Substitute will block Pain Split. Substitute blocks the following moves >
> After You, Bestow, Block, Captivate, Charm, Confuse Ray, Cotton Spore, Dark Void, Entrainment, Fake Tears, FeatherDance, Flash, Flatter, Gastro Acid, Glare, GrassWhistle, Growl, Guard Split, Heal Pulse, Hypnosis, Kinesis, Leech Seed, Leer, Lock-On, Lovely Kiss, Mean Look, Metal Sound, Mind Reader, Nightmare, Pain Split, Poison Gas, PoisonPowder, Power Split, Psycho Shift, Quash, Sand-Attack, Scary Face, Screech, Simple Beam, Sing, Sky Drop, Sleep Powder, SmokeScreen, Soak, Spider Web, Spore, String Shot, Stun Spore, Supersonic, Swagger, Sweet Kiss, Sweet Scent, Switcheroo, Tail Whip, Teeter Dance, Telekinesis, Thunder Wave, Tickle, Toxic, Transform, Trick, Will-O-Wisp, Worry Seed, Yawn. It does not, however, block any other non-attacking move effects.
The above from Smogon's Substitute page.
So no, Pain Split will fail in this case.
