Hyperexcitability in sensory neurons of rats selected for high versus low neuropathic pain phenotype
Section snippets
Animals and surgery
Experiments used adult (215–544 g) HA and LA rats of both sexes that had been selected for high versus low autotomy from a base population of Wistar-derived Sabra strain rats (Lutzky et al., 1984) as described by Devor and Raber (1990). All procedures followed national and University regulations for the humane care and use of laboratory animals, and the ethical guidelines of the International Association for the Study of Pain (Zimmermann, 1983). In particular, efforts were made to minimize
Heritability in the neuroma model of neuropathic pain
The HA/LA selection lines were generated from outbred Wistar-derived Sabra strain rats by repeated cycles of phenotyping followed by selective breeding as described by Devor and Raber (1990). For the HA line we bred male and female offspring that had the highest autotomy scores, and for the LA line those with the lowest autotomy scores. Brother–sister matings were avoided to reduce the rate of fixation of non-selected alleles within each line. Rats used for measurements of tactile allodynia
Discussion
Selection line rats congenitally high and low (HA, LA) for pain phenotype in the neuroma model of neuropathic pain were correspondingly high and low for pain phenotype in the Chung model. Baseline excitability of DRG neurons was similar in the two lines. However, in the one neuronal subclass previously linked to neuropathic pain in these models, axotomy caused a significantly greater increase in excitability in HA than LA rats. Moreover, this difference occurred only at the time when pain
Conclusions
Our working hypothesis (Devor and Seltzer, 1999) is that the intense ongoing activity in axotomized A0 afferents in HA versus LA rats generates ongoing abnormal sensation referred to the denervated limb (anesthesia dolorosa or an unpleasant phantom). In addition this activity, perhaps together with low level ectopic activity generated in C-neurons, also supports central sensitization. In the neuroma model central sensitization causes the phantom evoked by ectopic A0-fiber activity to be
Acknowledgements
Supported by grants from the German–Israel Foundation for Research and Development (GIF), and the Fritz Thyssen Stiftung. C.-N.L. received a Golda Meir post-doctoral fellowship.
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