Altered temporal pattern of mechanically evoked C-fiber activity in a model of diabetic neuropathy in the rat

Neuroscience. 2003;121(4):1007-15. doi: 10.1016/s0306-4522(03)00486-x.


While enhanced nociceptor activity has been demonstrated in models of painful peripheral neuropathy, analyses of activity pattern, which could play a role in the symptoms experienced as well as help elucidate underlying mechanism, are still limited. We evaluated the pattern of C-fiber activity, in response to mechanical and chemical stimuli, in a rat model of diabetes induced by a pancreatic beta-cell toxin, streptozotocin (STZ). In diabetic rats the number of action potentials produced by threshold and suprathreshold (10 g) sustained (60 s) mechanical stimuli was elevated in approximately half of C-fibers. These high-firing C-fibers demonstrated a disproportionate increase in interspike intervals (ISIs) between 100 and 199 ms, compared with low-firing diabetic and control C-fibers. The co-efficient of variability (CV2), a frequency independent measure of ISI variability, was also greater in high-firing fibers, compared with control fibers. Unexpectedly, instantaneous frequency of the initial burst of activity during the first second was lower in high-firing fibers, even though the average frequency over the last 59 s was significantly higher. The number of action potentials evoked by a noxious chemical stimulus, 300 and 600 mM KCl, injected adjacent to the mechanical receptive field was also significantly increased in C-fibers from diabetic rats and mechanically high-firing fibers had more action potentials in response to KCl than control fibers and a disproportionate increase in ISIs between 100 and 199 ms for responses to chemical stimuli appeared only in mechanically high-firing C-fibers, compared with the mechanically low-firing diabetic or control C-fibers. There was, however, no corresponding change in CV2 or instantaneous frequency plots for the response to chemical stimulation in mechanically high-firing fibers, as there was in the response to mechanical stimulation. Our data demonstrate specific changes in firing pattern of high-firing C-fibers in the rat model of painful neuropathy produced by STZ-diabetes that might contribute to the symptoms experienced by patients.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / physiology*
  • Animals
  • Diabetes Mellitus, Experimental / physiopathology
  • Diabetic Neuropathies / physiopathology*
  • Disease Models, Animal
  • Mechanoreceptors / drug effects
  • Mechanoreceptors / physiopathology*
  • Nerve Fibers, Unmyelinated / drug effects
  • Nerve Fibers, Unmyelinated / physiology*
  • Nociceptors / drug effects
  • Nociceptors / physiopathology*
  • Physical Stimulation
  • Potassium Chloride / pharmacology
  • Rats
  • Rats, Sprague-Dawley


  • Potassium Chloride