Measuring Pain Avoidance‐Like Behavior in Drug‐Dependent Rats

Pahng, Amanda R.; Edwards, Scott

doi:10.1002/cpns.53

Cited by 13 publications

(9 citation statements)

References 34 publications

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“…Mechanical allodynia is a robust method for measuring hyperalgesia during nicotine withdrawal (Carstens, Anderson et al 2001, Cohen, Treweek et al 2015, Hamouda, Jackson et al 2018, Pahng and Edwards 2018, Xue, Kallupi et al 2018). In the present study, a reduction of hyperalgesia was observed at all the doses of CBD tested during acute withdrawal and protracted abstinence.…”

Section: Discussionmentioning

confidence: 99%

Cannabidiol reduces withdrawal symptoms in nicotine-dependent rats

et al. 2021

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Rationale: Cannabidiol (CBD) reduces craving in animal models of alcohol and cocaine seeking and is known to modulate nicotinic receptor function, suggesting that it may alleviate symptoms of nicotine withdrawal; however, preclinical evaluation of its efficacy is still lacking. Objectives:The goal of this study was to test the preclinical efficacy of a chronic CBD treatment in reducing nicotine dependence using measures of withdrawal symptoms including somatic signs, hyperalgesia, and weight gain during acute and protracted abstinence.Methods: Male and female Wistar rats were made dependent on nicotine using osmotic minipumps (3.15 mg/kg/day) for two weeks, after which minipumps were removed to induce spontaneous withdrawal. Three groups received CBD injections at doses of 7.5, 15, and 30 mg/kg/day for two weeks, starting one week into chronic nicotine infusion. The control groups included rats with nicotine minipumps that received vehicle injections of sesame oil instead of CBD; rats implanted with saline minipumps that received sesame oil injections (double vehicle) or the highest dose of CBD 30mg/kg/day. Throughout the experiment, serum was collected for determination of CBD and nicotine concentrations, mechanical sensitivity threshold and withdrawal scores were measured, and body weight was recorded.Results: CBD prevented rats from exhibiting somatic signs of withdrawal and hyperalgesia during acute and protracted abstinence. There was no dose-response observed for CBD, suggesting a ceiling effect at the doses used and the potential for lower effective doses of CBD.The saline minipump group did not show either somatic signs of withdrawal or hyperalgesia during acute and protracted abstinence, and the highest dose of CBD used (30mg/kg/day) did not alter these results. 3Conclusions: This preclinical study suggests that using CBD as a strategy to alleviate the withdrawal symptoms upon nicotine-cessation may be beneficial.

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Section: Discussionmentioning

confidence: 99%

Cannabidiol reduces withdrawal symptoms in nicotine-dependent rats

et al. 2021

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“…The tail‐flick and hot‐plate tests are most commonly used to evaluate the analgesic efficacy of drugs, whereas the Hargreaves and von Frey tests are used to evaluate both analgesia and pain‐like states (hyperalgesia/allodynia). However, based on the considerable lack of translational efficacy of putative analgesics as examined via these preclinical methods, many researchers are now transitioning away from reflex‐based assays toward more cognitive and motivational tasks that are thought to be more related to the negative affective components of pain (e.g., Pahng and Edwards, ; Tappe‐Theodor et al, ).…”

Section: Preclinical Models To Investigate the Intersection Of Aud Anmentioning

confidence: 99%

“…Finally, as mentioned above the motivational and affective components of pain have started to be more thoroughly investigated in rodent models. A potential model for this purpose was recently described by Pahng and Edwards (). This model incorporates a non–reflex‐based method to measure pain avoidance‐like behavior in rats.…”

Section: Preclinical Models To Investigate the Intersection Of Aud Anmentioning

confidence: 99%

Alcohol and Pain: A Translational Review of Preclinical and Clinical Findings to Inform Future Treatment Strategies

Edwards

Vendruscolo

Gilpin

et al. 2020

Alcoholism Clin & Exp Res

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Alcohol use disorder (AUD) and chronic pain are enduring and devastating conditions that share an intersecting epidemiology and neurobiology. Chronic alcohol use itself can produce a characteristic painful neuropathy, while the regular analgesic use of alcohol in the context of nociceptive sensitization and heightened affective pain sensitivity may promote negative reinforcement mechanisms that underlie AUD maintenance and progression. The goal of this review was to provide a broad translational framework that communicates research findings spanning preclinical and clinical studies, including a review of genetic, molecular, behavioral, and social mechanisms that facilitate interactions between persistent pain and alcohol use. We also consider recent evidence that will shape future investigations into novel treatment mechanisms for pain in individuals suffering from AUD.

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“…These non-reflexive-based assays allow the potential to examine the contribution of negative affective-like states towards activity avoidance and pain interference in the context of SUD. 47 , 48 In the mechanical conflict-avoidance system (MCS) task, animals traverse mechanically noxious probes of varying heights to avoid a bright aversive light, escaping to reach a goal chamber that is dark. A longer latency to exit onto the probes reflects increased pain avoidance-like behavior as a motivational correlate of hyperalgesia.…”

Section: Animal Models To Examine Pain and Sud Interactionsmentioning

confidence: 99%

“…The specific strengths and limitations of the MCS procedure have been described, illustrating its utility in measuring both analgesic and hyperalgesic conditions. 47 , 49 , 50 Another innovative technique in this area is the Orofacial Pain Assessment Device (OPAD), which pairs a thermal stimulus conflict with access to an appetitive reward 51 and can be readily applied to oral alcohol or opioid self-administration. These reflex-based and non-reflex-based pain assays can be used in tandem to more comprehensively examine the effects of opioid and alcohol dependence on both somatic and affective pain-like behaviors in rodents.…”

Section: Animal Models To Examine Pain and Sud Interactionsmentioning

confidence: 99%

The Convergent Neuroscience of Affective Pain and Substance Use Disorder

Pahng

Edwards

2021

ARCR

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Opioids and alcohol are widely used to relieve pain, with their analgesic efficacy stemming from rapid actions on both spinal and supraspinal nociceptive centers. As an extension of these relationships, both substances can be misused in attempts to manage negative affective symptoms stemming from chronic pain. Moreover, excessive use of opioids or alcohol facilitates the development of substance use disorder (SUD) as well as hyperalgesia, or enhanced pain sensitivity. Shared neurobiological mechanisms that promote hyperalgesia development in the context of SUD represent viable candidates for therapeutic intervention, with the ideal strategy capable of reducing both excessive substance use as well as pain symptoms simultaneously. Neurocognitive symptoms associated with SUD, ranging from poor risk management to the affective dimension of pain, are likely mediated by altered activities of key anatomical elements that modulate executive and interoceptive functions, including contributions from key frontocortical regions. To aid future discoveries, novel and translationally valid animal models of chronic pain and SUD remain under intense development and continued refinement. With these tools, future research strategies targeting severe SUD should focus on the common neurobiology between negative reinforcement and affective elements of pain, possibly by reducing excessive stress hormone and neurotransmitter activity within shared circuitry.

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Measuring Pain Avoidance‐Like Behavior in Drug‐Dependent Rats

Cited by 13 publications

References 34 publications

Cannabidiol reduces withdrawal symptoms in nicotine-dependent rats

Cannabidiol reduces withdrawal symptoms in nicotine-dependent rats

Alcohol and Pain: A Translational Review of Preclinical and Clinical Findings to Inform Future Treatment Strategies

The Convergent Neuroscience of Affective Pain and Substance Use Disorder

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