Calcitonin gene-related peptide polymorphism linked to pain perception and opioid use after major abdominal surgery

Interindividual heterogeneity in postoperative pain intensity is a significant barrier in providing adequate postoperative analgesia. The intricate interactions of genetic, environmental, and social variables have been implicated in this heterogeneity. An increasing body of research indicates that hereditary variables play a significant role in pain sensitivity and the likelihood of developing chronic pain after surgery. The goal of the current research was to evaluate the impact of various CGRP genotypes on postoperative pain after major abdominal surgery.

A total of 85 individuals had general anaesthesia for major abdominal surgery. Epidural fentanyl and intravenous paracetamol were used for postoperative analgesia. The CGRP 4218T/C genotype was examined, and the relationship between the patient's genotype and the total amount of fentanyl consumed in the first 24 hours after surgery was evaluated. Additionally investigated were the relationships between various genotypes, the intensity of postoperative pain, and the adverse effects of opioids.

52.9% of the T/T genotype (wild homozygote), 35.3% of the T/C genotype (heterozygote), and 11.8% of the C/C genotype (mutant homozygote) were found in the research population. The C/C group had the greatest mean (standard deviation) total fentanyl intake in the first 24 hours (212.0 [7.5] μg), followed by the T/T group (182.8 [9.9] μg), and the T/C group had the lowest (159.6 [7.5] μg). For every research period, the C/C group reported greater pain ratings. No discernible variation was seen in the adverse effects of opioids, including nausea, vomiting, and sedation, amongst the various genotypes of CGRP 4218T/C.

The current investigation showed that the CGRP4218T/C polymorphism in the Indian population was linked to varying postoperative fentanyl usage after major abdominal operations. Twenty-four hours following surgery, the C/C group's mean fentanyl intake was significantly greater than that of the T/T and T/C genotypes. The body produces CGRP in large quantities, and it is widely known to function as a pronociceptive and proinflammatory neurotransmitter. In reaction to unpleasant stimuli, the spinal cord's dorsal horn releases it. It increases the release of substance P and a few other transmitters. Opioid drugs block the release of these neurotransmitters by acting on the presynaptic terminals of afferent nociceptors. It is conceivable that polymorphism in CGRP 4218 T/C causes these nociceptor transmitters to express themselves differently in the pain signalling pathway, which in turn affects how severe pain is. Nevertheless, there is no correlation between the CGRP4218T/C polymorphism and the unfavourable effects of opioid analgesic drugs.

Reference –

Prashant, HT; Saxena, Kirti N.; Kapoor, Seema1; Wadhwa, Bharti; Kerai, Sukhyanti; Gaba, Prachi. Correlation of pain perception and fentanyl consumption after major abdominal surgery with CGRP 4218T/C polymorphism: A prospective interventional study. Indian Journal of Anaesthesia 67(9):p 796-801, September 2023. | DOI: 10.4103/ija.ija_1033_22