A method is provided for using .alpha..sub.2.delta. subunit calcium channel modulators or other compounds that interact with the .alpha..sub.2.delta. calcium channel subunit in combination with one or more compounds with smooth muscle modulatory effects to treat pain. According to the present invention, .alpha..sub.2.delta. subunit calcium channel modulators include GABA analogs (e.g., gabapentin and pregabalin), fused bicyclic or tricyclic amino acid analogs of gabapentin, and amino acid compounds. Compounds with smooth muscle modulatory effects include antimuscarinics, .beta.3 adrenergic agonists, spasmolytics, neurokinin receptor antagonists, bradykinin receptor antagonists, and nitric oxide donors.