Brain research bulletin
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Brain research bulletin · Jan 2008
Evidence for suppression of electroacupuncture on spinal glial activation and behavioral hypersensitivity in a rat model of monoarthritis.
Our previous study demonstrated that single intrathecal (i.t.) application of fluorocitrate, a glial metabolic inhibitor, synergized electroacupuncture (EA) antagonizing behavioral hypersensitivity in complete Freund's adjuvant (CFA)-induced monoarthritic rat. To further investigate the relationship between spinal glial activation and EA analgesia, the present study examined the effects of multiple EA on spinal glial activation evoked by monoarthritis (MA). The results showed that (1) unilateral intra-articular injection of CFA produced a robust glial activation on the spinal cord, which was associated with the development and maintenance of behavioral hypersensitivity; (2) multiple EA stimulation of ipsilateral "Huantiao" (GB30) and "Yanglingquan" (GB34) acupoints or i.t. injection of fluorocitrate (1 nmol) significantly suppressed spinal glial activation; (3) inhibitory effects of EA on spinal glial activation and behavioral hypersensitivity were significantly enhanced when EA combined with fluorocitrate, indicating that disruption of glial function may potentiate EA analgesia in inflammatory pain states. These data suggested that analgesic effects of EA might be associated with its counter-regulation to spinal glial activation, and thereby provide a potential strategy for the treatment of arthritis.
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Brain research bulletin · Jan 2008
Long-lasting descending and transitory short-term spinal controls on deep spinal dorsal horn nociceptive-specific neurons in response to persistent nociception.
Under intact and spinalized conditions, we compared the responses of deep spinal dorsal horn (DH) nociceptive-specific (NS) and wide-dynamic range (WDR) neurons to subcutaneous bee venom (BV, 0.2 mg/50 microl)-induced persistent nociception. In contrast to the monophasic, long-lasting (34-81 min) WDR neuron responses in both intact and spinalized conditions, BV in NS neurons elicited short-term (<10 min) firing in intact, and long-term (>1 h) biphasic firing in spinalized rats. The BV-induced long-term biphasic NS neuron activities in spinalized condition consisted of a first, early phase (4-13 min) of firing occurred immediately after the BV injection, and a second phase of tonic firing that lasted for 28-74 min. ⋯ Using the neurokinin-1 (NK-1) receptor antagonist, L-703,606 we further found that only early (within 15 min) treatment with L-703,606 produced a significant inhibition of the enhanced mechanically evoked NS neuron responses in BV-induced nociception, suggesting a dynamic function of NK-1 receptor involvement for deep spinal NS neuron mediated central sensitisation. We conclude that deep spinal DH NS neurons are strictly governed by tonic inhibitory descending controls. As this descending inhibitory control either is absent or decays, deep spinal NS neurons may play a crucial role in the development of central sensitisation in pathological nociception, for instance in spinal cord injury-induced pathological pain.
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Brain research bulletin · Jan 2008
Voltage-gated sodium channel Nav1.1, Nav1.3 and beta1 subunit were up-regulated in the hippocampus of spontaneously epileptic rat.
The spontaneously epileptic rat (SER), a double mutant (zi/zi, tm/tm), exhibits both tonic convulsions and absence-like seizures from the age of 8 weeks. Since the first point mutation in the voltage-gated sodium channel (VGSC) beta(1) subunit in human generalized epilepsy with febrile seizures plus (GEFS+) was identified, more and more types of genetic epilepsy have been causally suggested to be related to gene changes in VGSC. However, there are no reports that can elucidate the effects of VGSC in SER. ⋯ In this study, the mRNA expressions of Na(v)1.1, Na(v)1.3 and beta(1) subunit in SERs hippocampus were significantly higher than those in control rats hippocampus by real-time RT-PCR; The protein distributions and expressions of Na(v)1.1, Na(v)1.3 and beta(1) subunit in SERs hippocampus were detected by immunofluorescence, immunohistochemistry and western blot, and the protein expressions of Na(v)1.1, Na(v)1.3 and beta(1) subunit were significantly increased. In conclusion, our study suggested for the first time that sodium channel Na(v)1.1, Na(v)1.3 and beta(1) subunit up-regulation at the mRNA and protein levels of SER hippocampus might contribute to the generation of epileptiform activity and underlie the observed seizure phenotype in SER. The results of this study may be of value in revealing components of the molecular mechanisms of hippocampal excitation that are related to genetic epilepsy.