apoptosis was promoted through genes like p53, bad, and bcl2. However, these adverse effects were reversible with the antioxidant N-acetyl-L-cysteine, highlighting the crucial role of oxidative damage in GBP induced vascular toxicity. This research offers new perspectives on the adverse outcome pathways of antiepileptic drugs in non-target aquatic organisms.

BACKGROUND: Gabapentin supplementation may have some potential in pain control after lumbar laminectomy and discectomy, and this meta-analysis aims to explore the impact of gabapentin supplementation on postoperative pain management for lumbar laminectomy and discectomy.
METHODS: PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases were systematically searched, and we included randomized controlled trials assessing the effect of gabapentin supplementation on the pain control of lumbar laminectomy and discectomy.
RESULTS: Five randomized controlled trials were finally included in the meta-analysis. Overall, compared with control intervention for lumbar laminectomy and discectomy, gabapentin supplementation was associated with significantly lower pain scores at 2 hours (MD = -2.75; 95% CI = -3.09 to -2.41; P < .00001), pain scores at 4 hours (MD = -2.28; 95% CI = -3.36 to -1.20; P < .0001), pain scores at 24 hours (MD = -0.70; 95% CI = -0.86 to -0.55; P < .00001) and anxiety score compared to control intervention (MD = -1.32; 95% CI = -1.53 to -1.11; P < .00001), but showed no obvious impact on pain scores at 12 hours (MD = -0.58; 95% CI = -1.39 to 0.22; P = .16). In addition, gabapentin supplementation could significantly decrease the incidence of vomiting in relative to control intervention (OR = 0.31; 95% CI = 0.12-0.81; P = .02), but they had similar incidence of nausea (OR = 0.51; 95% CI = 0.15-1.73; P = .28).
CONCLUSIONS: Gabapentin supplementation benefits to pain control after lumbar laminectomy and discectomy.

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 efficacy and safety of pulsed radiofrequency of the dorsal root ganglion combined with ozone injection for treating acute herpes zoster (HZ) neuralgia in middle-aged and elderly adults.
METHODS: A total of 164 middle-aged and elderly patients with acute HZ were randomly assigned to 2 groups: the pulsed radiofrequency combined with ozone injection group (group A) and the pulsed radiofrequency group (group B). The therapeutic effects were evaluated using Numeric Rating Scale (NRS) scores and the average doses of gabapentin (mg/d) preoperatively and 1 day, 2 weeks, 4 weeks, 12 weeks, and 24 weeks postoperatively. The incidence of clinically significant postherpetic neuralgia (PHN) and complications in the 2 groups were recorded.
RESULTS: The data showed that the NRS scores and the doses of gabapentin after treatment were significantly lower when compared with the baseline values in both groups. Compared with group B, the NRS scores and the doses of postoperative gabapentin were significantly lower in group A. The incidence of PHN was significantly lower at weeks 4, 12, and 24 in group A than in group B. No adverse reactions occurred in either of the 2 groups post-treatment.
CONCLUSIONS: The results indicated that ozone injection in the dorsal root ganglion combined with pulsed radiofrequency therapy was more effective in treating acute HZ neuralgia in middle-aged and elderly adults. It provides patients with longer-lasting pain relief, decreased incidence of PHN and the doses of medication, and improved quality of life than with Pulsed Radiofrequency treatment.

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.

OBJECTIVE: Inflammation regulates ventricular remodeling after myocardial infarction (MI), and gabapentin exerts anti-inflammatory effects. We investigated the anti-inflammatory role and mechanism of gabapentin after MI.
METHODS: Rats were divided into the sham group (n = 12), MI group (n = 20), and MI + gabapentin group (n = 16). MI was induced by left coronary artery ligation. The effects of gabapentin on THP-1-derived macrophages were examined in vitro.
RESULTS: In vivo, 1 week after MI, gabapentin significantly reduced inducible nitric oxide synthase (iNOS; M1 macrophage marker) expression and decreased pro-inflammatory factors (tumor necrosis factor [TNF]-α and interleukin [IL]-1β). Gabapentin upregulated the M2 macrophage marker arginase-1, as well as CD163 expression, and increased the expression of anti-inflammatory factors, including chitinase-like 3, IL-10, and transforming growth factor-β. Four weeks after MI, cardiac function, infarct size, and cardiac fibrosis improved after gabapentin treatment. Gabapentin inhibited sympathetic nerve activity and decreased ventricular electrical instability in rats after MI. Tyrosine hydroxylase and growth-associated protein 43 were suppressed after gabapentin treatment. Gabapentin downregulated nerve growth factor (NGF) and reduced pro-inflammatory factors (iNOS, TNF-α, and IL-1β). In vitro, gabapentin reduced NGF, iNOS, TNF-α, and IL-1β expression in lipopolysaccharide-stimulated macrophages. Mechanistic studies revealed that the peroxisome proliferator-activated receptor-γ antagonist GW9662 attenuated the effects of gabapentin. Moreover, gabapentin reduced α2δ1 expression in the macrophage plasma membrane and reduced the calcium content of macrophages.
CONCLUSIONS: Gabapentin attenuates cardiac remodeling by inhibiting inflammation via peroxisome proliferator-activated receptor-γ activation and preventing calcium overload.

BACKGROUND: Peripheral neuropathic pain (NeP), induced by surgical intervention, is a well-known complication or sequela that remains a clinical challenge with few effective treatments. Ideal animal models that can recapitulate surgery-associated NeP remain to be established for both mechanistic studies and drug discovery.
OBJECTIVE: We aimed to establish a new rat model of postsurgical NeP and describe its characteristics, as well as screen-promising therapeutic analgesics.
METHODS: Experimental research in rats.
METHODS: The research took place in the laboratory of Xinqiao Hospital of the Third Military Medical University.
METHODS: To mimic the surgical procedure associated with peripheral nerve injury (PNI), we established a transient compression injury (TCI) in the sciatic nerve. Behavioral tests of nociception were used to confirm the effect and the time course of this pain model. Histological assessments (transmission electron microscopy evaluation and immunohistochemistry) were performed to observe the neuropathological and immunological features. RNA sequencing (RNA-seq) of injured nerves and dorsal root ganglia (DRGs) was conducted to reveal the underlying mechanism in the newly established animal model and screen promising therapeutic targets.
RESULTS: We established a rat model of TCI of the PN and detected nociceptive hypersensitivity of the injured (ipsilateral) nerve by behavioral tests. This animal model of NeP was further confirmed by observing time-dependent changes in mechanical allodynia and thermal hyperalgesia, as well as by examining the activation of microglia in the ipsilateral spinal dorsal horn. Pathophysiologically, TCI induced macroscopic nerve swelling and demyelination, which resulted in inflammatory responses in ipsilateral nerves. We also found inflammatory cell infiltration in the ipsilateral nerve that was sustained for several weeks, which further exacerbated local inflammation and oxidative stress. Moreover, RNA-seq revealed remarkably upregulated inflammatory reactions in PNs and the DRGs. Notably, the overexpression of inflammatory mediators and the infiltration of macrophages and microglia triggered remote immune responses in DRGs. Based on the RNA-seq results, we also confirmed that gabapentin (GBP) exerts therapeutic effects in TCI-induced NeP by regulating alpha2delta-1.
CONCLUSIONS: We did not compare the new rat model with the classical pain model (like chronic constriction injury or spared nerve injury) in histology or transcriptomics.
CONCLUSIONS: We established a new rat model of NeP and thoroughly characterized neuroinflammation in the injured nerve and DRGs. Based on the upregulated genes in DRGs in this model, we screened a promising analgesic (GBP) capable of reducing pain hypersensitivity in surgery-associated NeP.

Epoxyeicosatrienoic acids with anti-inflammatory effects are inactivated by soluble epoxide hydrolase (sEH). Both sEH and histone deacetylase 6 (HDAC6) inhibitors are being developed as neuropathic pain relieving agents. Based on the structural similarity, we designed a new group of compounds with inhibition of both HDAC6 and sEH and obtained compound M9. M9 exhibits selective inhibition of HDAC6 over class I HDACs in cells. M9 shows good microsomal stability, moderate plasma protein binding rate, and oral bioavailability. M9 exhibited a strong analgesic effect in vivo, and its analgesic tolerance was better than gabapentin. M9 improved the survival time of mice treated with lipopolysaccharide (LPS) and reversed the levels of inflammatory factors induced by LPS in mouse plasma. M9 represents the first sEH/HDAC6 dual inhibitors with in vivo antineuropathic pain and anti-inflammation.

UNASSIGNED: Neuropathic corneal pain (NCP) is a new and ill-defined disease characterized by pain, discomfort, aching, burning sensation, irritation, dryness, and grittiness. However, the mechanism underlying NCP remain unclear. Here, we reported a novel rat model of primary NCP induced by long ciliary nerve (LCN) ligation. After sustained LCN ligation, the rats developed increased corneal mechanical and chemical sensitivity, spontaneous blinking, and photophobia, which were ameliorated by intraperitoneal injection of morphine or gabapentin. However, neither tear reduction nor corneal injury was observed in LCN-ligated rats. Furthermore, after LCN ligation, the rats displayed a significant reduction in corneal nerve density, as well as increased tortuosity and beading nerve ending. Long ciliary nerve ligation also notably elevated corneal responsiveness under resting or menthol-stimulated conditions. At a cellular level, we observed that LCN ligation increased calcitonin gene-related peptide (neuropeptide)-positive cells in the trigeminal ganglion (TG). At a molecular level, upregulated mRNA levels of ion channels Piezo2, TRPM8, and TRPV1, as well as inflammatory factors TNF-α, IL-1β, and IL-6, were also detected in the TG after LCN ligation. Meanwhile, consecutive oral gabapentin attenuated LCN ligation-induced corneal hyperalgesia and increased levels of ion channels and inflammation factors in TG. This study provides a reliable primary NCP model induced by LCN ligation in rats using a simple, minimally invasive surgery technique, which may help shed light on the underlying cellular and molecular bases of NCP and aid in developing a new treatment for the disease.

This investigation aims to evaluate the effectiveness of the paravertebral injection of recombinant human interferon-α2b in conjunction with high-voltage, long-term, pulsed radiofrequency (PRF) in the dorsal root ganglion for the mitigation of postherpetic neuralgia (PHN).
This retrospective study included 84 individuals with acute PHN. The participants were divided into 3 groups. Group H was treated with interferon-α2b combined with high-voltage long-term PRF. Group C was treated with a combination of high-voltage, long-term PRF and a paravertebral injection (without recombinant human interferon-α2b), and group I was treated with interferon-α2b only. All the patients in the 3 groups were orally administered a 5-mg morphine hydrochloride quick-release tablet when a burst of pain occurred during treatment. The numerical rating scale for pain score, the interleukin-6 and galectin-3 levels, and the incidence of PHN were documented before and after therapy.
The pain intensity of all individuals decreased after therapy. Compared with group C, the numerical rating scale scores for group H were significantly reduced at 4, 8, and 12 weeks following therapy, and the PHN incidence was significantly lower. Compared with prior treatment, the recommended dosage of gabapentin capsules and immediate-release morphine hydrochloride tablets was reduced for group H. Compared with group C, the requirement for orally administrated gabapentin capsules and morphine hydrochloride tablets in group H was reduced significantly after treatment. No serious adverse reactions occurred in any of the 3 groups.
Within the context of treatment of acute PHN, the injection of interferon-α2b in conjunction with high-voltage, long-term application of PRF is more effective than PRF or the injection of interferon-α2b alone.