Inflicting Sciatic Pain in Rats

“A novel animal model of graded neuropathic pain: Utility to investigate mechanisms of population heterogeneity”, Peter M. Grace, Mark R. Hutchinson, Jim Manavis, Andrew A. Somogyi, and Paul E. Rolan.

University of Adelaide and the Hanson Institute, Adelaide

Published in Journal of Neuroscience Methods (2010); 193: 47-53.

Aim

To study pain originating in the nervous system in a rat model

The experiment

Twenty eight male rats were divided into groups and underwent invasive surgery in which the main nerve of the hind leg (the sciatic nerve) was tied with suture material (chromic gut sutures). A “control” group of rats underwent anaesthesia during which the sciatic nerve was exposed but not tied.

The remaining rats had either, one, two or four sutures tied around the sciatic nerve. Those with fewer than four sutures received additional pieces of suture material placed in the hip area (under the skin), in order to provoke an inflammatory body response in addition to the effects of the sutures tied around the sciatic nerve. A characteristic of chromic gut sutures is that they swell, which would result in a further constriction (tightening) around the sciatic nerve.

An analogous situation in humans would be a person suffering from the condition known as “sciatica”.

[Sciatica is a set of symptoms including pain that may be caused by general compression and/or irritation of one of five spinal nerve roots that give rise to each sciatic nerve, or by compression or irritation of the left or right or both sciatic nerves. The pain is felt in the lower back, buttock, and/or various parts of the leg and foot. In addition to pain, which is sometimes severe, there may be numbness, muscular weakness, pins and needles or tingling and difficulty in moving or controlling the leg.”[1]]

After recovering from the surgery, the rats underwent behavioural tests which consisted of applying stiff filaments to the feet of the hindpaws in order to elicit a withdrawal response. It should be noted that the authors describe this sensation as “allodynia” (defined as an uncomfortable heightened sensitivity to touch).

All of the rats were killed at the end of the experiment and their spinal cords examined.



Results

The authors were able to demonstrate that the rats became more sensitive to the filaments as the days of the experiment progressed, as a result of the increased inflammation and nerve constriction. This effect was most noticeable in rats with the most number of sutures tied around their sciatic nerve.

Conclusion

The authors conclude that this study achieved their aim of developing a model of variable pain response (“graded behavioural allodynia”), which was achieved simply by varying the number of chromic gut sutures tied around the sciatic nerve and pieces placed in the hip area. This result, in the view of the authors, “moves the preclinical model closer to the clinical experience of pain that occurs with a broad range of pain sensitivities”.

Note that the same authors continue to publish pain studies in rodents.

What can you do?

Contact the university and ask them how their rat model is predictive for humans. Also ask whether the Category C (animal welfare) representative on the ethics committee which approved this experiment is suitably qualified to question the scientific justification of this research.

AEC Secretary

Research Ethics and Compliance Unit

University of Adelaide

SA 5005

rb@adelaide.edu.au

Critique of the study by Dr Andre Menache

Animal welfare considerations

The authors make no mention in the paper of whether any post-operative analgesia was administered to the rats during the recovery period prior to the behavioural phase of the study. The authors do mention the absence of signs of post-operative infection but for some reason fail to mention the presence of post-operative signs of pain. There is also no mention of the physical condition of the animals during the 14-day and 29-day behavioural testing phase. For example, were the animals regularly weighed to check for signs of weight loss resulting from decreased appetite associated with pain?

 

Cost-benefit assessment

The authors make no mention of the “severity banding” submitted by them to the Animal Ethics Committee. For example, the authors may have classed the level of pain expected to occur in their experimental subjects as “mild to moderate” whereas the actual situation could better be described as “moderate to severe”. Considering the pain and suffering that the rats were subjected to (invasive surgery, followed by moderate to severe nerve pain, followed by distressing behavioural tests), and considering that this study is a minor variation on a well-worn theme, it is difficult to justify the current level of suffering from a cost-benefit perspective.

 

Methodological issues

The study exhibits some of the characteristics of a study in “fundamental research” (the discovery of new knowledge for its own sake) but in their introduction, the authors make a point of wanting to apply the results of their work to “millions of people world wide”. For this, and other reasons, the study falls outside the boundaries of fundamental research. However, it is well worth critiquing the experiment from both angles (i.e. basic and applied research), so as to address both options and any overlap between the two.

 

While animal researchers often try to justify their studies (especially in fundamental research) by relying on reductionist thinking, complexity theory clearly demonstrates that evolved living systems (such as mammals) are far more than the sum of their individual cells or organ systems. While reductionist theory can be applied to simple organisms, it is not suited to understanding complex living systems.

 

According to molecular biologist Marc van Regenmortel:

“The reductionist method of dissecting biological systems into their constituent parts has been effective in explaining the chemical basis of numerous living processes. However, many biologists now realize that this approach has reached its limit. Biological systems are extremely complex and have emergent properties that cannot be explained, or even predicted, by studying their individual parts. The reductionist approach - although successful in the early days of molecular biology - underestimates this complexity and therefore has an increasingly detrimental influence on many areas of biomedical research, including drug discovery and vaccine development.”[1]



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