Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers Modulate the Function of Myelinated Fibers after Chemotherapy: A Quantitative Sensory Testing Study

Abstract

Background: Angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) have sufficient scientific support for their use as tissue protectors. Preliminary studies suggest that their angiotensin-II type 2 receptor (AT2R)-blocking properties have a beneficial profile in the treatment of neuropathic pain. Objectives: The purpose of the current study was to quantify the extent of the somatosensory effects of ACEI and ARB in cancer patients with chemotherapy-induced peripheral neuropathy. Study Design: We performed a retrospective review of cancer patients with peripheral neuropathy of the upper limbs induced by known neurotoxic anti-cancer agents. Setting: Pain Medicine department at academic tertiary care cancer center. Methods: Using our quantitative sensory testing (QST) data bank, we retrospectively compared the tactile function and the touch, sharp, and thermal thresholds of patients who were previously receiving ACEI or ARB for high blood pressure with these variables in controls who were not receiving ACEI or ARB. Results: Of the 209 patients available for analysis, 145 met inclusion criteria. Baseline characteristics of patients included were generally similar. We identified 29 patients who were receiving AT2R inhibitors prior to starting chemotherapy. Touch thresholds were statistically lower in the thenar aspect of hand in the study group (patients who received AT2R inhibitors) than in the control group [mean (± SD), median 3.03 g (± 11.05), median 0.56 g and 6.75 g (± 18.28), 0.56 g, respectively (P = 0.0441)]. Similarly, the cold pain threshold was statistically higher at the thenar area for the study group [mean (± SD), median 13.23°C (± 8.02), 11.73°C] than for controls [9.89°C (± 6.62), 10.05°C (P = 0.0369)]. Limitations: Inadequacies in the original data acquisition and documentation of the QST and the medical records could not be addressed due to the retrospective nature of the study. Similarly, a discrepancy on the size of the comparison groups could not be reconciled. In addition, based on the available information and the lack of documented concomitant pain levels, we did not find an objective parameter able to correlate the QST findings with pain levels. Conclusions: AT2R inhibitors might offer partial and selective neuroprotective qualities of the myelinated fibers A-β and A-δ in cancer patients who receive neurotoxic chemotherapy. Key words: Quantitative sensory testing, chemotherapy-induced peripheral neuropathy, angiotensin-II type 2 receptor (AT2R)