The pain conductor: brainstem modulation in acute and chronic pain

Purpose of review It is well established in experimental settings that brainstem circuits powerfully modulate the multidimensional experience of pain. This review summarizes current understanding of the roles of brainstem nuclei in modulating the intensity of pain, and how these circuits might be recruited therapeutically for pain relief in chronic and palliative settings. Recent findings The development of ultra-high field magnetic resonance imaging and more robust statistical analyses has led to a more integrated understanding of brainstem function during pain. It is clear that a number of brainstem nuclei and their overlapping pathways are recruited to either enhance or inhibit incoming nociceptive signals. This review reflects on early preclinical research, which identified in detail brainstem analgesic function, putting into context contemporary investigations in humans that have identified the role of specific brainstem circuits in modulating pain, their contribution to pain chronicity, and even the alleviation of palliative comorbidities. The brainstem is an integral component of the circuitry underpinning pain perception. Enhanced understanding of its circuitry in experimental studies in humans has, in recent years, increased the possibility for better optimized pain-relief strategies and the identification of vulnerabilities to postsurgical pain problems. When integrated into the clinical landscape, these experimental findings of brainstem modulation of pain signalling have the potential to contribute to the optimization of pain management and patient care from acute, to chronic, to palliative states.