The effects of transcranial electrical stimulation of the left dorsolateral prefrontal cortex on tactile spatial discrimination performance.

The dorsolateral prefrontal cortex (DLPFC) plays a key role in tactile perceptual discrimination performance. Both transcranial random noise stimulation (tRNS) and anodal transcranial pulsed current stimulation (tPCS) have been shown to modulate neural activity in cortical regions. In this study, we aimed to determine whether tRNS and anodal tPCS over the left DLPFC would improve tactile perceptual discrimination performance of the right index finger in healthy neurological individuals. Subjects underwent a grating orientation task before, immediately after, and 30 min after applying tRNS in Experiment 1 or anodal tPCS in Experiment 2. tRNS application on the left DLPFC tended to enhance tactile perceptual discrimination performance. In contrast, the application of anodal tPCS over the left DLPFC did not affect tactile perceptual discrimination performance. These findings indicate that transcranial electrical stimulation to the left DLPFC may improve tactile perceptual discrimination performance, with effects that depend on stimulus modality.

Antinociceptive activity of the novel RAGE inhibitor, papaverine, in a mouse model of chronic inflammatory pain.

Extracellular high-mobility group box 1 (HMGB1) is known to mediate the inflammatory response through pattern recognition receptors, including the receptor for advanced glycation end products (RAGE) or the toll-like receptors (TLRs). The aim of the present study was to investigate whether papaverine, a novel RAGE inhibitor, could suppress inflammatory pain in mice after several time points, which was induced by the injection of complete Freund's adjuvant (CFA). We also investigated the influence of redox modulation during a state of chronic inflammatory pain. Although papaverine did not suppress CFA-induced mechanical allodynia on Day 7, papaverine significantly suppressed CFA-induced mechanical allodynia on Days 14 and 28. In contrast, the radical scavenger N-tert-Butyl-α-phenylnitrone (PBN) suppressed mechanical allodynia in mice on Days 7 and 14, but not on Day 28. We demonstrated that the RAGE inhibitor improves mechanical allodynia in chronic inflammatory conditions. Moreover, we also found that high levels of reactive oxygen species (ROS) contributed to the early phase of CFA-induced mechanical allodynia. Precisely, lower ROS levels contributed to the inflammatory pain response via the all-thiol HMGB1/RAGE signaling pathway during the chronic state. These findings led us to propose that ROS levels modulate RAGE and/or TLR4-mediated inflammatory allodynia by regulating the concentrations of disulfide HMGB1 or all-thiol HMGB1.

Evaluation of the antinociceptive activities of several sodium channel blockers using veratrine test in mice.

An important role of voltage-gated sodium channels (VGSCs) in many different pain states has been established in animal models and humans wherein sodium channel blockers partially ameliorate pain. However, behavioral tests for screening analgesics that exhibit pharmacologic action by acting on VGSCs are rarely reported, and there are no studies on antinociception using veratrine as a nociceptive agent. The aim of the present study was to examine the amount of nociceptive behavior evoked by subcutaneous administration of veratrine into the hind paw and investigate whether veratrine can be used as a VGSC agonist to test the pharmacological properties of candidate analgesics via sodium channel blockade. We report for the first time that intraplantar injection of veratrine produced a reproducible nociceptive response in mice. Furthermore, several sodium channel blockers, namely carbamazepine, valproate, mexiletine, and the selective Nav1.7 inhibitor PF-04856264, but not flecainide or pilsicainide, reduced veratrine-induced nociception. In contrast, calcium channel blockers gabapentin and ethosuximide did not change veratrine-induced nociception. The veratrine test in mice might be a useful tool, at least in part, to evaluate the potential analgesic effect of sodium channel blockers.