Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2011 Jul;106(1):274-9.
doi: 10.1152/jn.00141.2011. Epub 2011 May 11.

Abnormal muscle afferent function in a model of Taxol chemotherapy-induced painful neuropathy

Xiaojie Chen  1 , Paul G Green, Jon D Levine
Affiliations

Abnormal muscle afferent function in a model of Taxol chemotherapy-induced painful neuropathy

Xiaojie Chen et al. J Neurophysiol. 2011 Jul.

Abstract

Despite muscle pain being a well-described symptom in patients with diverse forms of peripheral neuropathy, the role of neuropathic mechanisms in muscle pain have received remarkably little attention. We have recently demonstrated in a well-established model of chemotherapy-induced painful neuropathy (CIPN) that the anti-tumor drug paclitaxel (Taxol) produces mechanical hyperalgesia in skeletal muscle, of similar time course to and with shared mechanism with cutaneous symptoms. In the present study, we evaluated muscle afferent neuron function in this rat model of CIPN. The mechanical threshold of muscle afferents in rats exposed to paclitaxel was not significantly different from the mechanical threshold of muscle afferents in control animals (P = 0.07). However, paclitaxel did produce a marked increase in the number of action potentials elicited by prolonged suprathreshold fixed intensity mechanical stimulation and a marked increase in the conduction velocity. In addition, the interspike interval (ISI) analysis (to evaluate the temporal characteristics of the response of afferents to sustained mechanical stimulation) showed a significant difference in rats treated with paclitaxel; there was a significantly greater ISI percentage of paclitaxel-treated muscle afferents with 0.01- and 0.02-s ISI. In contrast, an analysis of variability of neuronal firing over time (CV2 analysis) showed no effect of paclitaxel administration. These effects of paclitaxel on muscle afferent function contrast with the previously reported effects of paclitaxel on the function of cutaneous nociceptors.

PubMed Disclaimer

Figures

Fig. 1.
Fig. 1.
Mechanical threshold of muscle afferents. Mechanical threshold in afferents innervating the gastrocnemius muscle of paclitaxel-treated rats were not significantly different from the threshold in afferents from naïve control rats. Scattergram of mechanical thresholds of individual muscle afferents from naïve control and paclitaxel-treated rats is also shown.
Fig. 2.
Fig. 2.
Response of muscle afferents to a sustained mechanical stimulus. The responses of afferents innervating the gastrocnemius muscle of paclitaxel-treated rats to mechanical stimuli (60-s suprathreshold 10-g von Frey hair, n = 31) were significantly higher than those of control rats (n = 40; *P < 0.05). Scattergram of individual responses of muscle afferents from naïve control and paclitaxel-treated rats is also shown.
Fig. 3.
Fig. 3.
Interspike interval (ISI) distribution of muscle afferents in response to sustained mechanical stimuli. No significant differences were observed in the ISI distribution of muscle afferents (from 0 to 0.28 s, in 0.01-s bin width, and >0.29 s), from control and paclitaxel-treated rats, in response to mechanical stimulation (60-s suprathreshold 10-g von Frey hair). *P < 0.05.
Fig. 4.
Fig. 4.
Conduction velocity in muscle afferents. Mean conduction velocities from paclitaxel-treated rats (2.09 ± 0.17 m/s, n = 31) were significantly greater than from naïve rats (1.25 ± 0.11 m/s, n = 40; Student's t-test, *P < 0.05). Scattergram of conduction velocities of muscle afferents in naïve control and paclitaxel-treated rats is also shown.
Fig. 5.
Fig. 5.
Paclitaxel treatment stress shifts muscle afferent conduction velocity frequency distribution. A plot of frequency distribution of conduction velocity indicates that there is a shift to faster conducting fibers in paclitaxel-treated rats. Graph overlay shows smoothing curve of data (6th order polynomial, 4 neighbor averaging) to illustrate shift in conduction velocity distribution.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Ahlgren SC, Levine JD. Protein kinase C inhibitors decrease hyperalgesia and C-fiber hyperexcitability in the streptozotocin-diabetic rat. J Neurophysiol 72: 684–692, 1994 - PubMed
    1. Alessandri-Haber N, Dina OA, Yeh JJ, Parada CA, Reichling DB, Levine JD. Transient receptor potential vanilloid 4 is essential in chemotherapy-induced neuropathic pain in the rat. J Neurosci 24: 4444–4452, 2004 - PMC - PubMed
    1. Alvarez P, Ferrari LF, Levine JD. Muscle pain in model of chemotherapy- and alcohol-induced peripheral neuropathy. Ann Neurol. doi:10.1002/ana.22382 - DOI - PMC - PubMed
    1. Arendt-Nielsen L, Sonnenborg FA, Andersen OK. Facilitation of the withdrawal reflex by repeated transcutaneous electrical stimulation: an experimental study on central integration in humans. Eur J Appl Physiol 81: 165–173, 2000 - PubMed
    1. Arnal I, Wade RH. How does taxol stabilize microtubules? Curr Biol 5: 900–908, 1995 - PubMed

Publication types

MeSH terms