Efficacy and Clinical Value of Commonly Used Ingredients in Pain Management Compounds: A Literature Review.

The need for continued improvement in pain management is growing. This review is aimed towards identifying the literature regarding clinical and therapeutic value of the commonly used ingredients in pain management compounds: lidocaine, tetracaine, ketoprofen, ketamine, and gabapentin. Prospectively, future studies should be conducted to identify the exact benefits and side effects of compounded pain management therapies, such that these compounds can be effectively utilized when deemed appropriate.

Diabetic Peripheral Neuropathy: Prevention and Treatment.

Diabetic peripheral neuropathy occurs in up to 50% of patients with diabetes mellitus and increases the risk of diabetic foot ulcers and infections. Consistent screening and clear communication are essential to decrease disparities in assessment of neuropathic symptoms and diagnosis. Physicians should address underlying risk factors such as poor glycemic control, vitamin B12 deficiency, elevated blood pressure, and obesity to reduce the likelihood of developing neuropathy. First-line drug therapy for painful diabetic peripheral neuropathy includes duloxetine, gabapentin, amitriptyline, and pregabalin; however, these medications do not restore sensation to affected extremities. Evidence for long-term benefit and safety of first-line treatment options is lacking. Second-line drug therapy includes nortriptyline, imipramine, venlafaxine, carbamazepine, oxcarbazepine, topical lidocaine, and topical capsaicin. Periodic, objective monitoring of medication response is critical because patients may not obtain desired pain reduction, adverse effects are common, and serious adverse effects can occur. Opioids should generally be avoided. Nondrug therapies with low- to moderate-quality evidence include exercise and neuromodulation with spinal cord stimulation or transcutaneous electrical nerve stimulation. Peripheral transcutaneous electrical nerve stimulation is well tolerated and inexpensive, but benefits are modest. Other treatments, such as acupuncture, alpha-lipoic acid, acetyl-L-carnitine, cannabidiol, and onabotulinumtoxinA need further study in patients with diabetic peripheral neuropathy.

Pregabalina preoperatoria previene las fasciculaciones y mialgias inducidas por succinilcolina: metaanálisis de ensayos aleatorizados / Preoperative pregabalin prevents succinylcholine-induced fasciculations and myalgias: A meta-analysis of randomized trials

La succinilcolina es el bloqueador neuromuscular de referencia para la inducción de secuencia rápida. Sin embargo, su uso se asocia a fasciculaciones y mialgias. Se realizó una revisión sistemática y un metaanálisis. Se incluyeron ensayos clínicos controlados aleatorizados comparando gabapentinoides frente a placebo, para la prevención de fasciculaciones y mialgias inducidas por succinilcolina. Se incluyeron seis estudios clínicos aleatorizados. El número total de pacientes fue de 481, de los cuales 241 se incluyeron en el grupo de intervención y 240 en el grupo de placebo. Los gabapentinoides redujeron la incidencia de mialgia inducida por succinilcolina (RR=0,69; IC95%: 0,56-0,84; p<0,001), que siguió siendo estadísticamente significativa para pregabalina (RR=0,71; IC95%: 0,54-0,93; p=0,013) y gabapentina (RR=0,61; IC95%: 0,45-0,82; p=0,001) por separado. No hubo diferencia entre los grupos en cuanto a fasciculaciones (RR=0,92; IC95%: 0,82-1,03; p=0,148). El uso preoperatorio de gabapentinoides se asocia a una menor incidencia de mialgias inducidas por succinilcolina dentro de las primeras 24horas posteriores al procedimiento. (AU)

Succinylcholine is the gold standard neuromuscular blocker for rapid sequence induction, however, its use is associated with fasciculations and myalgias. A systematic review and meta-analysis including randomized controlled clinical trials was performed comparing gabapentinoids versus placebo for the prevention of fasciculations and succinylcholine-induced myalgias. Six randomized clinical studies were included. The total number of patients was 481, of which 241 were in the intervention group and 240 in the placebo group. Gabapentinoids reduced the incidence of succinylcholine-induced myalgia (RR=.69; 95%CI: .56-.84; P<.001), which remained statistically significant for pregabalin (RR=.71; 95%CI: .54-.93; P=.013) and gabapentin (RR=.61; 95%CI: .45-.82; P=.001) separately. There was no difference between the groups in fasciculations (RR=.92; 95%CI: .82-1.03; P=.148). Preoperative use of gabapentinoids is associated with lower incidence of succinylcholine-induced myalgias within the first 24hours after the procedure. (AU)

Analysis of drug-impregnated paper samples seized in English prisons between 2018 and 2020.

Novel psychoactive substances (NPS) in the form of impregnated papers delivered to prisoners are of particular concern in prison settings, where they are commonly used by vaping. The purpose of this study was to create a qualitative method for identifying the various emerging NPS impregnated onto paper samples sent to prisoners. It helps to demonstrate that these findings can be used to predict drug prevalence and trends in prisons. Between 2018 and 2020, 1250 non-judicial paper samples seized from 12 English prisons were analysed to determine the NPSs being circulated. Approximately 1 cm2 paper were cut and added to 50 % (v/v) methanol in LCMS-grade water. Vortex-mixing was used to prepare extracts (30 min). Q-TOF LC/MS was used to screen the extracts. This study showed that synthetic cannabinoid receptor agonist (SCRA) was the most common drug group detected in impregnated paper seizures in English prisons between 2018 and 2020, followed by cocaine, heroin type drugs (A) and amphetamine, ketamine type drugs (B). Male prisons had a higher prevalence of SCRAs, whereas female prisons had a higher prevalence of A drugs. Furthermore, lower security prisons were found to have a higher prevalence of B drugs, pregabalin, gabapentin type drugs (C), and abused and prescription drugs than higher security prisons which unveiled a higher prevalence of nicotine. The findings of this study have revealed new information about drug use in prisons. This study will also aid in the identification of drug smuggling routes into jails, keeping prison staff up to date with the trends.

Retigabine and gabapentin restore channel function and neuronal firing in a cellular model of an epilepsy-associated dominant-negative KCNQ5 variant.

KCNQ5 encodes the voltage-gated potassium channel KV7.5, a member of the KV7 channel family, which conducts the M-current. This current is a potent regulator of neuronal excitability by regulating membrane potential in the subthreshold range of action potentials and mediating the medium and slow afterhyperpolarization. Recently, we have identified five loss-of-function variants in KCNQ5 in patients with genetic generalized epilepsy. Using the most severe dominant-negative variant (R359C), we set out to investigate pharmacological therapeutic intervention by KV7 channel openers on channel function and neuronal firing. Retigabine and gabapentin increased R359C-derived M-current amplitudes in HEK cells expressing homomeric or heteromeric mutant KV7.5 channels. Retigabine was most effective in restoring K+ currents. Ten µM retigabine was sufficient to reach the level of WT currents without retigabine, whereas 100 µM of gabapentin showed less than half of this effect and application of 50 µM ZnCl2 only significantly increased M-current amplitude in heteromeric channels. Overexpression of KV7.5-WT potently inhibited neuronal firing by increasing the M-current, whereas R359C overexpression had the opposite effect and additionally decreased the medium afterhyperpolarization current. Both aforementioned drugs and Zn2+ reversed the effect of R359C expression by reducing firing to nearly normal levels at high current injections. Our study shows that a dominant-negative variant with a complete loss-of-function in KV7.5 leads to largely increased neuronal firing which may explain a neuronal hyperexcitability in patients. KV7 channel openers, such as retigabine or gabapentin, could be treatment options for patients currently displaying pharmacoresistant epilepsy and carrying loss-of-function variants in KCNQ5.

A comprehensive update on the ADMET considerations for α2δ calcium channel ligand medications for treating restless legs syndrome.

INTRODUCTION: Restless legs syndrome/Willis-Ekbom disease (RLS/WED) is a sleep-related sensory-motor disorder associated with poor sleep quality and impaired daily functioning. In patients affected by chronic RLS/WED, a pharmacological therapy is recommended. International guidelines suggest to start the treatment with a α2δ calcium channel ligand in most cases, unless contraindicated. AREAS COVERED: The present review is based on an extensive Internet and PubMed search from 1986 to 2024. Our purpose is to describe the absorption, distribution, metabolism, and toxicology (ADMET) of the α2δ ligands, with common consideration for the therapeutic class, specificities of different compounds, efficacy, and safety in relation to other treatment options. EXPERT OPINION: α2δ ligands are quite similar in their ADMET profiles, sharing most of the pharmacokinetics and potential adverse effects. However, we highlight the linear kinetic of gabapentin enacarbil and pregabalin, differently from gabapentin. α2δ ligands are safe and effective for the treatment of RLS/WED. Additional benefits can be obtained in comorbid insomnia, chronic pain syndromes, history of impulse control disorder, and comorbid anxiety. The use of α2δ ligands is associated with poor risk of augmentation. We still need new long-term safe and effective treatments, which could be developed along with our knowledge of RLS/WED pathophysiology.

SUNCT, SUNA and short-lasting unilateral neuralgiform headache attacks: Debates and an update.

BACKGROUND: Short-lasting unilateral neuralgiform headache attacks (SUNHA) have the features of both short-lasting unilateral neuralgiform pain, such as trigeminal neuralgia or stabbing headache, and associated trigeminal autonomic symptoms, such as paroxysmal hemicrania or cluster headache. Recognizing and adequately treating SUNHA is essential but current treatment methods are ineffective in treating SUNHA. METHODS: We reviewed the changes in the concept of short-lasting unilateral neuralgiform headache attacks and provide a narrative review of the current medical and surgical treatment options, from the first choice of treatment for patients to treatments for selective intractable cases. RESULTS: Unlike the initial impression of an intractable primary headache disorder affecting older men, SUNHA affects both sexes throughout their lifespan. One striking feature of SUNHA is that the attacks are triggered by cutaneous or intraoral stimulation. The efficacy of conventional treatments is disappointing and challenging, and preventive therapy is the mainstay of treatment because of highly frequent attacks of a very brief duration. Amongst them, lamotrigine is effective in approximately two-third of the patients with SUNHA, and intravenous lidocaine is essential for the management of acute exacerbation of intractable pain. Topiramate, oxcarbazepine and gabapentin are considered good secondary options for SUNHA, and botulinum toxin can be used in selective cases. Neurovascular compression is commonly observed in SUNHA, and surgical approaches, such as neurovascular compression, have been reported to be effective for intractable cases. CONCLUSIONS: Recent advances in the understanding of SUNHA have improved the recognition and treatment approaches for this unique condition.

A systematic review and critical appraisal of menopause guidelines.

OBJECTIVE AND RATIONALE: To identify and appraise current national and international clinical menopause guidance documents, and to extract and compare the recommendations of the most robust examples. DESIGN: Systematic review. DATA SOURCES: Ovid MEDLINE, EMBASE, PsycINFO and Web of Science ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Practice guidance documents for menopause published from 2015 until 20 July 2023. Quality was assessed by the Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument. RESULTS: Twenty-six guidance papers were identified. Of these, five clinical practice guidelines (CPGs) and one non-hormonal therapy position statement met AGREE II criteria of being at least of moderate quality. The five CPGs listed symptoms associated with the perimenopause and menopause to be vasomotor symptoms (VMS), disturbed sleep, musculoskeletal pain, decreased sexual function or desire, and mood disturbance (low mood, mood changes or depressive symptoms). Acknowledged potential long-term menopause consequences were urogenital atrophy, and increased risks of cardiovascular disease and osteoporosis. VMS and menopause-associated mood disturbance were the only consistent indications for systemic menopausal hormone therapy (MHT). Some CPGs supported MHT to prevent or treat osteoporosis, but specific guidance was lacking. None recommended MHT for cognitive symptoms or prevention of other chronic disease. Perimenopause-specific recommendations were scant. A neurokinin 3B antagonist, selective serotonin/norepinephrine (noradrenaline) reuptake inhibitors and gabapentin were recommended non-hormonal medications for VMS, and cognitive behavioural therapy and hypnosis were consistently considered as being of potential benefit. DISCUSSION: The highest quality CPGs consistently recommended MHT for VMS and menopause-associated mood disturbance, whereas clinical depression or cognitive symptoms, and cardiometabolic disease and dementia prevention were not treatment indications. Further research is needed to inform clinical recommendations for symptomatic perimenopausal women.

Optimizing twin-screw melt granulation: The role of overflight clearance on granulation behavior.

Twin-screw melt granulation (TSMG) relies on the dispersive and distributive mixing at the kneading zone for granule growth to happen highlighting the critical role played by the kneading elements in TSMG. Despite extensive research conducted on the impact of screw geometry in melt compounding, there is not enough literature for TSMG. Disc width for the kneading elements was 2 mm, contrary to the standard 5 mm. The objective of this study was to evaluate if varying overflight clearance (OC) can alter the paradigm for TSMG. The new elements reduce the peak shear at kneading zone however a higher barrel temperature and degree of fill (DoF) is required to compensate to attain similar granule attributes. The change in DoF was achieved through a combination of modified screw configuration to pre-densify powders before kneading and processing at a lower screw speed. Despite the higher barrel temperature, process optimization of thermally unstable gabapentin was carried out. Using the new elements, compressible granules (Tensile strength > 2 MPa) with low % GABA-L content were manufactured despite increasing OC to 0.4 mm. Granule stability at 40 °C, ambient humidity for 6 months indicated gabapentin was stable (% GABA-L ≪0.4 %) despite a high barrel temperature of 120 °C.

Gabapentin for Postoperative Pain Control and Opioid Reduction in Scrotal Surgery: A Randomized Controlled Clinical Trial.

PURPOSE: To assess the safety and efficacy of gabapentin in reducing postoperative pain among patients undergoing scrotal surgery for male infertility by conducting a randomized, double-blind, placebo-controlled trial. MATERIALS AND METHODS: In this randomized, double-blind, placebo-controlled trial, healthy men undergoing scrotal surgery with a single surgeon were randomized to receive either (1) gabapentin 600 mg given 2 hours preoperatively and 300 mg taken 3 times a day postoperatively for 3 days, or (2) inactive placebo. The primary outcome measure was difference in postoperative pain scores. Secondary outcomes included differences in opioid usage, patient satisfaction, and adverse events. RESULTS: Of 97 patients screened, 74 enrolled and underwent randomization. Of these, 4 men were lost to follow-up, and 70 were included in the final analysis (35 gabapentin, 35 placebo). Both differences in initial postoperative mean pain score (-1.14, 95% CI -2.21 to -0.08, P = .035) and final mean pain score differences (-1.27, 95% CI -2.23 to -0.32, P = .0097) indicated lower gabapentin pain compared to placebo. There were no statistically significant differences in opioid usage, patient satisfaction, or adverse events. CONCLUSIONS: These data suggest that perioperative gabapentin results in a statistically and clinically significant decrease in pain following scrotal surgery. While there was no evidence of an impact on opioid usage or patient satisfaction, given the low risk of adverse events, it may be considered as part of a multimodal pain management strategy.

Gabapentin in drugged driving investigations.

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.

Gabapentin attenuates cardiac remodeling after myocardial infarction by inhibiting M1 macrophage polarization through the peroxisome proliferator-activated receptor-γ pathway.

OBJECTIVES: 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]-1ß). 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-ß. 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-1ß). In vitro, gabapentin reduced NGF, iNOS, TNF-α, and IL-1ß 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. CONCLUSION: Gabapentin attenuates cardiac remodeling by inhibiting inflammation via peroxisome proliferator-activated receptor-γ activation and preventing calcium overload.

Pilot RCT comparing low-dose naltrexone, gabapentin and placebo to reduce pain among people with HIV with alcohol problems.

BACKGROUND: To estimate the effects on pain of two medications (low-dose naltrexone and gabapentin) compared to placebo among people with HIV (PWH) with heavy alcohol use and chronic pain. METHODS: We conducted a pilot, randomized, double-blinded, 3-arm study of PWH with chronic pain and past-year heavy alcohol use in 2021. Participants were recruited in St. Petersburg, Russia, and randomized to receive daily low-dose naltrexone (4.5mg), gabapentin (up to 1800mg), or placebo. The two primary outcomes were change in self-reported pain severity and pain interference measured with the Brief Pain Inventory from baseline to 8 weeks. RESULTS: Participants (N = 45, 15 in each arm) had the following baseline characteristics: 64% male; age 41 years (SD±7); mean 2 (SD±4) heavy drinking days in the past month and mean pain severity and interference were 3.2 (SD±1) and 3.0 (SD±2), respectively. Pain severity decreased for all three arms. Mean differences in change in pain severity for gabapentin vs. placebo, and naltrexone vs. placebo were -0.27 (95% confidence interval [CI] -1.76, 1.23; p = 0.73) and 0.88 (95% CI -0.7, 2.46; p = 0.55), respectively. Pain interference decreased for all three arms. Mean differences in change in pain interference for gabapentin vs. placebo, and naltrexone vs. placebo was 0.16 (95% CI -1.38, 1.71; p = 0.83) and 0.40 (95% CI -1.18, 1.99; p = 0.83), respectively. CONCLUSION: Neither gabapentin nor low-dose naltrexone appeared to improve pain more than placebo among PWH with chronic pain and past-year heavy alcohol use. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT4052139).

Challenging Case: A Multidisciplinary Approach to Demystifying Chronic Sleep Impairment in an Infant with a Complex Medical and Behavioral Profile.

CASE: X is a 22-month-old White male infant with a complex medical history, including diagnoses of FBXO11 mutation, hypotonia, restrictive lung disease and mild intermittent asthma, laryngotracheomalacia, obstructive sleep apnea (OSA), feeding difficulties with a history of aspiration, gastroesophageal reflux disease (GERD), and developmental delays. X's medical presentation has resulted in multiple prior medical admissions for respiratory failure due to acute illnesses, procedures and treatments including gastrojejunostomy (GJ) tube dependence, supraglottoplasty to reshape tissues of the upper larynx, and the use of biphasic positive airway pressure (BiPAP) at night and room air during the day when he is at baseline. In addition, he has nocturnal events characterized by significant agitation, screaming, crying, body stiffening and limb movements with pauses in breathing, mouth breathing, restless sleep, and difficulty waking in the morning with concomitant daytime fatigue despite above treatments for OSA. There is no history of congenital heart disease or sudden unexplained death. Family history is noncontributory because parents are negative for the FBXO11 variant.X's sleep disruption has led to significant sleep deficits for both X and his caregivers, who spend much of the night strategizing on how to console him. X has undergone several sleep studies, starting when X was aged 4 months, at several children's hospitals across the nation to determine the cause of his chronic sleep disturbance, which yielded limited information and treatment success. As an infant, X received a medical workup and was subsequently treated with a proton pump inhibitor (PPI) for reflux. At 12 months, he was diagnosed with disordered sleep with myoclonic jerks and started on melatonin and gabapentin for involuntary movements. At 13 months, gabapentin was weaned back because of intolerance, and at 15 months, nortriptyline and clonidine were started because of worsening symptoms to target potential neuropathic pain. While most of his symptoms were at night, he had occasional daytime screaming episodes, particularly when experiencing illness. Gabapentin and clonidine were stopped because nortriptyline seemed most effective.At 17 months, the results from a sleep study led to a diagnosis of night terrors, and several clinicians agreed that X's sleep disruption was behavioral in nature. At this time, an infant mental health consultant met with a sleep psychologist on the family's behalf to support family in considering systematic desensitization therapy to increase tolerance to wearing his BiPAP mask, as well as other behavioral and sleep hygiene strategies, which were tried on several occasions and again, resulted in limited improvement in functioning.At 19 months, X's multidisciplinary team reconsidered a night terror diagnosis after a failed trial of clonazepam and pursued a differential diagnosis of periodic limb movement disorder (PLMD). X trialed gabapentin again, but this time only a nighttime dose, per sleep medicine and psychiatry recommendation. While this brought some temporary relief from nighttime distress, despite increasing to the highest dose for age and weight (15 mg/kg/dose), this became less effective, and he was weaned off at 22 months. He had been on iron supplementation since age 6 months and received an iron infusion at 22 months because of persistently low ferritin levels and PLMD in sleep.At 24 months, X was briefly trialed on levetiracetam. While no evidence for seizures on EEG was present, this medication was chosen for involuntary movements and genetic risk for seizures. However, this medication was not useful. At 25 months, an evaluation with a movement disorder physiatrist resulted in a diagnosis of nocturnal paroxysmal dystonia, and he was started on baclofen, which has provided some, but not complete relief to nighttime symptoms. Parents are reporting he has more "good nights" than "bad nights," but "bad nights" come in stretches of a few days in length with no known trigger or relief.Most recently, X was evaluated by general genetics. Whole exome sequencing (WES) was pursued which revealed a pathogenic de novo variant in FBXO11 and provides a likely cause for his neurodevelopmental phenotype. However, he has some features not explained by FBX011; thus, reanalysis of his WES was performed and revealed a de novo variant of uncertain significance in RAF1. Because pathogenic variants in RAF1 have been associated with dilated cardiomyopathy and Noonan spectrum disorder, it was recommended that X be followed periodically in a cardiac genetics clinic. Family is well connected into the FBXO11 community, including supportive Facebook groups. Parents have shared that they do not feel X's breathing issues and pain fit with the phenotype of other children with FBXO11 mutations.X is also enrolled in a medical child care program to facilitate development and social-emotional functioning and receives learning, speech, occupational, physical, and feeding therapy while in attendance. Despite periods of absence due to contracting numerous viral illnesses over the past several months, X continues to make progress across developmental therapies and happily engages when at the program.What additional diagnostic tests and treatment should be considered to better understand X's medical and behavioral presentation? What are the implications of chronic sleep deprivation and stress on the behavior and development of infant with X's profile? What are important psychosocial considerations because it relates to children with medical complexity (CMC), particularly for X and his family to support caregiver, family, and X's quality of life and overall well-being?

Efficacy of topical gabapentin in women with primary macular amyloidosis: A side-by-side triple-blinded randomized clinical trial.

BACKGROUND: Primary cutaneous macular amyloidosis (PCMA) is a chronic pruritic cutaneous disease characterized by heterogeneous extracellular deposition of amyloid protein in the skin. AIMS: This study aimed to evaluate the efficacy of topical 6% gabapentin cream for the treatment of patients with PCMA. MATERIALS AND METHODS: In this triple-blind clinical trial, a total of 34 patients, who were diagnosed with PCMA, treated using two different strategies of topical gabapentin as the active group and vehicle cream as the control group. RESULTS: Pruritus score reduction in both groups was statistically significant compared with the baseline value (p < 0.001). There was a significant pigmentation score reduction in intervention group compared with control group after 1 month of the study (p < 0.001). The differences of pigmentation score changes between the groups were not significant at month 2 (p = 0.52) and month 3 (p = 0.22). CONCLUSIONS: The results of this study suggest that topical gabapentin cream may be effective as a topical agent in the treatment of pruritus associated with PCMA without any significant adverse effects. It is recommended to perform similar studies with a larger sample size and longer duration in both sexes.

[Pharmacological Treatment of Trigeminal Neuralgia].

Although carbamazepine is the first-line treatment option for trigeminal neuralgia, it may not be sustained long-term. The benefits of carbamazepine are offset by adverse effects that lead to its withdrawal. The alternatives to carbamazepine include gabapentin, pregabalin, and microgabalin. Although used off-label in Japan, baclofen, lamotrigine, intravenous lidocaine, and botulinum toxin type A are also effective. Clinical experience has shown that alternative treatments are less effective than carbamazepine. Therefore, they can be used instead of or in addition to carbamazepine. The adverse effects of drugs include drowsiness, dizziness, rash, bone marrow suppression, and liver dysfunction. Carbamazepine and lamotrigine are particularly likely to cause severe drug eruptions such as Stevens-Johnson syndrome and toxic epidermal necrolysis. Low-dose titration is important to avoid the development of rashes and adverse effects.

Gabapentinoids and lactation: Review of the literature.

Gabapentin and pregabalin, which belong to the gabapentinoid drug family, are widely used, especially in neuropathic pain treatment, due to their effectiveness in pain management. Although many of the comorbidities and symptoms that limit the use of gabapentinoids are clearly described in the literature, there is limited data on their use during lactation. A 33-year-old female patient was admitted to our clinic with neuropathic pain and muscle weakness in her left lower extremity following spinal anesthesia for a cesarean section. We aimed to present the gabapentin treatment of a breastfeeding patient with persistent neuropathic pain in light of a literature review.

Update to Gabapentinoid Use in the United States, 2002-2021.

Gabapentinoids are commonly used medications for numerous off-label conditions. The 2002-2021 Medical Expenditure Panel Survey (MEPS) was used to investigate the proportion of the adult population who were gabapentinoid users, the ages of these users, medications and diagnoses associated with users, and the likelihood of starting, stopping, or continuing gabapentinoids. Gabapentinoid users continued to increase since our last publication from 4.0% in 2015 to 4.7% in 2021. Gabapentinoid use was much more likely among individuals who used other medications used in chronic pain. Between 2017-2021, numerous chronic pain conditions were associated with gabapentinoid use. New gabapentinoid users clearly outnumbered gabapentinoid stoppers between 2011-2012 and 2017-2018, but this difference decreased in the most recent cohorts.

Design and Synthesis of Dual-Targeting Inhibitors of sEH and HDAC6 for the Treatment of Neuropathic Pain and Lipopolysaccharide-Induced Mortality.

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.

Efficacy of Paravertebral Injection of Interferon-α2b Combined with High-Voltage, Long-Term Pulsed Radiofrequency in DRG in Mitigation of Postherpetic Neuralgia: A Retrospective Study.

OBJECTIVE: 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). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.