scholarly journals The influence of rat strain on the development of neuropathic pain and comorbid anxio-depressive behaviour after nerve injury

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Sara Hestehave ◽  
Klas S. P. Abelson ◽  
Tina Brønnum Pedersen ◽  
David P. Finn ◽  
Daniel R. Andersson ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Nerve Injury ◽  
Opioid Receptor ◽  
Stress Reactivity ◽  
Clinical Manifestations ◽  
Preference Test ◽  
Receptor Expression ◽  
Sucrose Preference Test ◽  
Inbred Rat ◽  
Functional Gait

AbstractBack-translating the clinical manifestations of human disease burden into animal models is increasingly recognized as an important facet of preclinical drug discovery. We hypothesized that inbred rat strains possessing stress hyper-reactive-, depressive- or anxiety-like phenotypes may possess more translational value than common outbred strains for modeling neuropathic pain. Rats (inbred: LEW, WKY, F344/ICO and F344/DU, outbred: Crl:SD) were exposed to Spared Nerve Injury (SNI) and evaluated routinely for 6 months on behaviours related to pain (von Frey stimulation and CatWalk-gait analysis), anxiety (elevated plus maze, EPM) and depression (sucrose preference test, SPT). Markers of stress reactivity together with spinal/brain opioid receptor expression were also measured. All strains variously developed mechanical allodynia after SNI with the exception of stress-hyporesponsive LEW rats, despite all strains displaying similar functional gait-deficits after injury. However, affective changes reflective of anxiety- and depressive-like behaviour were only observed for F344/DU in the EPM, and for Crl:SD in SPT. Although differences in stress reactivity and opioid receptor expression occurred, overall they were relatively unaffected by SNI. Thus, anxio-depressive behaviours did not develop in all strains after nerve injury, and correlated only modestly with degree of pain sensitivity or with genetic predisposition to stress and/or affective disturbances.

scholarly journals A Single Subanesthetic Dose of Ketamine Relieves Depression-like Behaviors Induced by Neuropathic Pain in Rats

2011 ◽  
Vol 115 (4) ◽  
pp. 812-821 ◽  
Author(s):  
Jing Wang ◽  
Yossef Goffer ◽  
Duo Xu ◽  
David S. Tukey ◽  
D. B. Shamir ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Nerve Injury ◽  
Forced Swim Test ◽  
Preference Test ◽  
Sucrose Preference ◽  
Spared Nerve Injury ◽  
Chronic Neuropathic Pain ◽  
Swim Test ◽  
Forced Swim ◽  
Sucrose Preference Test

Background Chronic pain is associated with depression. In rodents, pain is often assessed by sensory hypersensitivity, which does not sufficiently measure affective responses. Low-dose ketamine has been used to treat both pain and depression, but it is not clear whether ketamine can relieve depression associated with chronic pain and whether this antidepressant effect depends on its antinociceptive properties. Methods The authors examined whether the spared nerve injury model of neuropathic pain induces depressive behavior in rats, using sucrose preference test and forced swim test, and tested whether a subanesthetic dose of ketamine treats spared nerve injury-induced depression. Results Spared nerve injury-treated rats, compared with control rats, showed decreased sucrose preference (0.719 ± 0.068 (mean ± SEM) vs. 0.946 ± 0.010) and enhanced immobility in the forced swim test (107.3 ± 14.6s vs. 56.2 ± 12.5s). Further, sham-operated rats demonstrated depressive behaviors in the acute postoperative period (0.790 ± 0.062 on postoperative day 2). A single subanesthetic dose of ketamine (10 mg/kg) did not alter spared nerve injury-induced hypersensitivity; however, it treated spared nerve injury-associated depression-like behaviors (0.896 ± 0.020 for ketamine vs. 0.663 ± 0.080 for control rats 1 day after administration; 0.858 ± 0.017 for ketamine vs. 0.683 ± 0.077 for control rats 5 days after administration). Conclusions Chronic neuropathic pain leads to depression-like behaviors. The postoperative period also confers vulnerability to depression, possibly due to acute pain. Sucrose preference test and forced swim test may be used to compliment sensory tests for assessment of pain in animal studies. Low-dose ketamine can treat depression-like behaviors induced by chronic neuropathic pain.

Neuropathic pain models in the development of analgesic drugs

2011 ◽  
Vol 2 (4) ◽  
pp. 172-177 ◽  
Author(s):  
Per Hartvig Honoré ◽  
Anna Basnet ◽  
Laila Eljaja ◽  
Pernille Kristensen ◽  
Lene Munkholm Andersen ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Animal Models ◽  
Nerve Injury ◽  
Clinical Manifestations ◽  
Pharmacological Intervention ◽  
Special Focus ◽  
Surgical Performance ◽  
Neuropathic Pain Syndrome ◽  
Pain Models ◽  
Rats And Mice

AbstractIntroductionAnimal disease models are predictive for signs seen in disease. They may rarely mimic all signs in a specific disease in humans with respect to etiology, cause or development. Several models have been developed for different pain states and the alteration of behavior has been interpreted as a response to external stimulus or expression of pain or discomfort. Considerable attention must be paid not to interpret other effects such as somnolence or motor impairment as a pain response and similarly not to misinterpret the response of analgesics.Neuropathic pain is caused by injury or disease of the somatosensory system. The clinical manifestations of neuropathic pain vary including both stimulus-evoked and non-stimulus evoked (spontaneous) symptoms. By pharmacological intervention, the threshold for allodynia and hyperalgesia in the various pain modalities can be modulated and measured in animals and humans. Animal models have been found most valuable in studies on neuropathic pain and its treatment.Aim of the studyWith these interpretation problems in mind, the present text aims to describe the most frequently used animal models of neuropathic pain induced by mechanical nerve injury.MethodsThe technical surgical performance of these models is described as well as pain behavior based on the authors own experience and from a literature survey.ResultsNerve injury in the hind limb of rats and mice is frequently used in neuropathic pain models and the different types of lesion may afford difference in the spread and quality of the pain provoked. The most frequently used models are presented, with special focus on the spared nerve injury (SNI) and the spinal nerve ligation/transection (SNL/SNT) models, which are extensively used and validated in rats and mice. Measures of mechanical and thermal hypersensitivity with von Frey filaments and Hargreaves test, respectively, are described and shown in figures.ConclusionsA number of animal models have been developed and described for neuropathic pain showing predictive value in parallel for both humans and animals. On the other hand, there are still large knowledge gaps in the pathophysiologic mechanisms for the development, maintenance and progression of the neuropathic pain syndromeImplicationsBetter understanding of pathogenic mechanisms of neuropathic pain in animal models may support the search for new treatment paradigms in patients with complex neuropathic pain conditions

scholarly journals Peripherally acting mu-opioid receptor agonist attenuates neuropathic pain in rats after L5 spinal nerve injury

Pain ◽  
2008 ◽  
Vol 138 (2) ◽  
pp. 318-329 ◽  
Author(s):  
Yun Guan ◽  
Lisa M. Johanek ◽  
Timothy V. Hartke ◽  
Beom Shim ◽  
Yuan-Xiang Tao ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Nerve Injury ◽  
Opioid Receptor ◽  
Receptor Agonist ◽  
Mu Opioid Receptor ◽  
Spinal Nerve ◽  
Mu Opioid ◽  
Opioid Receptor Agonist

scholarly journals The Occurrence of Pain-Induced Depression Is Different between Rat Models of Inflammatory and Neuropathic Pain

2021 ◽  
Vol 10 (17) ◽  
pp. 4016
Author(s):  
Yung-Chi Hsu ◽  
Kuo-Hsing Ma ◽  
Shu-Lin Guo ◽  
Bo-Feng Lin ◽  
Chien-Sung Tsai ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Early Stage ◽  
Preference Test ◽  
Time Frame ◽  
Brain Regions ◽  
Rat Models ◽  
Positron Emission ◽  
Initial Injury ◽  
Sucrose Preference Test ◽  
The Brain

Various pain conditions may be associated with depressed mood. However, the effect of inflammatory or neuropathic pain on depression-like behavior and its associated time frame has not been well established in rat models. This frontward study investigated the differences in pain behavior, depression-like behavior, and serotonin transporter (SERT) distribution in the brain between rats subjected to spared nerve injury (SNI)-induced neuropathic pain or complete Freund’s adjuvant (CFA)-induced inflammatory pain. A dynamic plantar aesthesiometer and an acetone spray test were used to evaluate mechanical and cold allodynia responses, and depression-like behavior was examined using a forced swimming test and sucrose preference test. We also investigated SERT expression by using positron emission tomography. We found that the inflammation-induced pain was less severe than neuropathic pain from days 3 to 28 after induced pain; however, the CFA-injected rats exhibited more noticeable depression-like behavior and had significantly reduced SERT expression in the brain regions (thalamus and striatum) at an early stage (on days 14, 21, and 28 in two groups of CFA-injected rats versus day 28 in SNI rats). We speculated that not only the pain response after initial injury but also the subsequent neuroinflammation may have been the crucial factors influencing depression-like behavior in rats.

scholarly journals The Neuropeptide Cortistatin Alleviates Neuropathic Pain in Experimental Models of Peripheral Nerve Injury

Pharmaceutics ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 947
Author(s):  
Clara P. Falo ◽  
Raquel Benitez ◽  
Marta Caro ◽  
Maria Morell ◽  
Irene Forte-Lago ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Peripheral Nerve ◽  
Nerve Injury ◽  
Peripheral Nerve Injury ◽  
Clinical Manifestations ◽  
Somatosensory System ◽  
Experimental Models ◽  
Protective Capacity ◽  
Chronic Neuropathic Pain ◽  
Inflammatory Conditions

Neuropathic pain is one of the most severe forms of chronic pain caused by the direct injury of the somatosensory system. The current drugs for treating neuropathies have limited efficacies or show important side effects, and the development of analgesics with novel modes of action is critical. The identification of endogenous anti-nociceptive factors has emerged as an attractive strategy for designing new pharmacological approaches to treat neuropathic pain. Cortistatin is a neuropeptide with potent anti-inflammatory activity, recently identified as a natural analgesic peptide in several models of pain evoked by inflammatory conditions. Here, we investigated the potential analgesic effect of cortistatin in neuropathic pain using a variety of experimental models of peripheral nerve injury caused by chronic constriction or partial transection of the sciatic nerve or by diabetic neuropathy. We found that the peripheral and central injection of cortistatin ameliorated hyperalgesia and allodynia, two of the dominant clinical manifestations of chronic neuropathic pain. Cortistatin-induced analgesia was multitargeted, as it regulated the nerve damage-induced hypersensitization of primary nociceptors, inhibited neuroinflammatory responses, and enhanced the production of neurotrophic factors both at the peripheral and central levels. We also demonstrated the neuroregenerative/protective capacity of cortistatin in a model of severe peripheral nerve transection. Interestingly, the nociceptive system responded to nerve injury by secreting cortistatin, and a deficiency in cortistatin exacerbated the neuropathic pain responses and peripheral nerve dysfunction. Therefore, cortistatin-based therapies emerge as attractive alternatives for treating chronic neuropathic pain of different etiologies.

scholarly journals Naked mole-rats lack cold sensitivity before and after nerve injury

2020 ◽  
Vol 16 ◽  
pp. 174480692095510
Author(s):  
Sandra J Poulson ◽  
Ahmed Aldarraji ◽  
Iqra I Arain ◽  
Natalia Dziekonski ◽  
Keza Motlana ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Nerve Injury ◽  
Messenger Rna ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Receptor Expression ◽  
Mustard Oil ◽  
Cold Sensitivity ◽  
Mechanical Stimuli ◽  
Cold Stimulation

Neuropathic pain is a chronic disease state resulting from injury to the nervous system. This type of pain often responds poorly to standard treatments and occasionally may get worse instead of better over time. Patients who experience neuropathic pain report sensitivity to cold and mechanical stimuli. Since the nociceptive system of African naked mole-rats contains unique adaptations that result in insensitivity to some pain types, we investigated whether naked mole-rats may be resilient to sensitivity following nerve injury. Using the spared nerve injury model of neuropathic pain, we showed that sensitivity to mechanical stimuli developed similarly in mice and naked mole-rats. However, naked mole-rats lacked sensitivity to mild cold stimulation after nerve injury, while mice developed robust cold sensitivity. We pursued this response deficit by testing behavior to activators of transient receptor potential (TRP) receptors involved in detecting cold in naïve animals. Following mustard oil, a TRPA1 activator, naked mole-rats responded similarly to mice. Conversely, icilin, a TRPM8 agonist, did not evoke pain behavior in naked mole-rats when compared with mice. Finally, we used RNAscope to probe for TRPA1 and TRPM8 messenger RNA expression in dorsal root ganglia of both species. We found increased TRPA1 messenger RNA, but decreased TRPM8 punctae in naked mole-rats when compared with mice. Our findings likely reflect species differences due to evolutionary environmental responses that are not easily explained by differences in receptor expression between the species.

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