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J Neurophysiol (May 17, 2006). doi:10.1152/jn.00377.2006
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Submitted on April 10, 2006
Accepted on May 12, 2006

GABAA receptor blockade reverses the injury-induced sensitization of Nociceptor Specific (NS) neurons in the spinal dorsal horn of the rat

Esther Garcia-Nicas1, Jennifer M A Laird2, and Fernando Cervero3*

1 Anatomy, Histology and Neuroscience, Universidad Autonoma, Madrid, Madrid, Spain
2 Bioscience, AstraZeneca R&D Montreal, Montreal, Canada
3 Anesthesia Research, McGill University, Montreal, Canada

* To whom correspondence should be addressed. E-mail: fernando.cervero{at}mcgill.ca.

Single unit electrical activity has been recorded from 80 Nociceptor Specific (NS) neurons in the dorsal horn of the lumbar spinal cord of pentobarbital anesthetized rats. Their responses to low and high intensity mechanical stimulation of their receptive fields (RFs) were recorded before and after the application of irritant agents (Capsaicin (CAP) or Mustard oil (MO)) to the RF. Before the applications of the irritants the neurons responded only to high intensity stimuli, but after this procedure 20 of 28 neurons tested were sensitized, i.e. gave increased responses to high intensity stimuli and showed novel responses to low intensity mechanical stimulation as well as an A{beta}-fiber afferent drive. CAP was more likely to induce sensitization than MO and the majority of sensitized neurons were located in the superficial dorsal horn. No relationship was found between the magnitude of the response to the sensitizing agent and the presence or absence of sensitization. Cumulative doses of two GABAA receptor antagonists, picrotoxin and bicuculline were administered systemically or applied directly over the spinal cord. The GABAA antagonists reversed the sensitization of the neurons by reducing the novel low threshold responses. These results show that NS neurons in the spinal dorsal horn can be sensitized by a sustained afferent discharge in peripheral nociceptors and that this sensitization can be reduced or reversed by low doses of GABAA receptor antagonists. This provides evidence for a mechanism in which an enhanced GABA-ergic transmission can lead to hyperexcitability and sensitization of NS neurons in the dorsal horn.




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Contribution of Substance P and Neurokinin A to the Differential Injury-Induced Thermal and Mechanical Responsiveness of Lamina I and V Neurons
J. Neurosci., January 24, 2007; 27(4): 762 - 770.
[Abstract] [Full Text] [PDF]




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