Lack of association between angiotensin-converting enzyme inhibitors and angiotensin receptor blockers and pain improvement in patients with oral cancer

Abstract

Background: There is a growing body of literature implicating angiotensin II in the modulation of tumour-associated inflammation and pain. However, the impact of angiotensinconverting enzyme inhibitors (ACEis) and angiotensin II receptor blockers (ARBs) on pain and inflammation has not yet been studied in oral cancers. The objective is to investigate the role of ACEi and ARB pharmacotherapy on preoperative pain and inflammatory biomarkers, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and monocyte-to-lymphocyte ratio (MLR), in patients with oral cancer. Methods: We performed a retrospective study on patients who underwent oral cancer surgery. The Wilcoxon rank-sum test or Kruskal-Wallis analysis was used to evaluate differences in demographic, tumour-related and preoperative characteristics and amongst patients using ARBs, ACEis and no treatment. Multivariable analysis was fitted to estimate the effects of important covariates on severe preoperative pain. Results: A total of 162 patients with oral malignancies were included in the study. After adjusting for significant covariates, patients with perineural invasion were found to have higher levels of pain (p = 0.0278). Similarly, patients taking ARBs were found to have lower levels of perineural invasion (p = 0.035). The analysis did not demonstrate a significant difference in pain levels when comparing ARBs or ACEis to the no treatment group (p = 0.250). Furthermore, the use of ARB or ACEi did not significantly alter preoperative NLR (p = 0.701) or MLR (p = 0.869). Conclusions: When compared to no treatment, ARBs and ACEis are not associated with significant analgesic effect or decreased inflammatory scores (NLR, PLR and MLR).

Angiotensin receptors and neuropathic pain

“…These results indicate a possible mechanism for the analgesic actions of different AT1R antagonists (see section 3.3) and should be further investigated in relation to NP and other different pain diseases. AT1R antagonists are associated with reduced perineural invasion in head and neck cancer, 35 although it is not yet clear if this is due to an AT1R-mediated effect on chemokine expression. Collectively, these findings are likely to be relevant for NP because leukocyte infiltration and the consequent proinflammatory actions are known to be significant contributors to development and maintenance of NP.…”

Opioids and Cancer: Current Understanding and Clinical Considerations

“…In vitro, pancreatic adenocarcinoma cells were shown to induce neurotropism in cultured mouse dorsal root ganglion neurons, and enhanced neurite outgrowth was also associated with greater cancer cell colony growth [ 53 ]. PNI is associated with higher pain intensity [ 54 ], and pain intensity is also a predictor of poor prognosis in head and neck cancers [ 3 ] and non-small cell lung cancers [ 4 ].…”

The µ‐Opioid Receptor in Cancer and Its Role in Perineural Invasion: A Short Review and New Evidence

“…[75] One of the single most important factors of moderate-tosevere pain in patients with cancer is perineural tumor invasion. [76] This can be defined as cancer cells surrounding more than one-third of the nerve periphery or invading any layer of the neurolemma. [77] Perineural invasion is a complex and dynamic process that requires close and orchestrated interactions between axons, nerve endings, and cancer cells, and it occurs early during tumorigenesis.…”