Research paperAltered temporal pattern of evoked afferent activity in a rat model of vincristine-induced painful peripheral neuropathy
Section snippets
Animals
Experiments were performed on 200–400-g male Sprague–Dawley rats (Bantin and Kingman, Fremont, CA, USA). Rats were housed in a temperature- and humidity-controlled environment and were maintained on a 12-h light/dark cycle. Food and water were available ad libitum. Experiments were approved by the Committee on Animal Research at UCSF, and were carried out in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals. All efforts were made to minimize
Vincristine-induced hyperresponsiveness in a subset of C-fiber nociceptors
A subset (41%) of C-fiber nociceptors become hyperresponsive in vincristine-treated rats, firing more than twice as many action potentials in response to a 1-min 10-g mechanical stimulus compared with C-fibers in untreated control rats or to non-hyperresponsive C-fiber nociceptors in vincristine-treated rats (Tanner et al., 1998b). There were no significant differences between the conduction velocities and mechanical thresholds of hyperresponsive vincristine-treated C-fibers compared with
Are the increase in variability and shift in interspike interval distribution specific effects of vincristine or mere consequences of the fibers’ firing at a higher frequency?
It could be hypothesized that the distinctive variable firing patterns we observed in hyperresponsive nociceptors may not be caused by specific vincristine-induced alterations in function, but instead may simply be a consequence of firing at twice the average frequency exhibited by control or non-hyperresponsive vincristine-treated nociceptors. It is difficult to test this experimentally because it has not been possible to drive control nociceptors to fire at as high an average frequency as is
Conclusions
This study demonstrates that the temporal structure of responses in a subpopulation of nociceptive nerve fibers is altered in the vincristine-induced neuropathic pain state. In the subset of C-fiber nociceptors with increased firing rates, the level of variability in interspike intervals at the higher firing rates exceeds that which occurs in normal fibers. We speculate that this distinctive increase in variability might exacerbate pain by promoting synaptic plasticity in central sensory
Acknowledgements
The authors thank Dr. Ken Miller (Sloane Center for Computational Neuroscience and Keck Center for Integrative Neuroscience) for advice on developing the analytical model. This research was supported by NIH (NS21647 and DE08973) and the American Cancer Society. KDT was supported by a NSF Predoctoral Fellowship and an American Heart Association Predoctoral Fellowship.
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2011, NeuroscienceCitation Excerpt :ISI analysis, used to evaluate the temporal characteristics of the response of C-fiber nociceptors to sustained mechanical stimulation, was adopted from our study of nociceptor activity in the rat model of vincristine-induced painful neuropathy (Tanner et al., 2003). The ISIs for the responses of each C-fiber were grouped into 100 ms bins between 0 and 499 ms; the few ISIs greater than or equal to 500 ms were not analyzed (Tanner et al., 2003). This bin width also allows comparison of data with that from previous studies (Arendt-Nielsen et al., 2000; Franck et al., 1993; Miller and Woolf, 1996).
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