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Thread: Chronic central pain syndrome in rat spinal cord injury models

  1. #1

    Chronic central pain syndrome in rat spinal cord injury models

    • Mills CD, Hains BC, Johnson KM and Hulsebosch CE (2001). Strain and model differences in behavioral outcomes after spinal cord injury in rat. J Neurotrauma. 18 (8): 743-56. Summary: Spinal cord injury (SCI) results in loss of function below the level of injury and the development of chronic central pain (CCP) syndromes. Since different strains may develop and express chronic pain behaviors differently, we evaluated behavioral outcomes (locomotor recovery and the development of mechanical and thermal allodynia) in three commonly used strains of rats (Long-Evans, Wistar, and Sprague-Dawley) using two models of SCI. The two models examined were contusion at T10 (NYU impactor, 12.5 mm height) and the T13 hemisection. Mechanical stimulation (von Frey filaments) revealed significantly lower baseline responses for Long-Evans rats and significantly higher baseline paw withdrawal latencies to thermal stimulation for Wistar rats compared to the other strains. Following contusion SCI, Long-Evans rats had the highest percentage of animals that developed mechanical allodynia (73%), while Sprague-Dawley rats had the highest percentages (75%) following hemisection SCI. Interestingly, the Sprague-Dawley rats had the highest percentage (87%) to develop thermal allodynia following contusion SCI, while 100% of both Long-Evans and Sprague Dawley rats developed thermal allodynia in the hemisection model. Locomotor recovery after SCI was similar for each model in that Long-Evans rats recovered slower and to a lesser extent than the other strains. In each model, Sprague-Dawley rats recovered faster and achieved greater function. Overall, the hemisection model produced a larger percentage of animals that developed CCP and had greater responses to mechanical stimulation. Thus, it appears that strain selection has a greater impact on locomotor recovery and model selection has a greater impact on the development of CCP following SCI. Furthermore, these results suggest that genetic factors may play a role in recovery following SCI. <http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11526981> Department of Anatomy and Neurosciences. University of Texas Medical Branch at Galveston, 77555-1043, USA.

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    I've followed a little of Claire Hulsebosch's (one of the authors of this study) work in the past and I've been fairly impressed with what she's done. This article is an excellent example of the importance of variables that can sometimes be so easy to overlook; in this case the specific strain of rat. Ultimately, it alludes to the challenge that researchers face. They're working on rats, as opposed to humans, for obvious reasons, but at the same time you have to always keep in mind how different the results can be under different circumstances.

    One unfortunate consequence of using animal models for research is that you almost inevitably wind up bypassing answers that would work great in humans, but you'll never know because you weren't working with humans. It's the trade-off you have to accept when you use lab animals in cases such as this.

    I believe it was Zsuzsanna Wiesenfeld-Hallin of the Karolinska Institute in Sweden who developed the animal model for central pain. Karolinska isn't too familiar to a lot of Americans, but it's one of the premier research institutes in Europe. I read on their site that 45% of Sweden's research funds go to Karolinska, and they do some great work. Wiesenfeld-Hallin now leads a team of researchers there, and I try to keep half an eye posted for work coming from that direction.

    David Berg

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    I neglected to include the link to a study led by Wiesenfeld-Hallin. It's not her latest work, but it's a good example of what she's involved with and it was one of the first ones I could lay my fingers on:Central Inhibitory Dysfunctions

    One more thing in the original post on this thread that caught my attention. VonFrey hairs are often used as a tool to test response feedback in studies with rats. The only clinician I've heard of so far that uses them regularly with patients is Ron Tasker in Toronto. From what I can see, they're an excellent example of a cheap, simple, and effective clinical tool to help assess touch sensation. I think it's a bit of a shame that they seem to take such a backseat to the high-tech instruments that you virtually never hear of them. I might be wrong about all of this, and there might be many more docs out there using them that I realize. I'm not down at all on high-tech, I just like to see the simple clinical tools that are available used as well.

    David Berg

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    I also know and like Claire. I have to say, however, that we have tried testing for allodynia in rats and it is not very easy or straightforward. You poke the rat with these Von Fry hairs and listen to whether the rats squeak or not. Sometimes they do, sometimes they just don't feel like it even though the poking may be a pain in the poke. In any case, it is very hard work to evaluate the rats. It is too bad that they can't squeak the rating on a visual analog scale. They probably can be trained to do so (anything is possible...) but then the rat would be so precious you would never want to do the experiment. Sigh.

    Wise.

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    Wise, have you ever heard about the former lab rat that was trained to run network wires through ductwork?

    I had to smile when you mentioned the difficulty in perceiving allodynia in rats. Just this evening my wife asked me how researchers can be positive exactly what symptoms rats are feeling, and how they can be sure what the rats are experiencing is central pain, at least in the same way that humans have central pain. I suppose the only real answer to that is that ultimately the researcher is forced to anthropomorphize the rats to some extent. My son's comment on the issue was that some gorillas can do sign language but then, of course, the gorillas can hit back if you give them central pain and go poking around on them.

    I'll have to say that I've seen enough vague definitions for "allodynia" that I'm convinced that not everyone who uses the term in studies has the same thing in mind.

    David Berg

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