Elsevier

Neuroscience

Volume 137, Issue 3, 2006, Pages 961-970
Neuroscience

Pain mechanism
The effect of site and type of nerve injury on the expression of brain-derived neurotrophic factor in the dorsal root ganglion and on neuropathic pain behavior

https://doi.org/10.1016/j.neuroscience.2005.10.015Get rights and content

Abstract

A number of rat neuropathy models have been developed to simulate human neuropathic pain conditions, such as spontaneous pain, hyperalgesia, and allodynia. In the present study, to determine the relative importance of injury site (proximal or distal to the primary afferent neurons) and injury type (motor or sensory), we examined pain-related behaviors and changes of brain-derived neurotrophic factor expression in the dorsal root ganglion in sham-operated rats, and in the L5 dorsal rhizotomy, L5 ventral rhizotomy, L5 dorsal rhizotomy+ventral rhizotomy, and L5 spinal nerve transection models. L5 ventral rhizotomy and spinal nerve transection produced not only mechanical and heat hypersensitivity, but also an increase in brain-derived neurotrophic factor mRNA/protein in the L5 dorsal root ganglion at 7 days after surgery. In contrast, rats in the L5 dorsal rhizotomy and dorsal rhizotomy+ventral rhizotomy groups did not show both pain behaviors at 7 days after surgery, despite brain-derived neurotrophic factor upregulation in medium- and large-size neurons in the L5 dorsal root ganglion. On the other hand, L5 spinal nerve transection, but not dorsal rhizotomy, dorsal rhizotomy+ventral rhizotomy or ventral rhizotomy, increased the expression of brain-derived neurotrophic factor in the L4 dorsal root ganglion at 7 days after surgery. Taken together, these findings suggest that the upregulation of brain-derived neurotrophic factor expression in the L4 and L5 dorsal root ganglion neurons may be, at least in part, involved in the pathophysiological mechanisms of neuropathic pain and that the selective nerve root injury models may be useful for studying the underlying mechanisms of chronic pain after nerve injury.

Section snippets

Animals

A total of 40 male Sprague–Dawley rats weighing 200–250g were used. All animal experimental procedures were approved by the Hyogo College of Medicine Committee on Animal Research and were carried out in accordance with the guidelines of the National Institutes of Health on animal care. Every effort was undertaken to minimize the number of animals used and their discomfort.

Surgical procedures

All experimental procedures were performed on rats that were deeply anesthetized with sodium pentobarbital (50mg/kg body

Neuropathic pain behavior

The time course of mechanical allodynia and heat hyperalgesia in the sham, DR, DR+VR, VR and SNT groups of rats is shown in Fig. 2 (n=8 in each group). Before surgery, rats rarely withdrew their paws from the innocuous mechanical stimuli applied to the plantar surface of the hind paw. Rats in the sham, DR and DR+VR groups did not show a significant change in response frequency (Fig. 2A, C and E, respectively). In contrast, most rats in the VR and SNT groups developed mechanical allodynia to

Discussion

The present study demonstrated the following new findings: (1) Rats in the L5 DR and DR+VR groups did not show both pain behaviors at 7 days after surgery, despite BDNF upregulation in medium- and large-size neurons in the L5 DRG. (2) L5 SNT, but not DR, DR+VR or VR, increased the expression of BDNF in the L4 DRG at 7 days after surgery.

Acknowledgments

This work was supported in part by grants-in-aid for scientific research and a grant from the Open Research Center, Hyogo College of Medicine, from the Japanese Ministry of Education, Science, and Culture. This work was also supported by grant-in-aid for Researchers, Hyogo College of Medicine. We thank Yuki Obata and Nobumasa Ushio for technical assistance. We thank Dr. D. A. Thomas for correcting the English usage.

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