Elsevier

Neuroscience

Volume 105, Issue 1, 16 July 2001, Pages 265-275
Neuroscience

Hyperexcitability in sensory neurons of rats selected for high versus low neuropathic pain phenotype

https://doi.org/10.1016/S0306-4522(01)00161-0Get rights and content

Abstract

Selection line rats congenitally high or low for autotomy in the neuroma model of neuropathic pain (HA and LA rats) were found to be correspondingly high and low in a second type of neuropathic pain, the Chung model, which employs an alternative phenotypic endpoint, tactile allodynia. It has been proposed that both phenotypes reflect ectopic hyperexcitability in axotomized primary sensory neurons. To test this hypothesis we made in vitro recordings from sensory neurons in the L4 and 5 dorsal root ganglia. Baseline excitability was similar in HA and LA rats, and axotomy caused an increase in both lines. However, in the one neuronal subclass previously linked to neuropathic pain in these models the increase was significantly greater in HA than LA rats, and only at the time when pain scores in the two lines were diverging.

Heritable differences in electrical response to axotomy in a specific afferent cell type appear to be a fundamental determinant of neuropathic pain.

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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