The effect of hand therapy on alleviating chemotherapy-induced peripheral neuropathy in a model mouse.

The use of neurotoxic chemotherapeutic agents induces numbness in the limbs through chemotherapy-induced peripheral neuropathy (CIPN). Recently, we found that hand therapy involving finger massage improved mild to moderate numbness in CIPN patients. In this study, we behaviorally, physiologically, pathologically, and histologically investigated the mechanisms underlying hand therapy-induced numbness improvement in a CIPN model mouse. Hand therapy was performed for 21 days after the disease induction. Its effects were evaluated using mechanical and thermal thresholds and blood flow in the bilateral hind paw. Moreover, 14 days after the hand therapy was administered, we assessed the blood flow and conduction velocity in the sciatic nerve, the level of serum galectin-3, and the histological myelin and epidermis-related changes in the hindfoot tissue. Hand therapy significantly improved allodynia, hyperalgesia, blood flow, conduction velocity, serum galectin-3, and epidermal thickness in the CIPN model mouse. Furthermore, we observed the images of repairs of the myelin degeneration. Thus, we found that hand therapy could improve numbness in the CIPN model mouse and that it could help to repair peripheral nerves by promoting blood circulation in the limbs.

Evaluation of in vitro transdermal permeation, mass spectrometric imaging, and in vivo analgesic effects of pregabalin using a pluronic lecithin organogel formulation in mice.

In clinical practice, pregabalin is orally administered for neuropathic pain, but causes severe central nervous system side effects, such as dizziness, which results in dose limitation or discontinuation. To reduce the central side effects of pregabalin, we developed four pregabalin preparations for transdermal application: 0.4% aqueous solution, pluronic lecithin organogel (PLO gel), hydrophilic cream, and lipophilic cream. Transdermal permeabilities of pregabalin among the four formulations were compared in vitro using hairless mouse skin. The longitudinal distribution of pregabalin within the skin was analyzed using mass spectrometric (MS) imaging. Furthermore, the in vivo analgesic effects of the formulations were evaluated using the von Frey filament test in a mouse model of diabetic neuropathy (DN). The PLO gel showed the highest permeability of pregabalin, followed by the aqueous solution, and no permeation was observed in the two cream formulations. The MS imaging analysis showed that pregabalin was distributed up to the dermis in the PLO gel 1 h after application, while the aqueous solution was distributed near the epidermis. A significant analgesic effect (p < .05) was observed 1.5 h after PLO gel application in the DN model mice, but the aqueous solution had no effect. This study indicated for the first time that pregabalin penetrated beyond the skin epidermis up to the dermis, from the PLO gel formulation, and that the application of this formulation exhibited an in vivo analgesic effect in the mouse model of DN.