The study of pain in awake animals raises ethical, philosophical, and technical problems. We review the ethical standards for studying pain in animals and emphasize that there are scientific as well as moral reasons for keeping to them. Philosophically, there is the problem that pain cannot be monitored directly in animals but can only be estimated by examining their responses to nociceptive stimuli; however, such responses do not necessarily mean that there is a concomitant sensation. The types of nociceptive stimuli (electrical, thermal, mechanical, or chemical) that have been used in different pain models are reviewed with the conclusion that none is ideal, although chemical stimuli probably most closely mimic acute clinical pain. The monitored reactions are almost always motor responses ranging from spinal reflexes to complex behaviors. Most have the weakness that they may be associated with, or modulated by, other physiological functions. The main tests are critically reviewed in terms of their sensitivity, specificity, and predictiveness. Weaknesses are highlighted, including 1) that in most tests responses are monitored around a nociceptive threshold, whereas clinical pain is almost always more severe; 2) differences in the fashion whereby responses are evoked from healthy and inflamed tissues; and 3) problems in assessing threshold responses to stimuli, which continue to increase in intensity. It is concluded that although the neural basis of the most used tests is poorly understood, their use will be more profitable if pain is considered within, rather than apart from, the body's homeostatic mechanisms.

Animal Models of Nociception

Assessing antidepressant activity in rodents: recent developments and future needs

Measuring reward with the conditioned place preference paradigm: a comprehensive review of drug effects, recent progress and new issues.

Much is known about the physiological impairments that can cause muscle fatigue. It is known that fatigue can be caused by many different mechanisms, ranging from the accumulation of metabolites within muscle fibres to the generation of an inadequate motor command in the motor cortex, and that there is no global mechanism responsible for muscle fatigue. Rather, the mechanisms that cause fatigue are specific to the task being performed. The development of muscle fatigue is typically quantified as a decline in the maximal force or power capacity of muscle, which means that submaximal contractions can be sustained after the onset of muscle fatigue. There is even evidence that the duration of some sustained tasks is not limited by fatigue of the principal muscles. Here we review experimental approaches that focus on identifying the mechanisms that limit task failure rather than those that cause muscle fatigue. Selected comparisons of tasks, groups of individuals and interventions with the task-failure approach can provide insight into the rate-limiting adjustments that constrain muscle function during fatiguing contractions.

https://physoc.onlinelibrary.wiley.com/doi/pdf/10.1113/jphysiol.2007.139477

Muscle fatigue: what, why and how it influences muscle function

The Life-Course Dynamics of Goal Pursuit and Goal Adjustment: A Two-Process Framework

Caffeine ingestion can delay fatigue during exercise, but the mechanisms remain elusive. This study was designed to test the hypothesis that blockade of central nervous system (CNS) adenosine recep...

Central nervous system effects of caffeine and adenosine on fatigue

While many individuals with anxiety disorders receive drug therapy, many do not respond or adversely respond to drugs. An alternative treatment, exercise, has been shown to relieve negative feelings and induce positive shifts in mood. The purpose of this study was to establish an animal model to specifically test the effects of chronic physical exercise on anxiety-related behaviors. Thirty-two male Sprague Dawley rats were divided into two groups: runners (R) and nonrunners (NR). Runners ran on a treadmill for 45 minutes a day, five days a week, for ten weeks at a moderate intensity. Nonrunners remained in their cages in the treadmill room during the running period and were handled for an equal amount of time. After ten weeks of training, two behavioral tests were administered including the elevated plus maze and open field tests. Results comparing R and NR showed higher responses by R in percent open arm time and center square time during the elevated plus maze test, as well as in number of entries into the center, number of rears, and lower fecal boli count during the open field test, p < 0.05. In addition, there were no differences in total activity levels between groups as indicated by similar closed arm entries in the elevated plus maze test and total lines crossed in the open field test. These results indicate that treadmill training reduces anxiety-like behaviors in two animal tests of anxiety, without a significant change in total activity levels. These data are in support of treadmill training as a model to test the anxiolytic effects of exercise.

Chronic physical exercise reduces anxiety-like behavior in rats.

Differential release of corticotropin-releasing hormone (CRH) in the amygdala during different types of stressors

Major depressive disorder (MDD) affects women to a greater extent then men; however, the few studies that have examined the role of gender in an animal model of depression have shown inconsistent results. The purpose of the present study was to determine if the gonadal hormone milieu of the animal modulated behavioral changes following olfactory bulbectomy (OBX), a well-documented animal model of depression. Body weight, sucrose preference levels and open-field activity levels were measured once a week for a period of 2 weeks in gonadally intact and gonadectomized male and female rats. Following these baseline measurements, animals underwent either OBX or sham surgery. Body weight, sucrose preference and activity levels were assessed for 4 weeks post-OBX surgery. OBX-gonadectomized animals exhibited higher activity levels than OBX gonadally intact and control animals. This effect of gonadectomy was more robust in males. OBX-females (both intact and gonadectomized) exhibited significantly lower sucrose preference levels than OBX-males (both intact and gonadectomized) and control animals. These results suggest that the gonadal hormone milieu of the animal plays a role in modulating sucrose preference and activity levels following OBX.

Gender and gonadal hormone effects in the olfactory bulbectomy animal model of depression.

Rationale: The demonstration of tolerance to the anxiolytic effects of benzodiazepines remains inconsistent. Objectives: The present study tested the hypothesis that intact and gonadectomized male and female rats might exhibit differential tolerance to the anxiolytic effects of diazepam (DZ). Methods: Following acute (3 days) or chronic (3 weeks) DZ exposure, all animals were tested on the elevated plus-maze and immediately sacrificed for analysis of corticosterone, adrenocorticotropin hormone, estrogen and progesterone levels in serum. In experiment 2, following acute or chronic DZ exposure, animals were treated with a DZ challenge dose on the test day. Results: In experiment 1, both acute and chronic DZ treatment similarly enhanced percentage open arm time and entries, regardless of the hormonal status of the animal. The results of experiment 2 showed that both acute and chronic DZ-treated animals exhibited a significantly higher percentage open arm time than control animals after the DZ challenge dose, and males and females did not differ in their responses to DZ exposure. Conclusions: The findings from these experiments suggest that tolerance to the anxiolytic effects of DZ did not develop in males or females, and that the hormonal status of the animal does not significantly alter the anxiolytic effects of DZ following either acute or chronic exposure. Following plus-maze exposure, females had significantly higher corticosterone levels than males and acute DZ treatment diminished this stress response.

Howard S. Stock

Papers

Central nervous system effects of caffeine and adenosine on fatigue

Chronic physical exercise reduces anxiety-like behavior in rats.

Differential release of corticotropin-releasing hormone (CRH) in the amygdala during different types of stressors

Gender and gonadal hormone effects in the olfactory bulbectomy animal model of depression.

A lack of tolerance to the anxiolytic effects of diazepam on the plus-maze: comparison of male and female rats