Articles: neuralgia.
-
Review Meta Analysis
Neuropathic pain clinical trials: factors associated with decreases in estimated drug efficacy.
Multiple recent pharmacological clinical trials in neuropathic pain have failed to show beneficial effect of drugs with previously demonstrated efficacy, and estimates of drug efficacy seems to have decreased with accumulation of newer trials. However, this has not been systematically assessed. Here, we analyze time-dependent changes in estimated treatment effect size in pharmacological trials together with factors that may contribute to decreases in estimated effect size. ⋯ Several factors that changed over time, such as larger study size, longer study duration, and more studies reporting 50% or 30% pain reduction, correlated with the decrease in estimated drug effect sizes. This suggests that issues related to the design, outcomes, and reporting have contributed to changes in the estimation of treatment effects. These factors are important to consider in design and interpretation of individual study data and in systematic reviews and meta-analyses.
-
Randomized Controlled Trial
The Analgesic and Emotional Response to Intravenous Lidocaine Infusion in the Treatment of Postherpetic Neuralgia: A Randomized, Double-Blinded, Placebo-controlled Study.
This study evaluated the analgesic efficacy and emotional response to intravenous lidocaine infusion compared with placebo in patients with postherpetic neuralgia (PHN). ⋯ The analgesic response of 5 mg/kg lidocaine intravenous infusion is comparable to placebo in patients with PHN, but intravenous lidocaine infusion significantly reduced total analgesic consumption, and improved the overall emotional and health status.
-
Recently, (±)-N-(3-fluoro-1-phenethylpiperidine-4-yl)-N-phenyl propionamide (NFEPP), a newly designed μ-opioid receptor (MOR) agonist with a low pKa, has been shown to produce injury-restricted analgesia in models of inflammatory and postoperative pain, without exhibiting typical opioid side effects. Here, we investigated MOR binding of NFEPP in brain and dorsal root ganglia, pH in injured tissues, and the analgesic efficacy of NFEPP compared with fentanyl in a chronic constriction injury model of neuropathic pain, and in the acetic acid-induced abdominal writhing assay in rats. Binding experiments revealed significantly lower affinity of NFEPP compared with fentanyl at pH 7.4. ⋯ Intravenous NFEPP as well as fentanyl dose-dependently diminished neuropathy-induced mechanical and heat hypersensitivity, and acetic acid-induced abdominal constrictions. In both models, NFEPP-induced analgesia was fully reversed by naloxone methiodide, a peripherally restricted opioid receptor antagonist, injected at the nerve injury site or into the abdominal cavity. Our results indicate that NFEPP exerts peripheral opioid receptor-mediated analgesia exclusively in damaged tissue in models of neuropathic and abdominal pain.
-
This study investigated the characteristics of temperature-related evoked neural activities to baseline skin temperatures on target and adjacent sites using contact heat evoked potentials (CHEPs). ⋯ This study using CHEPs shows the importance of baseline and target skin temperatures to investigate the characteristics of temperature-related neural activities. This measure may contribute to understanding of warm-, hot-, and pain-related neural activities in human brains.
-
We have previously demonstrated that lysophosphatidic acid (LPA) plays key roles in the initial mechanisms for neuropathic pain (NeuP) development. Here, we examined whether LPA receptor mechanisms and LPA production are related to the glial activation at a late stage after partial sciatic nerve ligation (pSNL) by use of microglial inhibitor, Mac1-saporin or astrocyte inhibitor, and L-α-aminoadipate (L-AA). Although single intrathecal injection of LPA1/3 antagonist, Ki-16425 did not affect the pain threshold at day 7 after the spinal cord injury, repeated treatments of each compound gradually reversed the basal pain threshold to the control level. ⋯ The involvement of LPA receptors in astrocyte activation in vivo was evidenced by the findings that Ki-16425 treatments abolished the upregulation of CXCL1 in activated astrocytes in the spinal dorsal horn of mice at day 14 after the pSNL, and that Ki-16425 reversed the LPA-induced upregulation of several chemokine gene expressions in primary cultured astrocytes. Finally, we found that significant hyperalgesia was observed with intrathecal administration of primary cultured astrocytes, which had been stimulated by LPA in a Ki-16425-reversible manner. All these findings suggest that LPA production and LPA1/3 receptor activation through differential glial mechanisms play key roles in the maintenance as well as initiation mechanisms in NeuP.