 |
|||||
|
|||||
|
|||||
|
|||||
|
|||||
Previous Article | Next Article
The Journal of Neuroscience, April 1, 2003, 23(7):2911
Resiniferatoxin Induces Paradoxical Changes in Thermal and Mechanical Sensitivities in Rats: Mechanism of Action
Hui-Lin Pan1, 2, Ghous M. Khan1, Kevin D. Alloway2, and Shao-Rui Chen1 Departments of 1 Anesthesiology and 2 Neuroscience and Anatomy, The Pennsylvania State University College of Medicine, The Milton S. Hershey Medical Center, Hershey, Pennsylvania 17033-0850
Resiniferatoxin (RTX), an ultrapotent analog of capsaicin, has been used as a tool to study the role of capsaicin-sensitive C fibers in pain. Recently, we found that RTX diminished the thermal sensitivity but unexpectedly increased the sensitivity to tactile stimulation in adult rats. In this study, we explored the potential mechanisms involved in RTX-induced changes in somatosensory function. An intraperitoneal injection of 200 µg/kg RTX, but not its vehicle, rapidly produced an increase in the paw withdrawal latency to a heat stimulus. Also, profound tactile allodynia developed in all the RTX-treated rats in 3 weeks. This paradoxical change in thermal and mechanical sensitivities lasted for at least 6 weeks. Electron microscopic examination of the sciatic nerve revealed a loss of unmyelinated fibers and extensive ultrastructural damage of myelinated fibers in RTX-treated rats. Immunofluorescence labeling showed a diminished vanilloid receptor 1 immunoreactivity in dorsal root ganglia neurons and the spinal dorsal horn of RTX-treated rats. Furthermore, two transganglionic tracers, horseradish peroxidase conjugates of cholera toxin B subunit (CTB) and isolectin-B4 of Bandeiraea simplicifolia (IB4), were injected into the opposite sides of the sciatic nerve to trace myelinated and unmyelinated afferent terminations, respectively, in the spinal dorsal horn. In RTX-treated rats, IB4-labeled terminals in the dorsal horn were significantly reduced, and CTB-labeled terminals appeared to sprout into lamina II of the spinal dorsal horn. Thus, this study demonstrates that systemic RTX diminishes the thermal pain sensitivity by depletion of unmyelinated afferent neurons. The delayed tactile allodynia induced by RTX is likely attributable to damage to myelinated afferent fibers and their abnormal sprouting in lamina II of the spinal dorsal horn. These data provide new insights into the potential mechanisms of postherpetic neuralgia.
Key words: neuropathic pain; postherpetic neuralgia; capsaicin; VR1 receptor; TRPV channel; spinal cord dorsal horn; axonal sprouting
Copyright © 2003 Society for Neuroscience 0270-6474/03/2372911-09$05.00/0
This article has been cited by other articles:
H. Sun, D.-P. Li, S.-R. Chen, W. N. Hittelman, and H.-L. Pan
Sensing of Blood Pressure Increase by Transient Receptor Potential Vanilloid 1 Receptors on Baroreceptors
J. Pharmacol. Exp. Ther., December 1, 2009; 331(3): 851 - 859.
[Abstract] [Full Text] [PDF]
J. Sandkuhler
Models and Mechanisms of Hyperalgesia and Allodynia
Physiol Rev, April 1, 2009; 89(2): 707 - 758.
[Abstract] [Full Text] [PDF]
H.-Y. Zhou, S.-R. Chen, H. Chen, and H.-L. Pan
Sustained Inhibition of Neurotransmitter Release from Nontransient Receptor Potential Vanilloid Type 1-Expressing Primary Afferents by {micro}-Opioid Receptor Activation-Enkephalin in the Spinal Cord
J. Pharmacol. Exp. Ther., November 1, 2008; 327(2): 375 - 382.
[Abstract] [Full Text] [PDF]
H.-Y. Zhou, H.-M. Zhang, S.-R. Chen, and H.-L. Pan
Increased C-Fiber Nociceptive Input Potentiates Inhibitory Glycinergic Transmission in the Spinal Dorsal Horn
J. Pharmacol. Exp. Ther., March 1, 2008; 324(3): 1000 - 1010.
[Abstract] [Full Text] [PDF]
H.-Y. Zhou, H.-M. Zhang, S.-R. Chen, and H.-L. Pan
Increased Nociceptive Input Rapidly Modulates Spinal GABAergic Transmission Through Endogenously Released Glutamate
J Neurophysiol, January 1, 2007; 97(1): 871 - 882.
[Abstract] [Full Text] [PDF]
C. Qin, J. P. Farber, K. E. Miller, and R. D. Foreman
Responses of thoracic spinal neurons to activation and desensitization of cardiac TRPV1-containing afferents in rats
Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2006; 291(6): R1700 - R1707.
[Abstract] [Full Text] [PDF]
K. Obata, H. Katsura, J. Sakurai, K. Kobayashi, H. Yamanaka, Y. Dai, T. Fukuoka, and K. Noguchi
Suppression of the p75 Neurotrophin Receptor in Uninjured Sensory Neurons Reduces Neuropathic Pain after Nerve Injury.
J. Neurosci., November 15, 2006; 26(46): 11974 - 11986.
[Abstract] [Full Text] [PDF]
S.-R. Chen and H.-L. Pan
Loss of TRPV1-Expressing Sensory Neurons Reduces Spinal {micro} Opioid Receptors But Paradoxically Potentiates Opioid Analgesia
J Neurophysiol, May 1, 2006; 95(5): 3086 - 3096.
[Abstract] [Full Text] [PDF]
Z. Gao, O. Henig, V. Kehoe, L. I. Sinoway, and J. Li
Vanilloid type 1 receptor and the acid-sensing ion channel mediate acid phosphate activation of muscle afferent nerves in rats
J Appl Physiol, February 1, 2006; 100(2): 421 - 426.
[Abstract] [Full Text] [PDF]
Z.-Z. Wu, S.-R. Chen, and H.-L. Pan
Transient Receptor Potential Vanilloid Type 1 Activation Down-regulates Voltage-gated Calcium Channels through Calcium-dependent Calcineurin in Sensory Neurons
J. Biol. Chem., May 6, 2005; 280(18): 18142 - 18151.
[Abstract] [Full Text] [PDF]
Z.-Z. Wu, S.-R. Chen, and H.-L. Pan
Differential Sensitivity of N- and P/Q-Type Ca2+ Channel Currents to a {micro} Opioid in Isolectin B -Positive and -Negative Dorsal Root Ganglion Neurons
J. Pharmacol. Exp. Ther., December 1, 2004; 311(3): 939 - 947.
[Abstract] [Full Text] [PDF]
K. Obata, H. Yamanaka, K. Kobayashi, Y. Dai, T. Mizushima, H. Katsura, T. Fukuoka, A. Tokunaga, and K. Noguchi
Role of Mitogen-Activated Protein Kinase Activation in Injured and Intact Primary Afferent Neurons for Mechanical and Heat Hypersensitivity after Spinal Nerve Ligation
J. Neurosci., November 10, 2004; 24(45): 10211 - 10222.
[Abstract] [Full Text] [PDF]
D.-P. Li, S.-R. Chen, and H.-L. Pan
VR1 Receptor Activation Induces Glutamate Release and Postsynaptic Firing in the Paraventricular Nucleus
J Neurophysiol, September 1, 2004; 92(3): 1807 - 1816.
[Abstract] [Full Text] [PDF]
Y.-Z. Pan and H.-L. Pan
Primary Afferent Stimulation Differentially Potentiates Excitatory and Inhibitory Inputs to Spinal Lamina II Outer and Inner Neurons
J Neurophysiol, June 1, 2004; 91(6): 2413 - 2421.
[Abstract] [Full Text] [PDF]
M. R Zahner, D.-P. Li, S.-R. Chen, and H.-L. Pan
Cardiac vanilloid receptor 1-expressing afferent nerves and their role in the cardiogenic sympathetic reflex in rats
J. Physiol., September 1, 2003; 551(2): 515 - 523.
[Abstract] [Full Text] [PDF]
|
|
|
|
 |
|