Pain mechanismGroup II metabotropic glutamate receptor activation attenuates peripheral sensitization in inflammatory states
Section snippets
Experimental procedures
All experiments were approved by the University Animal Care and Use Committee and followed the IASP guidelines for the ethical care and use of laboratory animals (Zimmermann, 1983). Steps were taken to minimize both the number of animals and their discomfort. All rats were male, Sprague–Dawley (250–300 g) obtained from Harlan, Indianapolis, IN, USA.
Group II mGluR modulation of mechanical and thermal sensitivity
Intraplantar injection of 0.1 μM or 100 μM APDC in normal rats did not affect baseline thermal sensitivity, inducing no change in PWL compared with vehicle over the subsequent 40 min testing period (Fig. 1A). Similarly, intraplantar injection of either 0.1 μM or 100 μM APDC did not affect mechanical sensitivity, inducing no change in PWT compared with vehicle (Fig. 1B). The results suggest that APDC in this range does not modulate behavioral responses to acute thermal or mechanical stimulation
Discussion
These studies demonstrate several key aspects of peripheral Group II mGluR function. Activation of peripheral Group II mGluRs 1) does not depress nociceptive behavioral responses or nociceptor activity in the non-sensitized state (i.e. following brief nociceptive mechanical or thermal stimulation), 2) can depress these responses when the nociceptors are sensitized by inflammation, 3) can produce an inhibitory effect through local receptor activation that can be blocked by a local Group II
Conclusions
The results presented here demonstrate that Group II activation has no effect on normal (non-sensitized) nociceptor function. In contrast, when conditions arise where CMH nociceptors are sensitized by inflammatory mediators, activation of peripheral Group II mGluRs can dramatically reduce evoked nociceptive behaviors, and importantly, can effectively inhibit inflammatory mediator-induced excitation and sensitization, indicating that Group II mGluR activation is anti-hyperalgesic. Group II
Acknowledgments
The authors would like to thank Ms. Lyn Schilling for her assistance in preparing this manuscript. This work was supported by NIH grants NS27910, NS40700 and NS54765 to S.M.C.
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