Genetic Study Identifies New Target for Treating Post-Surgical Pain

A study in Anesthesiology suggests a new target for pain control in patients who develop chronic pain after surgery. The target, spinal cathepsin G (CTSG), is a pro—nociceptive mediator in both an animal model and human study. The research points to the potential for inhibiting CTSG through an inhibitor.

The finding is important because chronic postsurgical pain can severely affect quality of life and occurs in at least 10% of patients undergoing common surgical operations, such as hernia repair, mastectomy, and joint replacement surgery. Despite a wealth of clinical research on the topic and the breadth of the problem, there is no consensus for managing chronic postsurgical pain.

Earlier research has suggested that proteases function as modulators of pain-related cytokines and chemokines, and some stud has shown that central sensitization plays an essential role in the development of chronic pain in patients who undergo surgery. The researchers posited that blocking CTSG could reduce inflammation in the spinal cord.

The study involved a microarray analysis of rats with persistent hyperalgesia after intraplantar injection of complete Freund’s adjuvant (n=4). The analysis identified CTSG as the most up—regulated gene in these subjects. Then, the researchers evaluated the association between CTSG gene polymorphisms and the risk of chronic postsurgical pain in 1,152 surgical patients. In the gene association study, 246 patients (21.4%) reported chronic postsurgical pain at 12—month follow–up.

Promising results suggested that targeting proteases may therefore represent a new approach to regulate nociceptive transmission in the spinal cord. “Inhibition of CTSG attenuated chronic inflammation-associated hyperalgesia, and this was accompanied with a decrease in neutrophilic infiltration and a lower level of IL-1β in the spinal dorsal horn,” the study authors noted. “We further demonstrated the relevance of CTSG gene polymorphisms in the development of chronic postsurgical pain. The risk of chronic postsurgical pain was significantly reduced in patients carrying homozygous A alleles of SNP rs2236742 or rs2070697 in the CTSG gene. Taken together, our data suggest that CTSG odulates pain hypersensitivity and is a potential target for pain management.”

In addition to CTSG polymorphisms, the researchers found that male patients and patients under the age of 65 were at a higher risk for chronic postsurgical pain. “Patients reporting severe pain early after surgery also tended to develop chronic postsurgical pain, but this did not reach statistical significance in our multivariate model,” they wrote.

The researchers suggest that not only can CTSG be a potential for chronic pain intervention, but that preoperative determination of CTSG gene polymorphisms may facilitate perioperative physicians to formulate an appropriate plan to prevent chronic postsurgical pain.