Drugs like duloxetine (Cymbalta) and pregabalin (Lyrica), approved for treating the painful disease fibromyalgia, don’t address inflammation, just the brain chemicals that may cause increased sensitivity to pain.

Dr. Hsu sees these drugs as “very promising for pain treatment. They work in a different way, to help you build up good neurotransmitters.”

There are many different types of drugs that fall under the general category of antidepressants used for treating pain. These include tricyclic antidepressants, serotonin and norepinephrine reuptake inhibitors (SNRIs), and, to a lesser extent, selective serotonin reuptake inhibitors (SSRIs). SSRIs may not relieve pain on their own, but enhance the pain-relief properties of tricyclic antidepressants. An anticonvulsant drug, pregabalin also appears useful for reducing pain.

Why these drugs work to reduce pain is still unclear, but they may increase neurotransmitters in the spinal cord that reduce pain signals reaching your brain. They don’t work immediately, and must be taken regularly over time to be effective. At this time, all are prescription drugs and in pill form.

For a localized area, such as one inflamed joint or a severely sore muscle, applying medication directly to the affected area through the skin can be a quick, convenient way to soothe pain. Topical agents, which include NSAIDs, sodium channel blockers and counterirritants, are available either over the counter or by prescription in stronger doses.

Topicals come in cream, gel, ointment, spray liquid or patch form. All deliver medicine through the skin at the affected area, bypassing the gastrointestinal system and therefore, reducing some stomach upset side effects caused by drugs like oral NSAIDs. Opioid patches also deliver medicine through the skin, but not in cream or gel form rubbed onto a single painful area.

In general, topicals cause few side effects if used locally. But because these rubs often contain strong medications that are absorbed into the bloodstream, using them in combination with oral versions of the same drugs can cause side effects or worsen them by upping the overall dosage of the drug.

Some common NSAIDs like aspirin, diclofenac and ibuprofen, which reduce the body’s production of prostaglandins that cause painful inflammation, are available as topicals. Counterirritants like cool-feeling menthol or hot-feeling capsaicin (the ingredient in chile peppers) are used for local joint or muscle pain. These agents cause the nerves in the area to become temporarily overwhelmed by heat or cool feelings, masking the pain.