Pharmaceutical compositions and their methods of use

1. A method for treating pain in a patient, comprising:

(i) administering an amount of nicotinic acetylcholine receptor ligand to the patient, wherein the nicotinic acetylcholine receptor ligand is 5[(2R)-azetidin-2-ylmethoxy]-2-chloropyridine; and

(ii) administering an amount of nicotinic acetylcholine receptor subtype α4β2 positive allosteric modulator to the patient, wherein the nicotinic acetylcholine receptor subtype α4β2 positive allosteric modulator has the formula:

or is a pharmaceutically acceptable salt thereof, wherein

Ar 2 is phenyl or pyridinyl, wherein the phenyl or pyridinyl is substituted or unsubstituted, and, when substituted, the phenyl or pyridinyl is substituted with 1, 2, 3, or 4 substituents selected from halo, C 1 -C 6 haloalkyl, C 6 -C 10 aryl, C 4 -C 7 cycloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 5 -C 10 heteroaryl, C 4 -C 10 heterocycle, C 1 -C 6 alkyl, —(C 1 -C 6 alkyl)NHC(O)O—(C 1 -C 6 alkyl), C 1 -C 6 hydroxyalkyl, C 1 -C 6 alkylcarbonyl, amino, hydroxyl, haloalkyl-C(O)—, haloalkyl-SO 2 —, alkyl-SO 2 —, —SO 2 NH 2 , —SO 2 NH(C 1 -C 6 alkyl), —SO 2 N(C 1 -C 6 alkyl) 2 , cyano, nitro, C 1 -C 6 acylamino, C 1 -C 6 alkoxy, —C(O)NH 2 , —C(O)O—(C 1 -C 6 alkyl), and carboxy; and

Ar 3 is phenyl or pyridinyl, wherein the phenyl or pyridinyl is substituted or unsubstituted, and, when substituted, the phenyl or pyridinyl is substituted with a substituent selected from halo, C 1 -C 6 haloalkyl, C 6 -C 10 aryl, C 4 -C 7 , cycloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 5 -C 10 heteroaryl, C 1 -C 6 alkyl, C 1 -C 6 hydroxyalkyl, amino, hydroxyl, haloalkyl-SO 2 —, cyano, nitro, C 1 -C 6 acylamino, C 1 -C 6 alkoxy, —N(C 1 -C 6 alkyl) 2 , and carboxy; and

wherein the amounts of (i) and (ii) together are more effective in treating pain.

2. The method of claim 1 , further comprising administering a pain medication comprising a compound selected from an opioid, gabapentin, pregabalin, duloxetine, a cannabinoid ligand, a vaniolloid receptor antagonist, calcium channel blocker and a sodium channel blocker.

3. The method of claim 1 , wherein Ar 2 is substituted pyridinyl, unsubstituted pyridinyl, or substituted phenyl; and Ar 3 is substituted pyridinyl, unsubstituted pyridinyl, or substituted phenyl; wherein the pyridinyl group, when substituted, is substituted with fluoro and the phenyl group is substituted with cyano, sulfonamide, or fluoro.

4. The method of claim 3 , wherein Ar 3 is cyanophenyl and Ar 3 is pyridin-3-yl.

5. The method of claim 1 , wherein the nicotinic acetylcholine receptor subtype α4β2 positive allosteric modulator is 3-(3-(pyridin-3-yl)-1,2,4-oxadiazol-5-yl)benzonitrile.