Activation of extracellular signal-regulated protein kinase in the dorsal root ganglion following inflammation near the nerve cell body
Section snippets
Animals
A total of 145 male Sprague–Dawley rats weighing 200–250 g were used. All animal experimental procedures were approved by the Hyogo College of Medicine Committee on Animal Research and were performed in accordance with the National Institutes of Health guidelines on animal care. Every effort was undertaken to minimize the number of animals used and their discomfort.
Surgical procedures
All experimental procedures were done on rats that were deeply anesthetized with sodium pentobarbital (50 mg/kg body weight, i.p.).
Inflammation near the cell body produces mechanical hypersensitivity on the ipsilateral hindpaw
First, we studied the time course of neuropathic pain behavior in the sham and CFA groups of rats (Fig. 1A, B). Before surgery, rats rarely withdrew their paws from the innocuous mechanical stimuli applied to the plantar surface of the hindpaw. In all groups, the response frequency on the contralateral paw did not vary significantly from baseline values (data not shown). Rats in the CFA group responded to the von Frey filament on 40.0±9.3% and 35.0±8.2% of the trials on the ipsilateral side at
Discussion
The present study demonstrated the following new findings. (1) Inflammation near the DRG somata induced by CFA produced mechanical allodynia, but not thermal hyperalgesia, on the ipsilateral hindpaw for a short period and induced an increase in the phosphorylation of ERK, mainly in trkA-expressing small- and medium-size neurons. Intrathecal treatment with the trk inhibitor, K252a, suppressed the CFA-induced increase in ERK phosphorylation. (2) Inflammation near the DRG somata induced an
Acknowledgements
This work was supported in part by Grants-in-Aid for Scientific Research and Grant for Open Research Center in Hyogo College of Medicine, from the Japanese Ministry of Education, Science and Culture. We thank Yuki Obata, Nobumasa Ushio, and Kimiko Kobayashi for technical assistance. We thank Dr. D. A. Thomas for correcting the English usage.
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2012, Experimental NeurologyCitation Excerpt :Several lines of evidence have established that activation of ERK in the primary afferent pathway regulates sensory hypersensitivity following peripheral inflammation or nerve injury. For example, in response to noxious stimulation of the peripheral tissue or electrical stimulation to the peripheral nerve, ERK1/2 is activated in the spinal cord dorsal horn neurons (Ji et al., 2002; Qiao et al., 2008), and both ERK1/2 and ERK5 are demonstrated to be phosphorylated in the DRG (Obata et al., 2003, 2004; Qiao and Gulick, 2007). Intrathecal injection of MEK inhibitor U0126 or PD98059, which specifically attenuates ERK1/2 and ERK5 activities (Kamakura et al., 1999), has significantly alleviated pain behavior induced by inflammation to hind paw (Ji et al., 2002; Obata et al., 2003), viscera (Cruz et al., 2007; Galan et al., 2003; Lai et al., 2011) or joint (Schrader et al., 2006).