Behavioral tests of pain phenotype

In addition to new models, work is being conducted to improve the range of behavioral tests employed in vivo (Figure 1.3). For example, spontaneous exploratory activity assessed in the open field paradigm is classically used as a measure of anxiety-related behavior in rodents.28 This test has been used as a measure of locomotor activity in pain models29 and more recently, additional measures of thigmotactic behavior indicate the presence of altered exploratory behavior in rodent models of pain without the presence of locomotor deficits. This behavior is sensitive to clinically employed analgesics, such as gabapentin and morphine,19,27 suggesting the thigmotaxis to be correlated to a nonstimulus-evoked pain-like behavior in rodents be it spontaneous pain or pain comorbidities.

Figure 1.3 Examples of behavioral paradigms adapted for the assessment of pain conditions in rodents. (a-c) The open field paradigm in which neuropathic rats display thigmotactic (wall hugging) behavior: (a) open field arena; (b) naive rat; (c) rat with nerve injury. (d) The dark/light box: place preference paradigm in which rats chose between the aversive noxious stimulus or the aversive light compartment.

Figure 1.3 Examples of behavioral paradigms adapted for the assessment of pain conditions in rodents. (a-c) The open field paradigm in which neuropathic rats display thigmotactic (wall hugging) behavior: (a) open field arena; (b) naive rat; (c) rat with nerve injury. (d) The dark/light box: place preference paradigm in which rats chose between the aversive noxious stimulus or the aversive light compartment.

Further types of test involve active escape and avoidance of preferred environments (such as a dark versus light arena) in association with noxious stimuli.30 These tests involve conflicting choices in which the animal must choose an adverse environment over the presence of a noxious stimulus and appear to respond well to analgesic drugs.31 Alternatively, place preference paradigms associate a place with a preferable treatment such as delivery of an analgesic drug. However, the development of the latter paradigm in relation to neuropathic pain is ongoing and their utility remains to be proven. It is important to remember the effects of species variability32 and therefore care must be taken to establish the suitability of tests in rodents.

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