I know this topic has been appearing from time to time without any answer. I don't want to add to this bug's "noise". I'd rather like to report my findings, hoping that it could help Textpad developpers find the solution.
There're many ways to open a file inside TextPad. Here are three of them:
1. Right-click on a file to popup the context menu and choose "TextPad" menu item.
2. Select the file first (using single mouse click or keyboard). Press keyboard's "Context menu" key (usually between right windows key and right control key, for those who don't know where it is) and choose "TextPad".
3. Select the file first. Open "File" menu of Windows Explorer and choose "TextPad".
Only method 1 will lock up the mouse up in the explorer window from which the file is opened but not 2 or 3. Actually, saying "lock up" isn't totally correct. The mouse can move. It can also open any menu. Even the button bar is responsive to mouse click. It's just that any click event (left, middle or right) isn't "transfered" to the zone where there're files and folder. Even the left pane elements are responsive.
Hope this could reduce the problem scope to TextPad developpers and help them debug quickly.
Partial solution
I've found a partial solution and would like to share with others. When such mouse "lockup" problem happens, click on the button bar to go up or go down one directory and come back. That would unfreeze the mouse click problem.
Mouse lockup when using file's context menu TextPad
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