How people resolve pain: insights from human transcriptomics into immune activation and therapeutic innovations

Patients with chronic pain commonly exhibit elevated inflammatory markers in the blood that correlate with reported pain and pain-related disability. Although inflammation is traditionally seen as a driver of chronic pain, recent transcriptomic data challenge this view, highlighting the beneficial role of acute inflammation in pain resolution. Here, we present evidence pointing to the overall dynamics of the inflammatory response being critical for pain resolution with the initial acute inflammatory response necessary to trigger pain resolution processes. We posit that chronic pain reflects an inability to resolve inflammation rather than its mere presence. Pharmacological or nonpharmacological reactivation of acute inflammatory pathways may thus provide novel therapeutic strategies targeting pain resolution instead of merely mitigating pain perception. This novel hypothesis regarding the effect of inflammation on pain is an example of what can be learned using unbiased approaches such as human transcriptomics. We believe that the near future will feature more examples of hypothesis generation using human genetics followed up by mechanistic experimentation in animal models.