Effects of Acute and Sustained Pain Manipulations on Performance in a Visual‐Signal Detection Task of Attention in Rats

Freitas, Kelen; Hillhouse, Todd M.; Leitl, Michael; Negus, S. Stevens

doi:10.1002/ddr.21255

Cited by 17 publications

(17 citation statements)

References 31 publications

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“…Several tests of pain-depressed behaviors in rodents have been developed. These include pain-depressed reductions in feeding/drinking (Kwilasz and Negus, 2012; Stevenson et al, 2006), intracranial self-stimulation (ICSS) (Negus, 2013), overall locomotor activity (Matson et al, 2007; Stevenson et al, 2009), burrowing (Andrews et al, 2012; Rutten et al, 2014), nesting (Negus et al, 2015), and attention (Freitas et al, 2015). Although these tests mimic the effects of clinical pain in many ways, they are limited by assessment of nociception over a constrained time, assessment outside the home cage, and/or difficulty quantifying the duration and magnitude of pain.…”

Section: Introductionmentioning

confidence: 99%

Home cage wheel running is an objective and clinically relevant method to assess inflammatory pain in male and female rats

Kandasamy

Calsbeek

Morgan

2016

Journal of Neuroscience Methods

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Background The assessment of nociception in preclinical studies is undergoing a transformation from pain-evoked to pain-depressed tests to more closely mimic the effects of clinical pain. Many inflammatory pain-depressed behaviors (reward seeking, locomotion) have been examined, but these tests are limited because of confounds such as stress and difficulties in quantifying behavior. New Method The present study evaluates home cage wheel running as an objective method to assess the magnitude and duration of inflammatory pain in male and female rats. Results Injection of Complete Freund’s Adjuvant (CFA) into the right hindpaw to induce inflammatory pain almost completely inhibited wheel running for 2 days in males and females. Wheel running gradually returned to baseline levels within 12 days despite persistent mechanical hypersensitivity (von Frey test). Comparison with Existing Methods Continuously monitoring home cage wheel running improves on previous studies examining inflammatory pain-depressed wheel running because it is more sensitive to noxious stimuli, avoids the stress of removing the rat from its cage for testing, and provides a complete analysis of the time course for changes in nociception. Conclusions The present data indicate that home cage wheel running is a clinically relevant method to assess inflammatory pain in the rat. The decrease in activity caused by inflammatory pain and subsequent gradual recovery mimics the changes in activity caused by pain in humans. The tendency for pain-depressed wheel running to be greater in female than male rats is consistent with the tendency for women to be at greater risk of chronic pain than men.

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Section: Introductionmentioning

confidence: 99%

Home cage wheel running is an objective and clinically relevant method to assess inflammatory pain in male and female rats

Kandasamy

Calsbeek

Morgan

2016

Journal of Neuroscience Methods

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“…Pain-depressed behaviors are defined as behaviors that decrease in rate, frequency, or intensity in response to a noxious stimulus or pain state [23]. Previous animal studies have examined pain-induced depression of feeding [17,30], intracranial self-stimulation [23], attention [12], nesting [24], and wheel running [6]. We have recently shown that home cage wheel running is an objective and sensitive method to assess the functional consequences of inflammatory pain in male and female rats [16].…”

Section: Introductionmentioning

confidence: 99%

Analysis of inflammation-induced depression of home cage wheel running in rats reveals the difference between opioid antinociception and restoration of function

Kandasamy

Calsbeek

Morgan

2017

Behavioural Brain Research

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Opioids are effective at inhibiting responses to noxious stimuli in rodents, but have limited efficacy and many side effects in chronic pain patients. One reason for this disconnect is that nociception is typically assessed using withdrawal from noxious stimuli in animals, whereas chronic pain patients suffer from abnormal pain that disrupts normal activity. We hypothesized that assessment of home cage wheel running in rats would provide a much more clinically relevant method to assess opioid efficacy to restore normal behavior. Intraplantar injection of Complete Freund’s Adjuvant (CFA) into the right hindpaw depressed wheel running and caused mechanical allodynia measured with the von Frey test in both male and female rats. Administration of an ED50 dose of morphine (3.2 mg/kg) reversed mechanical allodynia, but did not reverse CFA-induced depression of wheel running. In contrast, administration of a low dose of morphine (1.0 mg/kg) restored running for one hour in both sexes, but had no effect on mechanical allodynia. Administration of the atypical opioid buprenorphine had no effect on inflammation-induced depression of wheel running in male or female rats, but attenuated mechanical allodynia in male rats. Administration of buprenorphine and higher doses of morphine depressed wheel running in non-inflamed rats, suggesting that the side effects of opioids interfere with restoration of function. These data indicate that restoration of pain-depressed function requires antinociception in the absence of disruptive side effects. The disruptive side effects of opioids are consistent with the major limitation of opioid use in human pain patients.

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“…29 A recent study failed to find a disruptive effect of lactic acid administration on attention using a signal detection task however, except at a relatively large concentrations (3.2 and 5.6%) which increased the latency to correct responses and the number of omitted trials with no change in accuracy, similar to the effects found at a lower concentration in the present study. 35 The same range of doses of scopolamine used in the present study produced disruption in this signal detection task 35 . Induction of colitis with 2,4,6-trinitrobenzenesulfonic acid, a more chronic form of abdominal nociception, disrupts performance in a novel object recognition task in rats, however the effects of morphine in this assay were mixed with only a single dose producing a reversal of these effects 36 .…”

Section: Discussionmentioning

confidence: 62%

Assessment of Behavioral Disruption in Rats with Abdominal Inflammation Using Visual Cue Titration and the Five-choice Serial-reaction Time Task

et al. 2017

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Background Both acute and chronic pain result in a number of behavioral symptoms in patients, including cognitive effects such as decreased attention and working memory. Intraperitoneal administration of dilute lactic acid in rodents has been used to induce abdominal inflammation and produce effects in behavioral assays of both sensory-discriminative and affective pain modalities. Methods Intraperitoneal injection of dilute lactic acid was used to study the impact of abdominal inflammation on an operant task requiring sustained visual attention in rats (N = 7 to 15/group) that adapts dynamically to performance ability. The effects of ketoprofen and morphine on lactic acid–induced impairment were compared with those on the disruptive effects of scopolamine. Results Lactic acid impaired performance in a concentration-dependent manner, increasing the duration of cue presentation required to maintain optimal performance from 0.5 ± 0.2 s (mean ± SD) to 17.2 ± 11.4 s after the administration of 1.8% (v/v) (N = 13). The latency to emit correct responses and to retrieve the food reward were both increased by lactic acid. All effects of lactic acid injection were reversed by both ketoprofen and morphine in a dose-dependent manner. Scopolamine, however, produced dose-dependent, nonpain-related disruption in sustained attention that was not altered by either ketoprofen or morphine. Conclusions These data demonstrate that abdominal inflammation induced by lactic acid produces robust disruption in a visual attention-based operant task and that this disruption is reversed by analgesics. Future studies will focus on pain-related circuitry and its impact on both limbic forebrain and frontal cortical mechanisms.

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Effects of Acute and Sustained Pain Manipulations on Performance in a Visual‐Signal Detection Task of Attention in Rats

Cited by 17 publications

References 31 publications

Home cage wheel running is an objective and clinically relevant method to assess inflammatory pain in male and female rats

Home cage wheel running is an objective and clinically relevant method to assess inflammatory pain in male and female rats

Analysis of inflammation-induced depression of home cage wheel running in rats reveals the difference between opioid antinociception and restoration of function

Assessment of Behavioral Disruption in Rats with Abdominal Inflammation Using Visual Cue Titration and the Five-choice Serial-reaction Time Task

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