Detection and Assessment of Xenobiotic‐Induced Sensory Neuropathy

J. David Clark1

1 Stanford University and VAPAHCS, Palo Alto, California
Publication Name:  Current Protocols in Toxicology
Unit Number:  Unit 11.13
DOI:  10.1002/0471140856.tx1113s22
Online Posting Date:  January, 2005
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Amongst the adverse effects of xenobiotics used for industrial or therapeutic purposes is the tendency of some compounds to cause painful sensory neuropathies. Chemotherapeutic agents, antiretrovirals, metals, and many other classes of compounds have been reported to cause such neuropathies. These conditions can be assessed in rodent models during short‐ or long‐term exposure. In this unit, two methods for the detection of xenobiotic‐induced neuropathies are discussed. The first assay uses noxious thermal stimulation of the rat hind paw to follow changes in sensitivity as might occur with a progressive peripheral neuropathy. The second method involves the application of nylon von Frey filaments to the hind paw of the rodent to assess the development of decreasing nociceptive thresholds as might occur in the setting of a painful peripheral neuropathy.

Keywords: Neuropathy; Pain; von Frey filaments; Sensory; Thermal

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Table of Contents

  • Basic Protocol 1: Thermal Paw Flick Assay
  • Basic Protocol 2: Mechanical Von Frey Assay
  • Commentary
  • Literature Cited
  • Tables
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Basic Protocol 1: Thermal Paw Flick Assay

  • Rats
  • Thermal paw flick (Hargreaves) apparatus (IITC model 390 or similar)
  • Enclosures (if not included with other testing apparatus): ∼15 × 15–cm area and ∼30‐cm high (if no lid is used) clear plastic (rats should not be restrained within enclosures)

Basic Protocol 2: Mechanical Von Frey Assay

  • Rats
  • Mesh platforms (IITC model 410 or similar)
  • von Frey fibers: sets of individual fibers or calibrated instruments of various designs are available (e.g., IITC model 2290 or Stoelting model 58011)
  • Enclosures (if not included with other testing apparatus): ∼15 × 15–cm area and ∼30‐cm height (if no lid is used) clear plastic
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Literature Cited

Literature Cited
   Authier, N., Gillet, J.P., Fialip, J., Eschalier, A., and Coudore, F. 2000. Description of a short‐term Taxol‐induced nociceptive neuropathy in rats. Brain Res. 887:239‐2349.
   Bodnar, R.J. and Hadjimarkou, M.M. 2003. Endogenous opiates and behavior: 2002. Peptides 24:1241‐1302.
   Chaplan, S.R., Bach, F.W., Pogrel, J.W., Chung, J.M., and Yaksh, T.L. 1994. Quantitative assessment of tactile allodynia in the rat paw. J. Neurosci. Methods 53:55‐63.
   Dieterich, D.T. 2003. Long‐term complications of nucleoside reverse transcriptase inhibitor therapy. AIDS Read 13:176‐184.
   Fields, H.L. 2000. Pain modulation: Expectation, opioid analgesia and virtual pain. Prog. Brain Res. 122:245‐253.
   Hargreaves, K., Dubner, R., Brown, F., Flores, C., and Joris, J. 1988. A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia. Pain 32:77‐88.
   Levin, S., Pearsall, G., and Ruderman, R.J. 1978. Von Frey's method of measuring pressure sensibility in the hand: an engineering analysis of the Weinstein‐Semmes pressure aesthesiometer. J. Hand Surg. [Am] 3:211‐216.
   Li, X., Angst, M.S., and Clark, J.D. 2001. A murine model of opioid‐induced hyperalgesia. Brain Res. Mol. Brain Res. 86:56‐62.
   Peltier, A.C. and Russell, J.W. 2002. Recent advances in drug‐induced neuropathies. Curr. Opin. Neurol. 15:633‐638.
   Pogatzki, E.M., Gebhart, G.F., and Brennan, T.J. 2002. Characterization of Adelta‐ and C‐fibers innervating the plantar rat hindpaw one day after an incision. J. Neurophysiol. 87:721‐731.
   Sandkuhler, J. 1996a. Neurobiology of spinal nociception: New concepts. Prog. Brain Res. 110:207‐224.
   Sandkuhler, J., 1996b. The organization and function of endogenous antinociceptive systems. Prog. Neurobiol. 50:49‐81.
   Verstappen, C.C., Heimans, J.J., Hoekman, K., and Postma, T.J. 2003. Neurotoxic complications of chemotherapy in patients with cancer: Clinical signs and optimal management. Drugs 63:1549‐1563.
   Visovsky, C. 2003. Chemotherapy‐induced peripheral neuropathy. Cancer Invest. 21:439‐451.
   Yeomans, D.C., Pirec, V., and Proudfit, H.K. 1996. Nociceptive responses to high and low rates of noxious cutaneous heating are mediated by different nociceptors in the rat: Behavioral evidence, Pain 68:133‐140.
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