Brain research
-
Microglia in the spinal cord is evidenced to play a crucial role in neuropathic pain. Spinal P2X4 receptors (P2X4Rs), which are mainly expressed in microglia, have been investigated for their roles in neuropathic pain. Dexmedetomidine (DEX), a highly selective agonist of α2-adrenergic receptors, is clinically applied to sedation and analgesia. ⋯ Immunofluorescence assay indicated higher densities of microglia and P2X4Rs, which appeared yellow in colour, suggesting they were co-labelled. Intraperitoneal injections of DEX 40μg/kg for 14 consecutive days markedly reversed the SNI-induced decline of MWT; the activation of microglia was markedly inhibited; in addition, the protein expressions of P2X4Rs, p-p38-MAPK and BDNF were significantly downregulated. Thus, DEX could attenuate the neuropathic pain in SNI rats, of which the mechanism might be related to the down-expressed P2X4Rs, p-p38 and BDNF in microglia of spinal dorsal horn.
-
Dexmedetomidine, an α2 adrenoceptor agonist, provides neuroprotection against various cerebral ischemia models through its anti-apoptotic effects. Dexmedetomidine also improves paraplegia induced by intrathecal morphine after short-term spinal ischemia. However, there are no reports regarding dexmedetomidine׳s ability to provide neuroprotection solely against transient spinal ischemia. ⋯ Neurological deficit scores in the dexmedetomidine-treated rats were significantly lower than the scores in the control group at 24 and 48 h after ischemia (P<0.05). The number of viable motor nerve cells was significantly larger in the dexmedetomidine-treated rats than in the control rats (P<0.05), but the number of motor nerve cells in the dexmedetomidine group was significantly smaller than the sham group. Our results indicate that the continuous administration of dexmedetomidine improves neurological and histological outcomes 48 h after transient spinal ischemia in rats.
-
Estrogens and prolactin share important target tissues, including the gonads, brain, liver, kidneys and some types of cancer cells. Herein, we sought anatomical and functional evidence of possible crosstalk between prolactin and estrogens in the mouse brain. First, we determined the distribution of prolactin-responsive neurons that express the estrogen receptor α (ERα). ⋯ In addition, we performed hypothalamic gene expression analyses to determine possible post-ovariectomy changes in components of prolactin signaling. We observed no significant changes in the mRNA expression of prolactin receptor, STAT5a or STAT5b. In summary, sex hormones exert a permissive role in maintaining the brain's prolactin sensitivity, most likely through post-transcriptional mechanisms.
-
Inflammasomes are molecular platforms that upon activation by cellular infection or stress trigger the maturation of proinflammatory cytokines such as interleukin (IL)-1β to engage innate immune defenses. Increased production of IL-1β in pain and inflammation such as headache is well documented. However, limited evidence addresses the participation of inflammasomes in inflammatory pain. ⋯ Immunohistochemistry revealed that both NALP3 inflammasome and IL-1β immunoreactivity were existed mainly in small to medium-sized C-type neurons and increased over time, with intense cytoplasmic staining after 3 days of dural inflammation. Overall, the present observation indicated that dural inflammation promoted assembly of the multiprotein NALP3 complex, activated caspase-1, and induced processing of IL-1β, which provides an indirect evidence of the participation of NALP3 inflammasome in the cascade of events involved in the genesis of headaches by promoting IL-1β maturation in the TG. This may contribute to strategies for headache control.
-
Several studies show the role of the basolateral amygdala (BLA) in drug-seeking, relapse and the brain׳s emotional systems. Several lines of evidence indicate a functional interaction between opioid and endogenous cannabinoid systems. In the present study, we investigated the role of intra-BLA cannabinoid CB1 receptors in the potentiation, acquisition and expression of morphine-induced conditioned place preference (CPP). ⋯ Furthermore, microinjection of both AM251 (15, 45 and 90µmol) and WIN55,212-2 (1-4mmol), into the BLA had no effect on the expression of morphine (5mg/kg)-induced CPP. Our findings suggest that cannabinoid CB1 receptors in the BLA are involved in the development of reward-related behaviors and they can potentiate the rewarding effects of morphine. It seems that the glutamatergic projection from the BLA to the nucleus accumbens and reward-related learning in the hippocampus may be involved in the acquisition and expression of opioid reward-related behaviors in rats.