Cite as: Research grant updates. ASRA Pain Medicine News 2024;49. https://doi.org/10.52211/asra080124.012.

ASRA Pain Medicine offers several research grants annually. The recipients of the Carl Koller Memorial Research Grant, the Chronic Pain Medicine Research Grant, and the Early-Stage Investigator Award share an update on their progress in 2024.

Carl Koller Memorial Research Grant

Gina Votta-Velis and Alain Borgeat

Lidocaine Infusions in Pancreatic Cancer: Translational Studies in a Preclinical Model and Human Subjects

It is well known that local anesthetics have anti-inflammatory properties and that inflammation and cancer have common pathways.

Our team has always been interested in identifying a mechanism by which local anesthetics would have an antimetastatic effect. We have previously investigated the effect of amide local anesthetics on known mediators that are involved in inflammatory signaling and play a crucial role in cancer metastasis.

One of those mediators is SRC tyrosine-protein kinase (SRC), which is involved in signaling epithelial to mesenchymal transformation, promoting cell survival and mitogenesis, affecting the cytoskeleton remodeling for cell migration, and being a necessary factor for solid tumor metastasis.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignant disease, and it is well established that activation or elevated expression of SRC is frequently observed in PDAC and associated with a poor prognosis. As such, we decided to conduct a study on the effect of lidocaine infusions on pancreatic cancer.

Lidocaine Infusions in Pancreatic Cancer: Translational Studies in a Preclinical Model and Human Subjects

This human study is a double-blind, placebo-controlled, randomized clinical trial. (Registered in ClinicalTrials.gov)

• We are evaluating the effect of lidocaine infusions on the biology of the circulating tumor cells (CTCs) isolated from PDAC and genetically engineered KPC mice with PDAC.
• We have also conducted in vitro experiments with various pancreatic cell lines.
• During the manipulation of the tumor, even with non-touch techniques, there is the release of CTCs.
• We hypothesize that if lidocaine infusions attenuate SRC activation and phosphorylation in the CTCs, they will render them less aggressive and unable to go through the endothelial barrier of the blood vessels and form metastatic sites.

We continue recruiting patients for our clinical trial and proceeding with the analysis of the results without uncovering the blind. We expect that we will prove our hypothesis that lidocaine infusions affect the biology of tumor cells by attenuating SRC activation. We are also studying other molecules that contribute to the metastatic process. Subsequently, we can perform a study to evaluate survival in those patients.

Chronic Pain Medicine Research Grant

Paul Su

The Functional Role of Sensory Neuron ATF3 in Regulating Acute and Persistent Postsurgical Pain

As anesthesia providers, we are no strangers to managing acute postsurgical pain. However, chronic postsurgical pain (CPSP), pain that develops or worsens after a surgical procedure, is more challenging to manage with our current practices. Preoperative opioid use, the severity of acute pain, female sex, and pain catastrophizing are examples of clinical risk factors associated with the development of CPSP. However, the causality of these risk factors is unclear. With the support of the ASRA Chronic Pain Research Grant, we are trying to understand the biological mechanisms responsible for the development of CPSP. Our research integrates multiple tools to address this clinical gap, including genetically modified mice, deep sequencing, molecular biology, and animal behaviors.

Surgical incisions inevitably cut nerve endings, suggesting that recovery from nerve injury after surgery might play a key role in CPSP. Activating Transcription Factor 3 (ATF3) critically regulates neural regeneration after nerve injury. After hind paw incision surgery in mice, ATF3 is induced in the injured primary sensory neurons. Although ATF3 is induced after surgery, it does not play a role in acute pain because, even in ATF3 deficient mice, acute postsurgical pain behavior is unaffected. Interestingly, by two weeks after surgery, when acute pain resolves in mice (similar to humans), the ATF3-deficient mice continue to exhibit evidence of persistent pain. We use deep sequencing to analyze individual sensory neurons to identify genes and cellular pathways that may explain this observed behavior. Pain and nerve regeneration are appreciated as inextricably intertwined. However, based on our observations, we are excited to use this model system to distinguish between nerve regeneration-dependent (ATF3) and nerve regeneration-independent processes under acute and chronic settings. The outcomes will enhance our understanding of CPSP mechanisms, providing insights crucial for targeted therapeutic interventions to prevent and treat CPSP.

Early-Stage Investigator Award

Stephanie Pan

Utilization of Regional Anesthesia to Achieve Opioid-Sparing Pediatric Adenotonsillectomies

The supra zygomatic maxillary nerve (SZMN) block can assume a novel role in multimodal pain regimens for pediatric adenotonsillectomy surgeries, the second most common pediatric ambulatory surgery. Over 75% of children experience severe pain during the first three days following surgery, with clinically significant pain and negative behavior patterns lasting up to 2 weeks. Opioids are effective at treating pain, but their use must be judiciously balanced with the increased risk of airway obstruction and apnea. The SZMN block targets the maxillary division of the trigeminal nerve as it passes through the pterygopalatine fossa. From there, the maxillary nerve has many branches, including the lesser palatine nerve, which innervates a variable portion of the palatine tonsils, and the posterior palatine nerve, which innervates the adenoids. 

In our three-arm prospective, single-center, randomized controlled study, our primary aim is to determine if SZMN blocks, with and without dexmedetomidine, can decrease postoperative pain scores in the first 3 days following adenotonsillectomy. We hypothesize that the SZMN block will provide superior pain control compared to the current multimodal standard of care without any regional technique. In addition, we hypothesize that dexmedetomidine as a local anesthetic adjunct will extend pain relief for the first 3 postoperative days when pain is the most severe. Results from this study could improve the overall safety and recovery of pediatric patients undergoing adenotonsillectomy surgery by minimizing their opioid exposure and decreasing their risk of airway obstruction. In addition, the SZMN block could be extended to adults undergoing tonsillectomies and expanded to include more head and neck blocks in the day-to-day regional anesthesia armamentarium.