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The Center for Disease Control and Prevention estimates that 75% of reported cases of traumatic brain injury (TBI) are mild, where chronic pain and depression are 2 of the most common symptoms. In this study, we used a murine model of repeated mild TBI to characterize the associated pain hypersensitivity and affective-like behavior and to what extent microglial reactivity contributes to these behavioral phenotypes. Male and female C57BL/6J mice underwent sham or repeated mild traumatic brain injury (rmTBI) and were tested for up to 9 weeks postinjury, where an anti-inflammatory/neuroprotective drug (minocycline) was introduced at 5 weeks postinjury in the drinking water. Repeated mild traumatic brain injury mice developed cold nociceptive hypersensitivity and negative affective states, as well as increased locomotor activity and risk-taking behavior. Minocycline reversed negative affect and pain hypersensitivities in male but not female mice. Repeated mild traumatic brain injury also produced an increase in microglial and brain-derived neurotropic factor mRNA transcripts in limbic structures known to be involved in nociception and affect, but many of these changes were sex dependent. Finally, we show that the antiepileptic drug, gabapentin, produced negative reinforcement in male rmTBI mice that was prevented by minocycline treatment, whereas rmTBI female mice showed a place aversion to gabapentin. Collectively, pain hypersensitivity, increased tonic-aversive pain components, and negative affective states were evident in both male and female rmTBI mice, but suppression of microglial reactivity was only sufficient to reverse behavioral changes in male mice. Neuroinflammation in limbic structures seems to be a contributing factor in behavioral changes resulting from rmTBI.

Background: Renal colic is characterized by severe pain that is highly disabling. Gabapentin, an antiepileptic medication, is often recommended as a first-line therapy for neuropathic pain. However, its effectiveness in managing somatic pain, which is defined as the result of activity by pain receptors in the deep tissues, such as renal colic pain, is not as well-established. Method: A phase 3 randomized clinical trial was conducted to evaluate the adjuvant analgesic effects of gabapentin on acute renal colic pain. Eligible patients participated in the study via random allocation to the control or gabapentin groups using the block randomization method. All patients received a shared regimen of ketorolac and rescue morphine as the conventional analgesic treatment for renal colic pain. Gabapentin was added as an adjuvant analgesic for the gabapentin group. Result: A total of 63 individuals with an average age of 41.35 ± 13.08, were enrolled and completed the study. At the time of admission, there were no significant differences between the baseline characteristics of two groups, with exception of weight. The gabapentin group showed a significantly higher percentage of patients with pain severity of less than 5 after 60 and 90 min, as well as a significantly lower percentage of morphine rescue requirement and total morphine intake (mg) and mg/kg. Conclusion: In cases of acute renal colic, gabapentin significantly decreases both the amount of morphine required and the degree of pain, indicating that it may be a useful adjutant to standard analgesic regimens. Treatment regimens that include gabapentin may help individuals manage their pain and become less reliant on opioids. Clinical Trial Registration: https://irct.behdasht.gov.ir/trial/56066 , identifier: IRCT20200322046833N2. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to prepare cholesterol and stearic acid-based solid lipid nanoparticles of gabapentin (GAB-SLNs) for protection against streptozotocin (STZ)-induced retinal injury in rats. Methods: We prepared four preparations of GAB-SLNs using a hot high-shear homogenization ultrasonication process, and the best formulation was selected and tested for biological activity. The retinal injury was brought in male adult albino rats while gabapentin doses continued for 6 weeks. Six groups of rats were assigned as the vehicle, diabetic, diabetic + gabapentin (10–20 mg/kg), and diabetic + GAB-SLNs (10–20 mg/kg). GAB-SLN#2 was selected as the optimized formulation with high entrapment efficacy (EE%, 98.64% ± 1.97%), small particle size (185.65 ± 2.41 nm), high negative Zeta potential (−32.18 ± 0.98 mV), low polydispersity index (0.28 ± 0.02), and elevated drug release (99.27% ± 3.48%). The TEM image of GAB-SLN#2 revealed a smooth surface with a spherical shape. Results: GAB-SLNs provided greater protection against retinal injury than free gabapentin as indicated by the histopathology data which demonstrated more organization of retinal layers and less degeneration in ganglion cell layer in rats treated with GAB-SLN#2. Further, GAB-SLN#2 reduced the inflammatory proteins (IL-6/JAK2/STAT3) and vascular endothelial growth factor (VEGF). Conclusion: The preparation of GAB-SLNs enhanced the physical properties of gabapentin and improved its biological activity as a neuroprotectant. Further studies are warranted to validate this technique for the use of oral gabapentin in other neurological disorders. [ABSTRACT FROM AUTHOR]

Background: Perioperative anxiety adversely affects mental and physical well-being and it is associated with increased pain, stressor responses with general anesthesia (GA), and nauseavomiting leading to delayed recovery. Recent studies have proven melatonin and gabapentin provide sedation, anxiolysis, and reduced pressure responses. Aims and Objectives: This study aimed to compare melatonin and gabapentin as premedication for anxiolysis and attenuation of hemodynamic response to GA. Post-operative pain and sedation were also compared. Materials and Methods: A total of 99 subjects (n=33 in each group) between 18 and 60 year of age, ASA I/II scheduled for elective abdominal surgeries of < 3h under GA were included in the study. Patients in Group A were administered melatonin (10 mgx2 tab.), those in Group B were administered gabapentin (400 mgx2 tabs), and those in control Group C were treated with Vitamin C (500 mgx2) before 2 h of surgery. At 0 min, 30 min, and 60 min assessments of anxiety, sedation, cognition, psychomotor function, and orientation were done. Results: There were significantly low anxiety scores in Groups M and G compared to Group C at 60 min and 90 min (P=0.0000). Sedation score was significantly less in Group C patients compared to Group M and G at 30 min (P=0.0008), 60 min, and 90 min (P=0.0000) intervals. Heart rate and mean arterial pressure were increased in Group C patients as compared to Groups M and G. Conclusion: This study showed that melatonin had more anxiolytic and less sedative action, so also cognitive functions and orientation were well preserved in melatonin-treated subjects than in gabapentin. Hemodynamic responses were comparable in melatonin- and gabapentin-treated patients. [ABSTRACT FROM AUTHOR]