Pain state modulation of emergence from anesthesia

The National Institute of General Medical Sciences, part of the National Institutes of Health at the Department of Health and Human Services, awarded $236,652 to the University of Washington on August 21, 2026, under the Biomedical Research and Research Training program (CFDA 93.859) to fund research on how chronic pain modulates emergence from general anesthesia.

The research will characterize how pain state alters neural activity and behavioral responses during anesthetic emergence using a mouse model of neuropathic pain (partial sciatic nerve ligation). The work consists of two primary aims: first, to characterize cell-specific endogenous activity in the nucleus accumbens during emergence in the context of chronic pain using 1-photon calcium imaging to examine distinct neuronal populations (D1 and D2 neurons); second, to examine how activation and inactivation of neurons projecting from the ventral tegmental area to the nucleus accumbens affect emergence behavior across different pain states using chemogenetic approaches. These studies aim to identify changes in neural circuit activity that could inform interventions to accelerate emergence from anesthesia and mitigate negative outcomes such as post-anesthetic delirium and agitation in patients with chronic pain.

The University of Washington Office of Sponsored Programs is the recipient organization. Performance is located in Seattle, Washington, with a completion date of June 15, 2028. The assistance type is Project Grant.

Abstract

General anesthesia is widely used in a host of procedures and surgeries, but emergence is still a passive process without active interventions. There are currently no methods for accelerating emergence from an anesthetized state and few options for mitigating negative outcomes of emergence, like delirium and agitation. Emergence agitation and delirium is further complicated by the existence of a chronic pain state in many patients undergoing anesthesia. The nucleus accumbens (NAC) regulates emergence from anesthesia, and NAC is a hub for systems controlling pain processing, mood, and reward. This suggests that emergence may be affected by a host of different affective states, including pain and pain management therapies such as opioid drugs. Previous research has identified VTA activity as a key component in arousal and has established the role of the NAC in emergence from anesthesia. What remains unclear is how different affective states, such as pain, modulate this activity. My proposal endeavors to demonstrate how pain changes behavior and neural activity during emergence from general anesthesia, using a well-established mouse model of neuropathic pain, partial sciatic nerve ligation (psnl). I will determine how pain state alters emergence behavior and NAC circuit activity. In aim 1, i will characterize cell-specific endogenous activity in the NAC during emergence in the context of chronic pain. Using 1-photon calcium imaging in D1 and D2 neurons to examine how these distinct neuronal populations respond during both pain and emergence behavior. In aim 2, i will examine the effects of activation and inactivation of neurons projecting from the VTA to NAC on emergence. Using chemogenetic approaches, i will determine how this critical reward pathway modulates emergence and post-anesthetic behavior in different pain states these studies will identify changes in NAC neural activity and VTA to NAC projections modulating emergence in the context of pain. These findings will provide a basis for further mechanistic studies of the effect of pain state on emergence toward the goal of improving perioperative care for chronic pain patients.