Simultaneous single-cell calcium imaging of neuronal population activity and brain-wide BOLD fMRI.

Regional anesthesia is a powerful perioperative tool, serving as the primary anesthetic and/or part of a multimodal pain management strategy. Regional anesthesia has been shown to reduce acute and persistent postoperative pain, and opioid consumption. However, 40–50% of patients experience acute worsening of pain upon the resolution of a single-injection nerve block. This phenomenon, termed “rebound pain,” typically lasts for 2–6 hours, and may be mitigated with additional multimodal analgesics, or largely prevented with a continuous nerve block catheter to prolong nerve block duration. One important mechanistic question is whether rebound pain reflects a true temporary resetting of the nociceptive system (hypersensitivity), or simply an unmasking of surgical pain as the nerve block wears off. However, distinguishing overt hypersensitivity secondary to a blocked state from a simple re-occurrence of postoperative pain is challenging in clinical settings, where surgical pain is present, and the trajectory of pain resolution varies among individuals. This study assessed nociceptive sensitivity in healthy volunteers across the entire time course of a single-injection axillary brachial plexus block, from careful assessment of baseline out to 3-hours after nerve block resolution. We investigated whether participants experienced heightened sensitivity to heat and pressure pain, or changes in central sensitization, in the absence of a surgical incision. The primary outcome was the difference in heat pain threshold at 60-minutes after full motor resolution, compared between the block and control arms. The null hypothesis was that no difference in sensitivity would be observed between block and control arms, consistent with the contention that rebound pain reflects the relatively sudden unmasking of surgical pain following nerve block resolution, rather than frank nociceptive sensitization.