Studying ongoing and spontaneous pain in rodents – challenges and opportunities

Abstract

The measurement of spontaneous ongoing pain in rodents is a multiplex issue and a subject of extensive and longstanding debate. Considering the need to align available rodent models with clinically relevant forms of pain, it is of prime importance to thoroughly characterize behavioral outcomes in rodents using a portfolio of measurements that are not only stimulus-dependent but also encompass voluntary behavior in unrestrained animals. Moreover, the temporal course and duration of behavioral tests should be taken into consideration when we plan our studies to measure explicit chronic pain, with a particular emphasis on performing longitudinal studies in rodents. While using rodents as model organisms, it is also worth considering their circadian rhythm and the influence of the test conditions on the behavioral results, which are affected by social paradigms, stress and anxiety. In humans, general wellbeing is closely related to pain perception, which also makes it necessary in rodents to consider modulators as well as readouts of overall wellbeing. Optimizing the above parameters in study design and the new developments that are forthcoming to test the affective motivational components of pain hold promise in solving inconsistencies across studies and improving their broad applicability in translational research. In this review, we critically discuss a variety of behavioral tests that have been developed and reported in recent years, attempt to weigh their benefits and potential limitations, and discuss key requirements and challenges that lie ahead in measuring ongoing pain in rodent models.

Role of Prelimbic GABAergic Circuits in Sensory and Emotional Aspects of Neuropathic Pain

“…Second, optogenetic stimulation and inhibition of PVINs not only altered CPP scores but also affected sensory pain behavior in SNI animals. A distinction between effects on emotional aspects of pain and learning and memory is a challenge with currently available paradigms for measuring emotional pain (Tappe-Theodor and Kuner, 2014). To address this issue, we used a place escape/avoidance (PEA) paradigm as an additional measure of emotional aspects of pain processing (LaBuda and Fuchs, 2000;LaGraize and Fuchs, 2007).…”

Nerve injury induced activation of fast-conducting high threshold mechanoreceptors predicts non-reflexive pain related behavior

“…Spontaneous, or non-reflexive, measures of pain likely provide different information about the nociceptive input and its impact to the whole animal, more along the lines of the subjective description of actual pain [14,15]. However, some types of non-reflexive or spontaneous pain behaviors in the animal may still rely predominantly on a reflexive pathway in the spinal cord.…”

Looking beyond the intervertebral disc: the need for behavioral assays in models of discogenic pain

“…Spontaneous pain, sometimes referred to as clinical pain, is seen in chronic pain disorders. 58 It is not stimulus-dependent, and in animal studies spontaneous pain is described as voluntary behavior and can be measured by assessing the behaviors of animals in unrestrained condition 59 . Unlike spontaneous pain, evoked pain is stimulus dependent and can be measured across different sensory modalities, including mechanical and thermal stimuli.…”

“…Evoked pain measurements are often used to assess changes in pain thresholds in animal studies and to diagnose human pathology. 59 For patients presenting with LBP, evoked pain tests, such as the straight leg raise, or provocative discography are commonly used to determine if the pain is discogenic in origin. 60,61 …”