Abstract: Provided herein are compositions containing an antibody or antigen-binding antibody fragment that specifically binds to metallothionein 2 (MT2) protein, and compositions containing an agent that binds to or neutralizes a function of MT2 protein and/or an oligonucleotide that decreases the expression of MT2 mRNA in a mammalian cell, and optionally, one or more anti-inflammatory agents and/or analgesics. Also provided are methods of decreasing pain in a mammal that include administering to the mammal an agent that binds to or neutralizes a function of MT2 protein and/or an oligonucleotide that decreases the expression of MT2 mRNA in a mammalian cell, in an amount sufficient to decrease the level of extracellular MT2 protein or neutralize a function of extracellular MT2 protein in the mammal, thereby decreasing pain in the mammal.