Neuroreport
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To investigate the role of Group I mGluRs in allodynia and hyperalgesia, we examined the behavioural responses of rats to noxious and non-noxious mechanical and thermal stimuli following intrathecal (i.t.) treatment (25 nmol) with the selective mGluR1/5 agonist, (RS)-dihydroxyphenylglycine ((RS)-DHPG). (RS)-DHPG administration produced a persistent decrease in response latency on a 48 degrees C hotplate, a reduction in the 50% response threshold to von Frey hairs, and an increase in responses to a tail pinch. These data suggest that activation of spinal mGluR1/5 receptors plays a role in the development of persistent allodynia and hyperalgesia associated with tissue or nerve injury.
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It has been suggested that hyperexcitability in dorsal root ganglion (DRG) neurons due to altered sodium channel expression contributes to some chronic pain syndromes. To understand the role of the voltage-gated sodium channel alpha-SNS in inflammatory pain, we investigated the expression of alpha-SNS mRNA and tetrodotoxin-resistant (TTX-R) sodium current in small DRG neurons, which include nociceptive cells, following injection of carrageenan into the hind paw of the rat using in situ hybridization and patch-clamp recording. alpha-SNS mRNA expression in DRG neurons projecting to the inflamed limb was significantly increased 4 days following carrageenan injection, compared with DRG neurons from the contralateral side or naive (uninjected) rats (mean +/- s.d. optical density ratio: ipsilateral/contralateral, 1.77 +/- 0.17; ipsilateral/naive, 1.88 +/- 0.36). ⋯ The TTX-R current density was also significantly increased. These results demonstrate the increased expression of alpha-SNS sodium channels in small DRG neurons following injection of carrageenan into their projection field, and suggest that alpha-SNS is involved in the development of hyperexcitability associated with inflammation.