Background and Objectives: Upper abdominal pain is a dominant feature of chronic pancreatitis. A key phenomenon in this context is hyperalgesia, typically associated with N-methyl-d-aspartate receptor activation. This exploratory study evaluates acute effects of S-ketamine, a noncompetitive N-methyl-d-aspartate antagonist, in modulating generalized hyperalgesia in chronic pancreatitis pain.

Methods: In a blinded crossover trial, 10 chronic pancreatitis pain patients received S-ketamine for 3 hrs at 2 μg · kg⁻¹ · min⁻¹ or placebo infusion at an equivalent rate in randomized order. Clinical pain was assessed via visual analog scale (VAS) and short Dutch Language Version McGill Pain Questionnaire (sf-MPQ-DLV). Pressure pain thresholds (PPTs) were measured in dermatome C5, T4, dorsal T10, L1, and L4, and the sum of PPTs (SOPPT) calculated before, at end of, and after infusion.

Results: Nine patients completed the study. Median pain VAS before infusion was 29 mm at rest, 32 mm during activity; sf-MPQ-DLV score was 4. For the S-ketamine session median SOPPT change at infusion end was significantly higher than in the placebo session (218; interquartile range [IQR], 116-527, versus −123 [IQR, −330 to 24]; P = 0.005) and significant versus preinfusion values (2109 [IQR, 964-3035] vs 1914 [IQR, 842-2884]; P = 0.03). The SOPPT was unchanged versus preinfusion values and similar between groups at 1 hr after infusion end. No significant changes in VAS and sf-MPQ-DLV occurred.

Conclusions: S-ketamine infusion is more effective than placebo in increasing PPTs in chronic pancreatitis pain patients immediately after infusion. This effect did not outlast the infusion. Further research is warranted into S-ketamine use for reducing generalized hyperalgesia and chronic pancreatitis pain.