Distinct environmental enrichment protocols reduce anxiety but differentially modulate pain sensitivity in rats

Kimura, Louise F.; Mattaraia, Vânia Gomes de Moura; Picolo, Gisele

doi:10.1016/j.bbr.2017.11.012

Cited by 23 publications

(13 citation statements)

References 20 publications

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“…EE comprises animal housing conditions which provide physical exercise, cognitive stimulation, and also favor social interactions (45,46). EE can exert such effects as reduction and prevention of epileptic seizures, as well as analgesic effects in various neuropathic pain models in rats and mice (45,(47)(48)(49)(50)(51). Similarly to EE, music produces diverse physiological responses in rodents including improved memory, analgesia, antidepressant and antiseizure activities, as illustrated in Table 1.…”

Section: Introductionmentioning

confidence: 99%

Music-Enhanced Analgesia and Antiseizure Activities in Animal Models of Pain and Epilepsy: Toward Preclinical Studies Supporting Development of Digital Therapeutics and Their Combinations With Pharmaceutical Drugs

Metcalf

Huntsman

Garcia³

et al. 2019

Front. Neurol.

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Digital therapeutics (software as a medical device) and mobile health (mHealth) technologies offer a means to deliver behavioral, psychosocial, disease self-management and music-based interventions to improve therapy outcomes for chronic diseases, including pain and epilepsy. To explore new translational opportunities in developing digital therapeutics for neurological disorders, and their integration with pharmacotherapies, we examined analgesic and antiseizure effects of specific musical compositions in mouse models of pain and epilepsy. The music playlist was created based on the modular progression of Mozart compositions for which reduction of seizures and epileptiform discharges were previously reported in people with epilepsy. Our results indicated that music-treated mice exhibited significant analgesia and reduction of paw edema in the carrageenan model of inflammatory pain. Among analgesic drugs tested (ibuprofen, cannabidiol (CBD), levetiracetam, and the galanin analog NAX 5055), music intervention significantly decreased paw withdrawal latency difference in ibuprofen-treated mice and reduced paw edema in combination with CBD or NAX 5055. To the best of our knowledge, this is the first animal study on music-enhanced antinociceptive activity of analgesic drugs. In the plantar incision model of surgical pain, music-pretreated mice had significant reduction of mechanical allodynia. In the corneal kindling model of epilepsy, the cumulative seizure burden following kindling acquisition was lower in animals exposed to music. The music-treated group also exhibited significantly improved survival, warranting further research on music interventions for preventing Sudden Unexpected Death in Epilepsy (SUDEP). We propose a working Metcalf et al. Music-Enhanced Analgesic and Antiseizure Activities model of how musical elements such as rhythm, sequences, phrases and punctuation found in K.448 and K.545 may exert responses via parasympathetic nervous system and the hypothalamic-pituitary-adrenal (HPA) axis. Based on our findings, we discuss: (1) how enriched environment (EE) can serve as a preclinical surrogate for testing combinations of non-pharmacological modalities and drugs for the treatment of pain and other chronic diseases, and (2) a new paradigm for preclinical and clinical development of therapies leading to drug-device combination products for neurological disorders, depression and cancer. In summary, our present results encourage translational research on integrating non-pharmacological and pharmacological interventions for pain and epilepsy using digital therapeutics.

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Section: Introductionmentioning

confidence: 99%

Music-Enhanced Analgesia and Antiseizure Activities in Animal Models of Pain and Epilepsy: Toward Preclinical Studies Supporting Development of Digital Therapeutics and Their Combinations With Pharmaceutical Drugs

Metcalf

Huntsman

Garcia³

et al. 2019

Front. Neurol.

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“…Besides visual enrichment, EE protocols that provide a greater variety of novel objects and enlarged living space in early life can reduce allodynia and anxiety . The underlying mechanisms remain unexplored but may be related to the implementation of EE since birth.…”

Section: Ee In Animal Models Of Neuropathic Painmentioning

confidence: 99%

“…Besides visual enrichment, EE protocols that provide a greater variety of novel objects and enlarged living space in early life can reduce allodynia and anxiety. 85 The underlying mechanisms remain unexplored but may be related to the implementation of EE since birth. Early introduction of EE has been shown to produce significant neuroprotective effects and benefit nociceptive transduction, perception, and modulation.…”

Section: Experimental Studies Of Ee In Animal Models Of Peripheral Nementioning

confidence: 99%

“…44 Indeed, although mice run readily upon the provision of a wheel, voluntary running in rats can be highly variable. 97 Still, an early implementation of EE has been proven to be effective in both mice and rats, 70,85 implying that EE should be started as soon as safely possible. This is in line with the clinical theory that rehabilitation should be started as early as appropriate after acute major injuries or *Enrichment start point/duration: post, post-injury.…”

Section: Experimental Limitations and Future Perspectives In Animal Smentioning

confidence: 99%

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Enriched Environment and Effects on Neuropathic Pain: Experimental Findings and Mechanisms

2018

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Neuropathic pain inflicts tremendous biopsychosocial suffering for patients worldwide. However, safe and effective treatment of neuropathic pain is a prominent unmet clinical need. Environmental enrichment (EE) is an emerging cost-effective nonpharmacological approach to alleviate neuropathic pain and complement rehabilitation care. We present here a review of preclinical studies in ascertaining the efficacy of EE for neuropathic pain. Their proposed mechanisms, including the suppression of ascending nociceptive signaling to the brain, enhancement of the descending inhibitory system, and neuroprotection of the peripheral and central nervous systems, may collectively reduce pain perception and improve somatic and emotional functioning in neuropathic pain. The current evidence offers critical insights for future preclinical research and the translational application of EE in clinical pain management.

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“…In male Wistar rats, these complex environments have also been shown to attenuate the impairment in cognitive flexibility induced by basal forebrain lesions (De Bartolo et al, 2008), and improve spatial learning in rats with subicular lesion-induced neurodegeneration (Dhanushkodi et al, 2007). Different enriched environments can also have differential effects on pain sensitivity in rats; in particular, more complex enriched environments are associated with a more effective ability to diminish pain sensitivity (Kimura et al, 2019). However, no analogous studies comparing different types of housing environments (e.g.…”

Section: Introductionmentioning

confidence: 99%

Physical activity and environmental enrichment: Behavioural effects of exposure to different housing conditions in mice

Rabadán¹,

Ramos-Campos²,

Redolat³

et al. 2020

Acta Neurobiologiae Experimentalis

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Enriched environments and exercise provide complex environmental stimulation that can induce emotional and cognitive changes; however, few studies have evaluated the effects of these two components on other behaviours, such as novelty seeking or pain sensitivity. The aim of the present study was to investigate the influence of voluntary physical activity provided through different housing conditions on anxiety, locomotor activity, pain sensitivity, and exploration. Male mice at postnatal day (PND) 21 and were randomly assigned to one of four different conditions on PND 28: Marlau cages (MC), a standardized cage designed to provide a complex environment; physical exercise in large groups (PE-8); physical exercise in small groups (PE-4); or a standard environment (SE). After seven weeks, animals were evaluated in the hole-board task, the elevated zero maze, actimeter, and hot plate test. In the hole-board task, MC animals displayed more exploration than animals in the PE-8 and PE-4 groups, but no significant differences were observed between groups in the actimeter. In the elevated zero maze, MC and PE-8 animals exhibited an anxiogenic-like profile as compared to the SE group. When pain sensitivity was evaluated, the PE-8 group displayed a higher sensitivity to noxious thermal stimuli than the SE group. These data suggest that the complexity of the environment in which physical activity and environmental stimulation are provided can influence animal behaviours such as novelty seeking, emotional response, and pain sensitivity. These animal models could be useful for designing more personalized interventions that include physical, social, and cognitive stimulation to promote a more active lifestyle in humans. Such interventions could be useful in the prevention and treatment of aging-related decline or neurodegenerative diseases.

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Distinct environmental enrichment protocols reduce anxiety but differentially modulate pain sensitivity in rats

Cited by 23 publications

References 20 publications

Music-Enhanced Analgesia and Antiseizure Activities in Animal Models of Pain and Epilepsy: Toward Preclinical Studies Supporting Development of Digital Therapeutics and Their Combinations With Pharmaceutical Drugs

Music-Enhanced Analgesia and Antiseizure Activities in Animal Models of Pain and Epilepsy: Toward Preclinical Studies Supporting Development of Digital Therapeutics and Their Combinations With Pharmaceutical Drugs

Enriched Environment and Effects on Neuropathic Pain: Experimental Findings and Mechanisms

Physical activity and environmental enrichment: Behavioural effects of exposure to different housing conditions in mice

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