Correlation between CGRP Levels and the Neuropathic and Inflammatory Component of Postoperative Pain

Abstract

Introduction: In surgical procedures, tissue damage results in the release of a number of bioactive substances. Calcitonin gene-related peptide (CGRP) is a peptide released from sensory nerves, which determines its role in pain sensation. Its distribution in tissues deter­mines its role as a primary afferent neurotransmitter. Aim: To determine the effect of CGRP on postoperative pain and reactive inflammatory process after surgical removal of impacted mandibular third molars, as well as the factors that have influence upon the perception of pain. Materials and methods: Forty patients with bilaterally impacted mandibular third molars were included in the study. Venous blood samples were collected before and 24 hours after the surgical procedure in order to test their serum levels of CGRP and procalcitonin. Two weeks later the procedure was repeated. The difficulty of the surgical procedure, its duration and complications were assessed in all patients. Results: The influence of some of the studied factors upon postoperative pain was established. Differences in the sensation of pain between the two sexes were found when comparing pain intensity reported by the patients. Significant difference between pain inten­sity after the 1st and 2nd surgical procedures (6 hours) was found in females (Z=2.63, p=0.009;), whereas in males the difference was observed at 24 hours (Z=1.99; p=0.047). Regarding the existence of sex-related association, а significant, strong positive correlation between CGRP levels after the 1st and 2nd surgical procedures (24 hours) was found in males (rxy=0.78; p=0.004), whereas in females this correlation was also significant, although moderately significant (rxy=0.44; p=0.020). CGRP levels at the first and second extractions were generally similar in males, and not as much in females. We proved significantly moderate positive association between CGRP and pulse levels measured before the second surgery (rxy=0.37, p=0.021). Conclusion: The results of our study suggest a significant role of CGRP in reactive (neurogenic) inflammation.

CGRP measurements in human plasma – a methodological study

“…This amount of CGRP was obviously fully removed by pre-absorption, so that this plasma could be used for measuring the CGRP content in the individual plasma samples. Human plasma may contain high levels of CGRP due to other reasons of very different pathologies, for example sepsis ( 35 ), endocrine tumors ( 36 ), acute psoriasis ( 37 ) or severe pain states ( 38 , 39 ) other than headaches. Nerve regeneration is accompanied by a high expression of CGRP ( 40 ), which could possibly contribute to elevated plasma levels.…”

Research Progress in Calcitonin Gene-Related Peptide and Bone Repair

“…CGRP mediates nociceptive transmission CGRP [25], as they act as afferent neurotransmitters after being released by sensory neurons to conduct nociception [26]. CGRP release is associated with somatic, visceral, neuropathic, and inflammatory pain [27].…”

Inhibition of Inflammatory Osteoclasts Enhances CGRP+TrkA+Signaling and Accelerates Callus Remodeling in Osteoporotic Fractures

“…Due to the lack of understanding of the mechanisms behind this healing process, an effective treatment strategy has yet to be found. Sensory nerve fibers transmit nociceptive signals, particularly evident following bone fractures (Mantyh et al, 2011;Neychev et al, 2020). Numerous studies indicate that calcitonin gene-related peptide (CGRP + ) sensory nerves have an evolutionarily conserved, crucial role in organ formation and tissue regeneration (Tomlinson et al, 2016).…”