Behavioral indices of ongoing pain are largely unchanged in male mice with tissue or nerve injury-induced mechanical hypersensitivity

Abstract

Despite the impact of chronic pain on the quality of life in patients, including changes to affective state and daily life activities, rodent preclinical models rarely address this aspect of chronic pain. To better understand the behavioral consequences of the tissue and nerve injuries typically used to model neuropathic and inflammatory pain in mice, we measured home cage and affective state behaviors in animals with spared nerve injury (SNI), chronic constriction injury (CCI) or intraplantar CFA. Mechanical hypersensitivity is prominent in each of these conditions and persists for many weeks. Home cage behavior was continuously monitored for 16 days in a system that measures locomotion, feeding and drinking and allows for precise analysis of circadian patterns. When monitored after injury, animals with SNI and CFA behaved no differently from controls in any aspect of daily life. Animals with CCI were initially less active, but the difference between CCI and controls disappeared by 2 weeks after injury. Further, in all pain models, there was no change in any measure of affective state. We conclude that in these standard models of persistent pain, despite the development of prolonged hypersensitivity, the mice do not have significantly altered "quality of life". As alteration in daily life activities is the feature that is so disrupted in patients with chronic pain, our results suggest that the models used here do not fully reflect the human conditions and point to a need for development of a murine chronic pain model in which lifestyle changes are manifest.

Chronic Constriction of the Sciatic Nerve and Pain Hypersensitivity Testing in Rats

“…Following CCI, rats exhibit abnormal posture of the injured hindpaw (toes held together and plantar-flexed and paw everted), as well as repeated shaking, guarding and licking of the injured hindpaw suggesting the presence of spontaneous pain 9 . In addition to sensory dysfunction, several investigators have shown that CCI evokes behavioural disabilities, such as disrupted social interactions, sleep disturbances, depressive-like and anxiety-like behaviours [10][11][12][13] , however this is in contrast to the failure to find such behavioural disabilities by others 14,15 . CCI is therefore commonly used to investigate both the pathophysiology, and potential therapeutic agents for treatment of neuropathic pain.…”

“…It is noteworthy that several variations to the original procedure have been reported including using only 2 ligatures around the nerve 16,17 and using suture material other than chromic gut such as plain gut and polyglactin (vicryl) 18,19 in rats. In addition, the CCI model has also been modified for use in mice, where the procedure is identical, except for the use of 2-3 ligatures with various suture materials including chromic gut, nylon, and prolene 15,20,21 .…”

The power of automated behavioural homecage technologies in characterizing disease progression in laboratory mice: A review

“…Changes in activity and exploratory behaviours are common and have been noted in mice with cancer. For example, mice developing SL2 lymphoma spend less time rearing as disease progresses (van Loo et al, 1997). Other common changes include decreased food and water consumption (Jacobsen et al, 2013) which is often accompanied by weight loss, the most frequently measured parameter used to monitor laboratory animals (Dallman, 2000).…”

“…There are also likely to be considerable biomedical benefits to characterizing behavioural changes that occur with disease. There has been increasing concern about animal studies translating poorly to human patients with a contributing factor being that animal studies do not always sufficiently reflect disease in humans (van der Worp et al, 2010). Identification of the mouse models of disease that more closely replicate human disease phenotypes may improve their predictive validity (McGonigle and Ruggeri, 2014).…”

“…Compared to behavioural changes that occur with progressive disease, the automated detection of behavioural changes that occur in pain states have been relatively well described (e.g. Roughan et al, 2009;Miller et al, 2011Miller et al, , 2012Urban et al, 2011;Wright-Williams et al, 2013;Whittaker and Howarth, 2014), and will therefore not be discussed further here.…”