The Study of Pain in Rats and Mice

Larson, Christina M.; Wilcox, George L.; Fairbanks, Carolyn A.

doi:10.30802/aalas-cm-19-000062

Cited by 34 publications

(23 citation statements)

References 178 publications

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“…Mice and rats are prey species and when distressed they will mask their spontaneous behavior, sensations and signs of pain. There are many factors that can influence and confound behavioral tests, for instance, aggression (males are prone to aggression) [155], gender of the experimenter (exposure to male experimenters causes in mice stress that results in stress-induced analgesia) [156], anxiety and/or agitation (caused by over-handling or repeated testing) [153] and health states like kidney injury and visceral pain. We have explained that cisplatin causes pica and dose related injuries and inflammation along the gastrointestinal tract, all of which result in visceral pain.…”

Section: Behavioral Tests and Their Weaknessmentioning

confidence: 99%

Cisplatin Mouse Models: Treatment, Toxicity and Translatability

Perše

2021

Biomedicines

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Cisplatin is one of the most widely used chemotherapeutic drugs in the treatment of a wide range of pediatric and adult malignances. However, it has various side effects which limit its use. Cisplatin mouse models are widely used in studies investigating cisplatin therapeutic and toxic effects. However, despite numerous promising results, no significant improvement in treatment outcome has been achieved in humans. There are many drawbacks in the currently used cisplatin protocols in mice. In the paper, the most characterized cisplatin protocols are summarized together with weaknesses that need to be improved in future studies, including hydration and supportive care. As demonstrated, mice respond to cisplatin treatment in similar ways to humans. The paper thus aims to illustrate the complexity of cisplatin side effects (nephrotoxicity, gastrointestinal toxicity, neurotoxicity, ototoxicity and myelotoxicity) and the interconnectedness and interdependence of pathomechanisms among tissues and organs in a dose- and time-dependent manner. The paper offers knowledge that can help design future studies more efficiently and interpret study outcomes more critically. If we want to understand molecular mechanisms and find therapeutic agents that would have a potential benefit in clinics, we need to change our approach and start to treat animals as patients and not as tools.

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Section: Behavioral Tests and Their Weaknessmentioning

confidence: 99%

Cisplatin Mouse Models: Treatment, Toxicity and Translatability

Perše

2021

Biomedicines

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“…Acute is generally mediated by Aδ fibers in response to harmful stimuli, while chronic is mediated by C-fibers and is generally thought of as pathologic since it occurs past healing ( Austin and Moalem-Taylor, 2010 ). Other pain classifications exist such as nociplastic pain sensation, which is associated with changes in the nervous system that lead to the processing of pain without tissue injury, and disease specific pain sensation such as radicular pain, which is pain sensation associated specifically with lumbar or nerve root pain ( Murphy et al, 2009 ; Larson et al, 2019 ). To note, this is not an exhaustive list of the diverse types of pain, but touches upon the most commonly described in the literature.…”

Section: Peripheral Neuropathy and Neuropathic Painmentioning

confidence: 99%

HDAC6: A Key Link Between Mitochondria and Development of Peripheral Neuropathy

English

Barton

2021

Front. Mol. Neurosci.

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Peripheral neuropathy, which is the result of nerve damage from lesions or disease, continues to be a major health concern due to the common manifestation of neuropathic pain. Most investigations into the development of peripheral neuropathy focus on key players such as voltage-gated ion channels or glutamate receptors. However, emerging evidence points to mitochondrial dysfunction as a major player in the development of peripheral neuropathy and resulting neuropathic pain. Mitochondrial dysfunction in neuropathy includes altered mitochondrial transport, mitochondrial metabolism, as well as mitochondrial dynamics. The mechanisms that lead to mitochondrial dysfunction in peripheral neuropathy are poorly understood, however, the Class IIb histone deacetylase (HDAC6), may play an important role in the process. HDAC6 is a key regulator in multiple mechanisms of mitochondrial dynamics and may contribute to mitochondrial dysregulation in peripheral neuropathy. Accumulating evidence shows that HDAC6 inhibition is strongly associated with alleviating peripheral neuropathy and neuropathic pain, as well as mitochondrial dysfunction, in in vivo and in vitro models of peripheral neuropathy. Thus, HDAC6 inhibitors are being investigated as potential therapies for multiple peripheral neuropathic disorders. Here, we review emerging studies and integrate recent advances in understanding the unique connection between peripheral neuropathy and mitochondrial dysfunction through HDAC6-mediated interactions.

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“…This takes place through Aδ fibers that are related to the sensation of localized, acute pain, and is accompanied by the avoidance reflex [ 40 , 41 ]. Electrophysiological studies classify these neurons in two main types: Type 1, HTM: High threshold mechanical nociceptors, that respond to stimuli with an elevated threshold (e.g., 50°C); and type 2, which have a lower heat threshold, but maintain an elevated threshold towards mechanical stimuli [ 42 , 43 ]. The information carried by the latter moves more slowly because it is transmitted through the activity of C fibers, which give a persistent, but poorly located, sensation that is called burning pain [ 27 ].…”

Section: Neurophysiological Pathway Of Painmentioning

confidence: 99%

Nociceptive pain and anxiety in equines: Physiological and behavioral alterations

et al. 2021

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Pain and anxiety are two of the most important concerns in clinical veterinary medicine because they arise as consequences of multiple factors that can severely affect animal welfare. The aim of the present review was to provide a description and interpretation of the physiological and behavioral alterations associated with pain and anxiety in equines. To this end, we conducted an extensive review of diverse sources on the topic. The article begins by describing the neurophysiological pathway of pain, followed by a discussion of the importance of the limbic system in responses to pain and anxiety, since prolonged exposure to situations that cause stress and pain generates such physiological changes as tachycardia, tachypnea, hypertension, hyperthermia, and heart rate variability (HRV), often accompanied by altered emotional states, deficient rest, and even aggressiveness. In the long term, animals may show deficiencies in their ability to deal with changes in the environment due to alterations in the functioning of their immune, nervous, and endocrinologic systems. In conclusion, pain and anxiety directly impact the homeostasis of organisms, so it is necessary to conduct objective evaluations of both sensations using behavioral scales, like the horse grimace scale, complemented by assessments of blood biomarkers to analyze their correlation with physiological parameters: Heart rate, respiratory rate, HRV, the parasympathetic tone activity index, lactate and glucose levels, and temperature. Additional tools – infrared thermography, for example – can also be used in these efforts to improve the quality of life and welfare of horses.

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The Study of Pain in Rats and Mice

Cited by 34 publications

References 178 publications

Cisplatin Mouse Models: Treatment, Toxicity and Translatability

Cisplatin Mouse Models: Treatment, Toxicity and Translatability

HDAC6: A Key Link Between Mitochondria and Development of Peripheral Neuropathy

Nociceptive pain and anxiety in equines: Physiological and behavioral alterations

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