Basis for a clinical trial to assess and manipulate locus coeruleus function to speed recovery after surgery. (A) The underlying hypothesis is that (1) episodic pain with movement after surgery enters the spinal cord and is amplified by central sensitization before (2) transmission to the locus coeruleus. The locus coeruleus responds (3) with transient bursting of activity in descending projections to the spinal cord, which results over weeks in resolution of central sensitization and postoperative pain. (B) The Frank–Starling relationship between end-diastolic volume and cardiac stroke volume in patients with heart failure. At low end-diastolic volume, shown in green, intravenous (IV) fluid increases stroke volume, whereas at high end-diastolic volume, shown in red, IV fluid exacerbates heart failure and decreases stroke volume. (C) Hypothesized relationship between tonic activity of the locus coeruleus and phasic response to a pain stimulus and the influence of gabapentin. At low rates of tonic locus coeruleus activity, shown in green, gabapentin (which increases tonic locus coeruleus activity) increases the phasic response to intermittent pain, whereas with high resting tonic locus coeruleus activity, shown in red, gabapentin would decrease the acute response to pain.