Modern assays for assessing pain and related nociceptive and defensive actions in rodent models

Studies on pain are urgently needed to develop effective analgesic treatments with fewer adverse effects. Laboratory rodent models are invaluable tools for examining pain and its underlying neural mechanisms. However, pain is considered a subjective experience, and its assessment in animal models relies heavily on behavioral measurements evoked in animals accompanied by the presence of noxious stimuli. Two behavioral measurement metrics are employed to objectively assess pain (i.e., nociception) and the underlying neural circuits in rodent models: (1) stimulus-evoked pain reactions as a reflective response, and (2) pain-related actions as a subsequent adaptive defense response. As a derivation from these measurements, recent developments in pain assessment assays have aimed to address spontaneous pain; e.g., non-external stimulus- evoked pain-related responses by measuring motor and autonomic actions, such as facial expressions and vocalization, accompanying the experience of pain or by detecting alterations in routine behaviors and the acquisition of adaptive reactions. Although appropriate choice and accurate assessment using these pain assays promise a better understanding of pain and its neural circuitry mechanisms, the most important requirement for performing pain assessment is to clearly determine which pain circuitry processes and relevant responses need to be assessed for the intended purpose of interest. This review covers recent updates on pain assays and applications for investigating associated neural circuit functions. (215 words).