The Role Of Peripheral Group â…¢ MGluRs In Spinal Astrocytes Activation And Long-term Hyperalgesia Induced By CFA

Injection of complete Freund's adjuvant (CFA) to the hind paw of the rat is a widely used animal model of chronic inflammatory pain, after CFA administration, animal will display a hypersensitivity to thermal and mechanic stimuli, which can be characterized by a rapid reduction in paw withdrawal latency to thermal and mechanic stimuli. The thermal hyperalgesia peaks in 2 to 6 hr and persists more than 2 wks after peripheral injection of CFA.Recently, spinal astrocytes and microglia have been recognized as potential active participants in the initiation and maintenance of hyperalgesia. In this processes, microglial activation preceded astrocytic activation following peripheral inflammation, supporting a role of microglia in the initiation phase and astrocytes in maintaining long-term hyperalgesia (LTH). Glutamate is one of the predominant excitatory neurotransmitters. Activation of GluRs including iGluRs and mGluRs mediate nociceptive processing in both peripheral and central sensitization. Previous studies demonstrated that peripheral group III mGluRs play a critical role in the acute inflammatory pain induced by hindpaw administration of Formalin. Recently, studies showed that spinal glia express group III mGluRs.In the present study, CFA pain model was employed in which observation of nociceptive behavior in response of thermal stimuli, and immunohistochemical examination of activated marker of spinal astrocytes (GFAP) were carried out, combined with peripheral administration of L-SOP, an agonist of group III mGluRs, to determine the role of peripheral group III mGluRs in the spinal astrocytes activation and long-term hyperalgesia induced by CFA.Experiments were performed on adult male Sprague–Dawley rats with two parts of observations, behavioral examination and immunohistochamical assay. Sixty rats were divided into two groups, the first group or Pre-CFA treated group, L-SOP (250nmol, 25μL, Tocris) was injected into the plantar of the left hind paw 15 min prior to CFA injection and repeat the administration 1, 2, 3 and 4 days after CFA injection. The contralateral right hind paw of the rat received same volume of saline; the second group or Post-CFA treated group, L-SOP was injected into the plantar of the left hind paw 4 days after CFA injection and continued for another four days. The contralateral right hind paw of the same rat received same volume of saline. The nociceptive responses to thermal stimuli named paw withdraw latence was tested at 1d before CFA injection as a control and at 8h, 1d, 4d, 8d, and 14d post CFA injection, respectively. Rats...