Thus, monitoring the state of anti-nociception with objective, non-clinical methods is still in a state of testing and development, without well-documented and proven methods for consistent 'no-fuss' clinical daily use. Some methods, like those using systolic blood pressure, are based on the reduced sympathetic response from the Central Nervous System (CNS) when in a state of drug-induced anti-nociception during concomitant surgical stress. These include the pulse plethysmogram amplitude, heart rate variability and/or amplitude, pupillometry, muscle tonus and skin conductance.They all have limitations in interpretation, as the state of sympathetic tone is strongly influenced by numerous factors, including hypovolemia, vasopressors, atropine and patient positioning. In addition, sympathetic tone is very unspecific in the awake or lightly sedated patient, as mood and subjective feelings have a strong impact.