Associations between autonomic dysfunction and pain in chemotherapy-induced polyneuropathy

Background: Autonomic neuropathy, a relatively common complication of several chemotherapy agents, can affect the vagus nerve and its pain inhibitory capacity, thus increasing sensitivity to pain. This study aimed to evaluate the relationships between autonomic parasympathetic function and the perception of (1) spontaneous pain; (2) experimental non-painful sensations; and (3) experimental painful sensations in chemotherapy-induced neuropathy patients. Methods: Twenty-seven cancer patients with chemotherapy-induced polyneuropathy were enrolled (20 women, age 56.6 ± 7.9). Autonomic parameters of heart rate variability, deep-breathing and Valsalva ratios, experimental non-painful parameters of warm, cold and mechanical detection thresholds, and painful parameters of heat pain thresholds, pain rating of suprathreshold stimulus, mechanical temporal summation and conditioned pain modulation response were examined. Results: Autonomic parameters and spontaneous pain levels were not associated, yet autonomic parameters were positively correlated with nonpainful sensations - milder autonomic neuropathy was accompanied by milder sensory neuropathy as indicated by several parameters, e.g., lower Valsalva ratio was correlated with higher warmth detection threshold (r = -0.465; p = 0.033). Autonomic parameters were, however, negatively correlated with painful sensations - lower parasympathetic-vagal activity was associated with higher pain sensitivity as indicated by several parameters, e.g., lower Valsalva ratio was correlated with higher pain rating of suprathreshold stimulus (r = -0.559; p = 0.008). Conclusions: Diminished vagal function due to neuropathy is associated with, and may possibly underlie, pain disinhibition expressed as greater levels of experimental pain.