Nociceptive Tests as Part of Multimodal Pain Assessment in Preclinical Trials (Review)

INTRODUCTION. Currently, preclinical development of analgetic drugs is facing a large number of obstacles, mostly due to the limited validity of models and methods for pain assessment. To overcome the translational barrier in the development of analgetics, it is necessary to revise the existing methods for assessing pain sensitivity and develop new approaches that include both the study of reflexive and affective pain component.

AIM. This study aimed to systematize a contemporary view of pain assessment methods in laboratory animals and develop applicability criteria in preclinical trials of new analgesics.

DISCUSSION. The literature review included 75 references, among them original research and systematic reviews over the past 35 years. Pain is a multidimensional phenomenon that includes sensory, discriminatory and affective-motivational components. Standard nociceptive tests effectively evaluate sensory hypersensitivity, however, they are not sensitive enough when studying chronic pain based on an affective component. Less widely used non-reflexive methods (grimace scale, ultrasound vocalization, burrowing test) allow assessing the affective component; still, they have low specificity and are insufficiently validated for various pain models. A combined, polymodal approach enhances the objectivity, reproducibility, and translational predictivity of preclinical research towards the development of new analgetics.

CONCLUSIONS. Nociceptive tests are a tool for assessing efficacy of anesthetics both at a primary screening and in preclinical trials. Standard nociceptive tests do not allow assessing affective pain component, thus development of new anesthetics necessitates an introduction of non-reflexive pain assessment in the preclinical trials. A combination of reflexive and non-reflexive pain assessment methods is a base for new research strategies in preclinical trials.

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