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Reports of misuse of gabapentin and risks for respiratory depression with concomitant use of gabapentin and opioids have led some states to restrict gabapentin's use and availability. The authors contend that these restrictions are misplaced and could hinder treatment options for patients with chronic pain. [ABSTRACT FROM AUTHOR]

The article discusses a randomized study comparing the efficacy and safety of pregabalin versus gabapentin in chronic pruritus patients. Chronic pruritus, a persistent itching sensation lasting over 6 weeks, significantly impacts physical, psychological, and social well-being. The study found that pregabalin significantly improved chronic pruritus compared to gabapentin, with both drugs being safe and tolerable. Future research should explore long-term effects and conduct health economic analyses for cost-effectiveness. [Extracted from the article]

Gliomas synaptically integrate into neural circuits1,2. Previous research has demonstrated bidirectional interactions between neurons and glioma cells, with neuronal activity driving glioma growth1-4 and gliomas increasing neuronal excitability2,5-8. Here we sought to determine how glioma-induced neuronal changes influence neural circuits underlying cognition and whether these interactions influence patient survival. Using intracranial brain recordings during lexical retrieval language tasks in awake humans together with site-specific tumour tissue biopsies and cell biology experiments, we find that gliomas remodel functional neural circuitry such that task-relevant neural responses activate tumour-infiltrated cortex well beyond the cortical regions that are normally recruited in the healthy brain. Site-directed biopsies from regions within the tumour that exhibit high functional connectivity between the tumour and the rest of the brain are enriched for a glioblastoma subpopulation that exhibits a distinct synaptogenic and neuronotrophic phenotype. Tumour cells from functionally connected regions secrete the synaptogenic factor thrombospondin-1, which contributes to the differential neuron-glioma interactions observed in functionally connected tumour regions compared with tumour regions with less functional connectivity. Pharmacological inhibition of thrombospondin-1 using the FDA-approved drug gabapentin decreases glioblastoma proliferation. The degree of functional connectivity between glioblastoma and the normal brain negatively affects both patient survival and performance in language tasks. These data demonstrate that high-grade gliomas functionally remodel neural circuits in the human brain, which both promotes tumour progression and impairs cognition.

Gabapentinoids are used worldwide as first-line agents for the treatment of neuropathic pain. Accumulating evidence indicates that one of the antihyperalgesic mechanisms of gabapentinoids is through activation of the noradrenergic pathway of the descending pain inhibition system. However, the involvement of the serotonin pathway is unclear. We investigated the effects of gabapentin (GBP) on the serotonergic pathway of the descending inhibitory system using the spinal nerve ligation (SNL) rat model. As in previous reports, administration of GBP to SNL rats improved paw withdrawal thresholds (PWT). Intrathecally administered serotonin receptor antagonists abolished GBP's amelioration in PWT. GBP did not ameliorate PWT in noradrenaline-depleted SNL rats by DSP-4. However, GBP ameliorated PWT in serotonin-depleted SNL rats by para-chlorophenylalanine, which was not inhibited by intrathecal administration of a serotonin receptor antagonist. Immunohistochemical analysis of serotonin in the spinal dorsal horn revealed a slight, albeit statistically insignificant, increase in 5-HT levels in SNL rats compared to naive rats. However, no apparent changes were observed before or after GBP administration in naive and SNL rats. In conclusion, the involvement of the serotonergic pathway in the antihyperalgesic effects of GBP on the spinal cord is secondary, although it cooperates with the noradrenergic system to produce analgesia.

The aim of the study was to analyze the literature sources for pharmacodynamic and pharmacokinetic features of gabapentin, providing its use in patients with neuropathic pain, as well as a comparative evaluation of its efficacy and safety when used in different doses.Materials and methods. PubMed, Google Scholar, EMBASE, ResearchGate scientific information network and elibrary.ru databases were used as search resources. The keywords used for the search were “gabapentin”, “mechanism of action”, “gabapentin targets”, “gabapentin pharmacodynamics”, “pharmacokinetics”, “pharmacokinetic parameters”, “neuropathic pain”, and “randomized clinical trials”. The depth of the search was 26 years (from 1998 to 2024). This review resulted in 87 literature sources.Results. Neuropathic pain (NeP) is one of the most common types of chronic pain, characterized by a high prevalence among people of the working age. Effective pharmacotherapy aimed at eliminating the pain syndrome is a key tool for improving the quality of life and preserving the work capacity of patients. Heterogeneity of etiologic factors involved in the genesis of NeP indicates the need to use drugs the analgesic effect of which is based on weakening the transmission of pain impulses in the CNS. In clinical trials, gabapentin has demonstrated efficacy in reducing the severity of pain in patients with postherpetic NeP, painful diabetic neuropathy and many other conditions accompanied by NeP. The dose of gabapentin 300 mg/day is the initial dose in the therapy of NeP and requires a further slow titration depending on the patient’s response to therapy and tolerability of the drug, especially in elderly and senile patients, as well as in patients with an impaired renal function. According to the published data, the most pronounced analgesic effect is achieved in the patients against the background of the gabapentin administration at a dose of 3600 mg/day.Conclusion. Gabapentin is the drug of choice in the management of patients with NeP of different etiology and intensity. A satisfactory safety profile and pharmacodynamic effects make gabapentin possible, despite the long history of its use, to remain a relevant drug used by a wide range of physicians, specialties, for pharmacotherapy of NeP patients.

Background and Aims: Gabapentin (GBP) has been found to decrease the pain scores and analgesic requirements following total abdominal hysterectomy, spinal surgery, and ear, nose, and throat surgery. It has been suggested that central neuronal sensitization may play an important role in postoperative pain. This study compares the effect of two different doses of preemptive GBP on morphine requirement and postoperative pain relief in patients undergoing mastectomy. Methods: This randomized comparative trial included 70 patients scheduled for unilateral mastectomy. They were divided into two groups. Group 1 received 800 mg oral GBP and Group 2 received 1200 mg oral GBP 2 h before surgery. After surgery, we recorded the pain score at different time points using the Visual Analog Scale (VAS) at rest. Patients were also asked about possible side effects of the premedication drug. Patients received morphine 0.1 mg/kg intravenous on demand. The time of first rescue analgesia was recorded along with the total rescue analgesic requirement in the first 24 h. Results: In our study, the mean VAS score, postoperatively at 2, 4, 12, 24 h in Group 2, was less than Group 1 but the difference was not statistically significant (P = 0.9, 0.1, 0.8, 0.4, respectively) Patients of Group 1 demanded rescue analgesia earlier (5.8 ± 3.4 h) than Group 2 (9.6 ± 5.9 h). The total 24 h morphine consumption in Group 1 (10.97 ± 4.01 mg) was higher than Group 2 (6.71 ± 5.02 mg). No significant side effects were observed during the perioperative period. Conclusion: We conclude that GBP in higher doses, when used preemptively, provides a greater degree of analgesia with opioid-sparing effect.

Background: Effective attenuation of the sympathetic surge due to laryngoscopy and endotracheal intubation is needed. We wanted to compare the role of oral gabapentin (600 mg) and oral pregabalin (150 mg) in controlling this sympathetic surge. Aims and Objectives: To compare the role of oral gabapentin (600 mg) and oral pregabalin (150 mg) as premedications for attenuating hemodynamic surge to laryngoscopy and endotracheal intubation. Materials and Methods: 90 patients aged 18–45 years with ASA grade I or II posted for elective surgical procedure under general anesthesia were randomly allocated to two equal groups (45 in each group) to receive either 600 mg oral gabapentin or 150 mg oral pregabalin 1 h prior to surgery. Heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and rate pressure product (RPP) were recorded after intubation at 1 (T1), 3 (T3), 5 (T5), and 10 (T10) min. Post-operative sedation and post-operative nausea and vomiting (PONV) were recorded and compared. Results: Gabapentin attenuates hemodynamic surge in terms of HR, SBP, DBP, MAP, and RPP better than pregabalin during laryngoscopy and endotracheal intubation at 3, 5, and 10 min after intubation, while there was no significant difference between the two groups at 1 min after intubation. Post-operative sedation score and adverse effects like PONV and SpO2 fluctuations at different points in time were comparable. Conclusion: Oral gabapentin (600 mg) was found to be more effective than oral pregabalin (150 mg) in attenuating the hemodynamic surge to laryngoscopy and intubation.

Background: Gabapentin is increasingly recognised for its potential for abuse, raising concerns within healthcare communities. Community pharmacists are on the front lines in identifying and addressing instances of gabapentin abuse, making their insights invaluable. This study aims to assess community pharmacists’ experiences and perceptions regarding gabapentin abuse in Jordan.Methods: A cross-sectional study was conducted from April to June 2024 using a questionnaire-based approach. The questionnaire, developed in English, was uploaded to Google Forms and distributed through social networking platforms. It consisted of four sections: demographic information, pharmacists’ experiences with gabapentin abusers, strategies to limit access to gabapentin, and perceptions of gabapentin abuse, which were assessed using a 5-point Likert scale. A Chi-square test was employed to analyze the association between categorical variables.Results: The study included 209 pharmacists (median age 29.0 years, IQR 8.0 years). Concerning gabapentin, 72.7% of pharmacists received requests to sell it in the past 6 months. Of these, about 75.7% encountered suspected gabapentin abusers, noting behavioural changes (95.9%), frequent refill requests (90.4%), and inconsistent medical histories (87.8%) as key indicators. Most suspected abusers were male (81.7%) and aged 21–30 years (74.8%).Common reasons cited by suspected abusers for requesting gabapentin included neuropathic pain (93.0%), low back pain (89.6%), and mood instability (73.0%). Pharmacists perceived an increase in gabapentin abuse (74.5%) and expressed a need for additional training (83.3%). Additionally, 83.7% recognised their pivotal role in identifying and addressing gabapentin abuse. Finally, significant associations were found between working in chain pharmacies and receiving gabapentin requests (χ² = 9.159, p = 0.002).Conclusion: Pharmacists have an important role in detecting gabapentin abuse which necessitates adequate education. Pharmacists have concerns regarding this issue and believe stricter regulations are needed.

AbstractComplex regional pain syndrome (CRPS) is a debilitating chronic pain condition that, although exceedingly rare, carries a significant burden for the affected patient population. The complex and ambiguous pathophysiology of this condition further complicates clinical management and therapeutic interventions. Furthermore, being a diagnosis of exclusion requires a diligent workup to ensure an accurate diagnosis and subsequent targeted management. The development of the Budapest diagnostic criteria helped to consolidate existing definitions of CRPS but extensive work remains in identifying the underlying pathways. Currently, two distinct types are identified by the presence (CRPS type 1) or absence (CRPS type 2) of neuronal injury. Current management directed at this disease is broad and growing, ranging from non-invasive modalities such as physical and psychological therapy to more invasive techniques such as dorsal root ganglion stimulation and potentially amputation. Ideal therapeutic interventions are multimodal in nature to address the likely multifactorial pathological development of CRPS. Regardless, a significant need remains for continued studies to elucidate the pathways involved in developing CRPS as well as more robust clinical trials for various treatment modalities.

OBJECTIVE: The aim of this retrospective study was to evaluate the effectiveness and safety of topical gabapentin solution (250 mg/mL) for the management of burning mouth syndrome (BMS). STUDY DESIGN: A retrospective chart review was conducted of all patients diagnosed with BMS and managed with gabapentin 250 mg/mL solution (swish and spit) between January 2021 and October 2022. Patient-reported outcomes included changes in burning score ranked on a 10-point numeric rating scale (NRS) and reported adverse drug reactions (ADR). Wilcoxon signed-rank test was used to assess differences in the oral burning score ranked on a NRS (0-10) between the baseline visit and the second visit. RESULTS: A total of 19 patients (68.4% females) with BMS were included and evaluated for follow-up at a median of 86 days (range: 29-195). Overall, patients reported a median 2-point burning decrease on a 0-10 NRS between the baseline visit and the second visit (p < 0.01). ADRs were reported by 3 patients (15.8%). CONCLUSION: Although this was a small retrospective study, BMS management with topical gabapentin (250 mg/mL) appears to be effective and well-tolerated. Future randomized prospective studies are needed to verify these preliminary findings.

BACKGROUND: There are several well-known treatments for Restless Legs Syndrome (RLS), including dopamine agonists (pramipexole, ropinirole, rotigotine), anticonvulsants (gabapentin and its analogs, pregabalin), oral or intravenous iron, opioids and benzodiazepines. However, in clinical practice, treatment is sometimes limited due to incomplete response or side effects and it is necessary to be aware of other treatment options for RLS, which is the purpose of this review. METHODS: We performed a narrative review detailing all of the lesser known pharmacological treatment literature on RLS. The review purposefully excludes well-established, well-known treatments for RLS which are widely accepted as treatments for RLS in evidence-based reviews. We also have emphasized the pathogenetic implications for RLS of the successful use of these lesser known agents. RESULTS: Alternative pharmacological agents include clonidine which reduces adrenergic transmission, adenosinergic agents such as dipyridamole, glutamate AMPA receptor blocking agents such as perampanel, glutamate NMDA receptor blocking agents such as amantadine and ketamine, various anticonvulsants (carbamazepine/oxcarbazepine, lamotrigine, topiramate, valproic acid, levetiracetam), anti-inflammatory agents such as steroids, as well as cannabis. Bupropion is also a good choice for the treatment of co-existent depression in RLS because of its pro-dopaminergic properties. DISCUSSION: Clinicians should first follow evidence-based review recommendations for the treatment of RLS but when the clinical response is either incomplete or side effects are intolerable other options can be considered. We neither recommend nor discourage the use of these options, but leave it up to the clinician to make their own choices based upon the benefit and side effect profiles of each medication.

BackgroundGabapentin has been adopted in Enhanced Recovery After Surgery protocols as a means to reduce opioid consumption while maintaining adequate post-operative analgesia. The purpose of our study was to review and compare changes in length of stay, opioid use, and patient reported pain scores after the addition of gabapentin into five, distinct pain protocols for posterior spinal fusion in adolescent idiopathic scoliosis.MethodsA retrospective review was completed using a database of electronic medical data from a single pediatric orthopedic healthcare system that was queried for patients with adolescent idiopathic scoliosis who underwent first-time posterior spinal fusion. Perioperative data including demographics, hospital length of stay, surgical details, opioid use, patient reported pain scores, and non-opioid analgesic use were collected.ResultsFrom December 2012 to February 2019, 682 hospitalizations for posterior spinal fusion in adolescent idiopathic scoliosis were identified with complete inpatient data; 49% were administered gabapentin. For the gabapentin cohort, the system saw no statistically significant effect on length of stay or pain averaged over POD#0-3. Opioid use was statistically lower averaged over POD#0-3. Individual sites saw variation on length of stay and opioid use compared to the system.ConclusionIn conclusion, system-wide data showed gabapentin containing protocols reduced opioid use while maintaining clinically equivalent analgesia. However, variations of individual site results make it difficult to conclude the degree to which gabapentin were responsible for this effect.

ObjectivesThe objective of this review is to provide updated information on the epidemiology, correlating factors and treatment of chronic kidney disease associated restless legs syndrome (CKD-A-RLS) in both adult and pediatric population.Materials and methodsWe have reviewed the Medline search and Google Scholar search up to May 2022, using key words restless legs syndrome, chronic kidney disease and hemodialysis and kidney transplant. The reviewed articles were studied for epidemiology, correlating factors, as well as pharmacologic and non-pharmacologic treatment options.ResultsOur search revealed 175 articles, 111 were clinical trials or cross- sectional studies and 64 were review articles. All 111 articles were retrieved and studied in detail. Of these, 105 focused on adults and 6 on children. A majority of studies on dialysis patients reported a prevalence between 15-30%, which is notably higher than prevalence of RLS in general population (5-10%). The correlation between presence of CKD-A-RLS with age, gender, abnormalities of hemogram, iron, ferritin, serum lipids, electrolytes and parathyroid hormones were also reviewed. The results were inconsistent and controversial. Limited studies have reported on the treatment of CKD-A-RLS. Non-pharmacological treatment focused on the effect(s) of exercise, acupuncture, massage with different oils and infra-red light whereas, pharmacologic treatment options include the effects of dopaminergic drugs, Alpha2-Delta ligands (gabapentin and pregabalin), vitamins E and C, and intravenous iron infusion.ConclusionThis updated review showed that RLS is two to three times more common in patients with CKD compared to the general population. More patients with CKD-A-RLS demonstrated increased mortality, increased incidence of cardiovascular accident, depression, insomnia and impaired quality of life than those with CKD without RLS. Dopaminergic drugs such as levodopa, ropinirole, pramipexole and rotigotine as well as calcium channel blockers (gabapentin and pregabalin) are helpful for treatment of RLS. High quality studies with these agents are currently underway and hopefully confirm the efficacy and practicality of using these drugs in CKD-A-RLS. Some studies have shown that aerobic exercise and massage with lavender oil can improve symptoms of CKD-A- RLS suggesting that these measures can be useful as adjunct therapy.

ObjectivesThe purpose of this study was to assess serum concentrations of gabapentin in cats with chronic kidney disease (CKD) vs clinically healthy cats.MethodsFive healthy cats were enrolled in a pharmacokinetic study. A single 20 mg/kg dose of gabapentin was administered orally and blood was obtained at 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 8, 12, 24 and 36 h via a jugular catheter. Serum gabapentin concentrations were measured using liquid chromatography coupled to tandem mass spectrometry. Non-compartmental pharmacokinetic analysis was performed. The same five healthy cats plus 25 cats with stable International Renal Interest Society stage 2 (n = 14) and 3 (n = 11) CKD were enrolled in a limited sampling study. Cats in both groups received a single 10 mg/kg dose of gabapentin, and serum gabapentin concentrations and compliance scores were obtained 3 and 8 h post-administration.ResultsCats with CKD had significantly higher dose-normalized serum gabapentin concentrations than normal cats at 3 h (P = 0.0012 CKD vs normal 10 mg/kg; P = 0.008 CKD vs normal 20 mg/kg) and 8 h (P

BACKGROUND: Surgeons have made substantial efforts to decrease postoperative opioid prescribing, largely because it can lead to prolonged use. These efforts include adoption of non-opioid pain medication including gabapentin. Like opioids, gabapentin use may be prolonged, increasing the risk of altered mental status and even overdose and death when taken concurrently with opioids. However, little is known about postoperative prolonged use of gabapentin in older adults. METHODS: We merged a 20% sample of Medicare Carrier, MedPAR and Outpatient Files with Part D for 2013-2018. We included patients >65 years old without prior gabapentinoid use who underwent common non-cataract surgical procedures. We defined new postoperative gabapentin as fills for 7 days before surgery until 7 days after discharge. We excluded patients whose discharge disposition was hospice or death. The primary outcome was prolonged use of gabapentin, defined as a fill>90 days after discharge. To identify risk factors for prolonged use, we constructed logistic regression models, adjusted for procedure and patient characteristics, length of stay, disposition location, and care complexity. RESULTS: Overall, 17,970 patients (3% of all eligible patients) had a new prescription for gabapentin after surgery. Of these, the mean age was 73 years old and 62% were female. The most common procedures were total knee (45%) and total hip (21%) replacements. Prolonged use occurred in 22%. Those with prolonged use were more likely to be women (64% vs. 61%), be non-White (14% vs. 12%), have concurrent prolonged opioid use (44% vs. 18%), and have undergone emergency surgery (8% vs. 4%). On multivariable analysis, being female, having a higher Charlson comorbidity score, having an opioid prescription at discharge and at >90 days and having a higher care complexity were associated with prolonged use of gabapentin. CONCLUSIONS: More than one-fifth of older adults prescribed gabapentin postoperatively filled a prescription >90 days after discharge, especially among patients with more comorbidities and concurrent prolonged opioid use, increasing the risk of adverse drug events and polypharmacy.

AbstractFalls pose a significant threat to older adults, resulting in injuries and mortality. Concurrently prescribed opioids and gabapentin for pain management may increase fall risks in older patients. This study aimed to estimate fall risks associated with the concurrent use of gabapentin and opioids, comparing them to opioid monotherapy in older adults. A retrospective case-control study of 1,813 patients aged 65–89 on chronic opioid therapy (2017–2020), excluding those with a fall history, analysis focused on the first fall occurrence. Logistic regression assessed the association between concurrent gabapentin and opioid use and fall events. Out of eligible patients, 122 (6.73%) experienced falls during opioid therapy, with 232 (12.80%) having concurrent gabapentin use. Concurrent use significantly increased fall risk (AOR = 1.73; 95% CI: 1.08-2.78). Being female, aged ≥81, and having more chronic conditions also increased risk. Mitigating fall risk in older adults requires education on prevention, exploring alternative pain management, and careful consideration of prescribing. Further research is crucial to understand adverse events linked to combined opioid and gabapentin use in the geriatric population. [ABSTRACT FROM AUTHOR]

Simple Summary: Gabapentin is a medication often prescribed to dogs for some types of pain and/or behavioral disorders. This study surveyed dog owners regarding the effectiveness and side effects of gabapentin when it was prescribed for their dogs with problem behaviors. According to the owners in this study, gabapentin was well-tolerated with minimal side effects in most dogs. Few reported side effects were considered bothersome, and none were a cause for discontinuation of the medication. The most common reason owners gave for discontinuation of gabapentin was perceived lack of effectiveness. Sedation was the most commonly reported side effect, mostly when given at high doses. Close to one-third of owners reported that their dogs displayed no unwanted side effects, even at the highest doses. Overall, gabapentin appears to be a safe and well-tolerated medication choice for dogs with behavior disorders. Specific dose ranges (milligram per kilogram of body weight) did not correlate with reports of side effects nor effectiveness, suggesting that some dogs may be more sensitive or resistant to adverse and/or therapeutic effects than others and multiple dosage trials may be needed before finding the best fit. The use of gabapentin in treating dogs with behavioral disorders is not well described. To characterize behavioral effects of gabapentin, this study surveyed 50 owners whose dogs were prescribed gabapentin at a veterinary behavior-focused practice over a five-year period. Most owners (72%) reported that gabapentin was moderately or very effective at improving their dog's behavior. The majority of owners reported at least one side effect (70%), with sedation being the most common. Sedation was more likely to be seen at doses higher than 30 mg/kg. Specific dose ranges (mg/kg) did not correlate with any other reports of side effects nor effectiveness. Dogs with a diagnosis of conflict-related aggression were more likely to have owners report that gabapentin was effective at improving behavior compared to dogs with other behavioral diagnoses (p = 0.04), while dogs diagnosed with aggression secondary to high arousal were less likely to have owners report that gabapentin was effective (p = 0.01). Overall, reports of effect varied widely and, with the exception of sedation, did not correlate with specific mg/kg dose ranges. Results suggest that some dogs may be more sensitive or resistant to adverse and/or therapeutic effects than others and multiple dosage trials may be needed before finding the best fit. [ABSTRACT FROM AUTHOR]

Objective. To compare the effects of oral gabapentin (GBP) and pregabalin (PGB) in pain control after orthopedic surgery on the upper limb. Methods. In this double-blind randomized clinical trial study, 80 patients who were the candidates for elective orthopedic surgery on one of the parts of the upper limb were divided into two groups using balance-block randomization. For the first group, a 150 mg capsule of PGB (one hour before the surgery) and for the second group, a 300 mg capsule of GBP (two hours before the surgery) were prescribed. Patients were subjected to standard monitoring at the beginning and during surgery. The pain scores were evaluated at before surgery, in PACU (postanesthesia care unit), and 6 and 12 hours after the surgery by VAS (visual analog scale). Results. In this study, 37 subjects were allocated to each group. The participation rate was 92.5%. The mean with 95% confidence interval (CI) of pain scores over 4 times in the PGB group was 4.03 (3.25–4.79), 3.76 (3.02–4.49), 3.65 (3.06–4.23), and 3.41 (2.88–3.93) and in the GBP group was 4.08 (3.33–4.83), 2.78 (2.11–4.45), 2.3 (2.05–2.54), and 2 (1.51–2.50), respectively. The within-group comparisons showed a significant decrease in the pain score over time (P < 0.001). Also, the between-group comparison showed significant differences between the two groups in terms of pain score (P < 0.001). In the end, results showed that there is a significant interaction between time and intervention for pain score (P = 0.042). Conclusion. Although two medicines led to a reduction in the pain score, but the rate reduction in the PGB group was significantly more than that in the GBP group. This trial is registered with IRCT20211013052759N1. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to compare the efficacy and safety of baclofen and gabapentin in reducing leg pain from nocturnal calf cramps in lumbar spinal stenosis patients. Design: In a randomized clinical trial, the patients with lumbar spinal stenosis who commonly experienced nocturnal calf cramps were included. Patients were randomly assigned to either the baclofen or gabapentin group. Overall leg pain intensity, nocturnal calf cramp frequency and severity, sleep disturbances and functional disability were assessed at baseline and after 4 and 12 wks. Results: Thirty-six patients completed the 3-mo study. Both gabapentin and baclofen groups showed a significant reduction in overall leg pain, calf cramp frequency and intensity, and insomnia severity index scores frombaseline to the endpoint. However, therewere no significant differences between the two groups in terms of symptom reduction at different time points. The baclofen group also demonstrated a significant decrease in Oswestry Disability Index scores (P < 0.001), while the gabapentin group did not (P = 0.344). No adverse effects were reported in either group. Conclusions: Baclofen seems to be as effective and as safe as gabapentin in treating nocturnal calf cramps in lumbar spinal stenosis patients and even shows superiority in enhancing functional outcomes. [ABSTRACT FROM AUTHOR]

Gabapentinoids are used worldwide as first-line agents for the treatment of neuropathic pain. Accumulating evidence indicates that one of the antihyperalgesic mechanisms of gabapentinoids is through activation of the noradrenergic pathway of the descending pain inhibition system. However, the involvement of the serotonin pathway is unclear. We investigated the effects of gabapentin (GBP) on the serotonergic pathway of the descending inhibitory system using the spinal nerve ligation (SNL) rat model. As in previous reports, administration of GBP to SNL rats improved paw withdrawal thresholds (PWT). Intrathecally administered serotonin receptor antagonists abolished GBP's amelioration in PWT. GBP did not ameliorate PWT in noradrenaline-depleted SNL rats by DSP-4. However, GBP ameliorated PWT in serotonin-depleted SNL rats by para-chlorophenylalanine, which was not inhibited by intrathecal administration of a serotonin receptor antagonist. Immunohistochemical analysis of serotonin in the spinal dorsal horn revealed a slight, albeit statistically insignificant, increase in 5-HT levels in SNL rats compared to naive rats. However, no apparent changes were observed before or after GBP administration in naive and SNL rats. In conclusion, the involvement of the serotonergic pathway in the antihyperalgesic effects of GBP on the spinal cord is secondary, although it cooperates with the noradrenergic system to produce analgesia. • Serotonin receptor antagonists antagonized antihyperalgesic effects of gabapentin. • Gabapentin had no antihyperalgesic effect when noradrenaline was depleted. • Serotonin depletion did not alter the antihyperalgesic effect of gabapentin. • 5-HT showed a non-significant increase in SNL rats. • 5-HT in the spinal cord did not change before or after gabapentin administration. [ABSTRACT FROM AUTHOR]

Gabapentin (GBP) was originally developed as a potential agonist for Gamma-Amino-Butyric-Acid (GABA) receptors, aiming to inhibit the activation of pain-signaling neurons. Contrary to initial expectations, it does not bind to GABA receptors. Instead, it exhibits several distinct pharmacological activities, including: (1) binding to the alpha-2-delta protein subunit of voltage-gated calcium channels in the central nervous system, thereby blocking the excitatory influx of calcium; (2) reducing the expression and phosphorylation of CaMKII via modulation of ERK1/2 phosphorylation; (3) inhibiting glutamate release and interfering with the activation of NMDA receptors; (4) enhancing GABA synthesis; (5) increasing cell-surface expression of δGABA_A receptors, contributing to its antinociceptive, anticonvulsant, and anxiolytic-like effects. Additionally, GBP displays (6) inhibition of NF-kB activation and subsequent production of inflammatory cytokines, and (7) stimulation of the purinergic adenosine A1 receptor, which supports its anti-inflammatory and wound-healing properties. Initially approved for treating seizures and postherpetic neuralgia, GBP is now broadly used for various conditions, including psychiatric disorders, acute and chronic neuropathic pain, and sleep disturbances. Recently, as an eye drop formulation, it has also been explored as a therapeutic option for ocular surface discomfort in conditions such as dry eye, neurotrophic keratitis, corneal ulcers, and neuropathic ocular pain. This review aims to summarize the evidence supporting the molecular effects of GBP, with a special emphasis on its applications in ocular surface diseases. [ABSTRACT FROM AUTHOR]

The increasing use and misuse of gabapentin pose a major risk to public health and traffic safety. Gabapentin has been approved by the Food and Drug Administration (FDA) since 1993 for adjunctive therapy in the treatment of epilepsy and neuralgia but is increasingly being prescribed for numerous off-label uses including insomnia, anxiety, depression, and migraine. Reported side effects include blurred vision, drowsiness, and loss of coordination. Driving behaviors such as exiting the lane of travel and crashes have been reported in connection to drugged driving investigations concerning gabapentin. To further assist with the toxicological interpretation of gabapentin in driving under the influence of drugs (DUID) scenarios, a review of approximately 108,000 gabapentin-positive DUID cases was conducted. Of those, 858 cases met inclusion criteria and underwent additional evaluation. Blood specimens were screened via enzyme-linked immunosorbent assay (ELISA) and confirmed by liquid chromatography tandem mass spectrometry (LC-MS/MS) for quantitation of gabapentin. This review found an overall DUID gabapentin positivity of 7.9% between January 2020 and December 2022; 17 states from various geographical regions had at least one positive gabapentin DUID case. Observations in six driving and human performance cases where gabapentin was the only drug reported were consistent with the known adverse effects of the medication. Half of the case histories reviewed involved crashes where the driver was determined to be at fault. Additionally, 94% of the cases in this review involved gabapentin in combination with other drugs. The most prevalent drug combinations were opioids and gabapentin present in 64% of cases. [ABSTRACT FROM AUTHOR]