Hyper-responsivity in a subset of C-fiber nociceptors in a model of painful diabetic neuropathy in the rat
Section snippets
Animal model
Sprague–Dawley rats (280–320 g) from Bantin & Kingman (Fremont, CA, USA) were injected with STZ (70 mg/kg, s.c.; Sigma, St Louis, MO, USA). The onset of the diabetic state appeared one to three days after injection of STZ, as assessed by the presence of increased glucose (>500 mg/dl; Keto-Diastix®, Bayer) and ketone (>40 mg/dl; Keto-Diastix®, Bayer) in the rat’s urine. The diabetic rats were housed individually on deep wood-chip bedding, and provided with 0.45% saline for drinking and standard rat
General characteristics of C-fibers that are unchanged in diabetes
The location of receptive fields of C-fibers from control and diabetic rats was similar. In the absence of stimulation, most of the C-fibers studied from control (91%) and diabetic (85%) rats had no ongoing activity; the few fibers that did fired at less than 0.04 Hz. The mean values of conduction velocities from control and diabetic rats were 0.89±0.07 and 0.88±0.04 m/s, respectively (P>0.05; Fig. 1A). The distribution of the mechanical thresholds for C-fibers from diabetic and control rats was
Discussion
While the mechanical threshold of C-fibers in STZ-diabetic rats was not significantly different from that of C-fibers in control rats, sustained mechanical stimulation elicited significantly more action potentials in C-fibers in diabetic rats. This finding is similar to what has been observed in the vincristine model of chemotherapy-induced painful neuropathy26 and in a model of traumatic neuropathy.21 Since all C-fibers do not have the same threshold, the finding of no change in C-fiber
Conclusions
We describe alterations in C-fiber responsivity detectable in a model of painful diabetic neuropathy, which suggest that changes in a subset of nociceptors may contribute to the enhanced nociception seen in painful diabetic neuropathy.
Acknowledgements
This research was supported by NIH grant DE08973. We would like to thank Drs David Reichling and Phillip Heller for helpful comments on the manuscript, and Drs Sachia Khasar and Dennis Mendoza for assistance with the rat model of diabetic neuropathy.
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