Roughly 110,000 Americans died from a drug overdose between February 2021 and February 2022. That figure is part of a larger troubling trend. Life expectancy in the U.S. fell in 2020 and again in 2021, after decades of progress. Deaths linked to alcohol, drugs, and suicide are a major part of that change. Overdoses, suicides and other "deaths of despair" ... have been climbing since the 1990s and may have accelerated in recent years. Losing a job, recovering from an accident or illness, and experiencing divorce or financial difficulties may trigger desperation. People may use drugs and alcohol to ease these uncomfortable mental states. Scientific evidence shows that one common denominator in this cycle of stress, anxiety, depression and substance abuse is physical pain. The relationship between despair and pain is multifaceted. As most people know from personal experience, physical pain increases psychological distress and anxiety. The reverse relationship is also possible: psychological distress can cause physical pain. When someone is in a negative mood, researchers have found, the brain areas that play a role in physical pain also engage. The opioid epidemic may be the most prominent example of how physical pain and despair interact. The misuse of painkillers, especially opioids, generates changes in the brain that trigger higher pain sensitivity, as well as greater tolerance of and addiction to these drugs. As a result, people are more likely to overdose on these medications.