Methods and compositions for therapy of pain are provided. Compositions comprising therapeutically effective amounts of two or more of an extract of Ganoderma lucidum, an extract of Salvia miltiorrhiza and an extract of Scutellaria barbata and optionally a therapeutically effective amount of an extract of Hippophae rhamnoides are provided. Novel synergistic effects of the use of these compounds in combination therapy are disclosed. Compositions exhibit multiple functions that are useful for the treatment of pain and inflammation. Compositions of the invention inhibit the activity of COX-2 to a greater extent than COX-1. Compositions of the invention also inhibit the nuclear accumulation of NF-kappaB and thus inhibit the expression of a number of proinflammatory molecules including COX-2.