• Misaki Matsumoto, Weijiao Xie, Lin Ma, and Hiroshi Ueda.
• Division of Molecular Pharmacology and Neuroscience, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8521, Japan. f2081@cc.nagasaki-u.ac.jp
• Mol Pain. 2008 Jan 1;4:25.

BackgroundWe have previously demonstrated that different spinal transmissions are involved in the nociceptive behavior caused by electrical stimulation of Abeta-, Adelta- or C-fibers using a Neurometer in naïve mice. In this study, we attempted to pharmacologically characterize the alteration in spinal transmission induced by partial sciatic nerve injury in terms of nociceptive behavior and phosphorylation of extracellular signal-regulated kinase (pERK) in the spinal dorsal horn.ResultsAbeta-fiber responses (2000-Hz), which were selectively blocked by the AMPA/kainate antagonist CNQX in naïve mice, were hypersensitized but blocked by the NMDA receptor antagonists MK-801 and AP-5 in injured mice in an electrical stimulation-induced paw withdrawal (EPW) test. Although Adelta-fiber responses (250-Hz) were also hypersensitized by nerve injury, there was no change in the pharmacological characteristics of Adelta-fiber responses through NMDA receptors. On the contrary, C-fiber responses (5-Hz) were hyposensitized by nerve injury. Moreover, Adelta- and C-, but not Abeta-fiber stimulations significantly increased the number of pERK-positive neurons in the superficial spinal dorsal horns of naïve mice, and corresponding antagonists used in the EPW test inhibited this increase. In mice with nerve injury, Abeta- as well as Adelta-fiber stimulations significantly increased the number of pERK-positive neurons in the superficial spinal dorsal horn, whereas C-fiber stimulation decreased this number. The nerve injury-specific pERK increase induced by Abeta-stimulation was inhibited by MK-801 and AP-5, but not by CNQX. However, Abeta- and Adelta-stimulations did not affect the number or size of pERK-positive neurons in the dorsal root ganglion, whereas C-fiber-stimulation selectively decreased the number of pERK-positive neurons.ConclusionThese results suggest that Abeta-fiber perception is newly transmitted to spinal neurons, which originally receive only Adelta- and C-fiber-mediated pain transmission, through NMDA receptor-mediated mechanisms, in animals with nerve injury. This pharmacological switch in Abeta-fiber spinal transmission could be a mechanism underlying neuropathic allodynia.

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