The European journal of neuroscience
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The nucleus accumbens (NAc) is a critical brain region for the rewarding effects of drugs of abuse. Brain-derived neurotrophic factor (BDNF) can facilitate stress- and drug-induced neuroadaptation in the mesocorticolimbic system. BDNF-containing projections to the NAc originate from the ventral tegmental area (VTA) and the prefrontal cortex, and BDNF release activates tropomyosin-related kinase B (TrkB). ⋯ NAc TrkB knockdown also prevented stress-induced elevation of BDNF and the glutamate receptor type 1 (GluA1) subunit of AMPA receptor in the VTA, as well as ΔFosB expression in the NAc. These findings indicated that BDNF-TrkB signaling in the NAc shell was required for social defeat stress-induced cross-sensitization. NAc TrkB-BDNF signaling also appeared to be involved in the regulation of GluA1 in the VTA, as well as in the NAc ΔFosB accumulation that could trigger cross-sensitization after social defeat stress.
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Electrical synapses formed by neuronal gap junctions composed of connexin36 (Cx36) are a common feature in mammalian brain circuitry, but less is known about their deployment in spinal cord. It has been reported based on connexin mRNA and/or protein detection that developing and/or mature motoneurons express a variety of connexins, including Cx26, Cx32, Cx36 and Cx43 in trigeminal motoneurons, Cx36, Cx37, Cx40, Cx43 and Cx45 in spinal motoneurons, and Cx32 in sexually dimorphic motoneurons. We re-examined the localization of these connexins during postnatal development and in adult rat and mouse using immunofluorescence labeling for each connexin. ⋯ By freeze-fracture replica immunolabeling, > 100 astrocyte gap junctions but no neuronal gap junctions were found based on immunogold labeling for Cx43, whereas 16 neuronal gap junctions at postnatal day (P)4, P7 and P18 were detected based on Cx36 labeling. Punctate labeling for Cx36 was localized to the somatic and dendritic surfaces of peripherin-positive motoneurons in the Mo5, motoneurons throughout the spinal cord, and sexually dimorphic motoneurons at lower lumbar levels. In studies of electrical synapses and electrical transmission between developing and between adult motoneurons, our results serve to focus attention on mediation of this transmission by gap junctions composed of Cx36.
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Pools of motoneurons in the lumbar spinal cord innervate the sexually dimorphic perineal musculature, and are themselves sexually dimorphic, showing differences in number and size between male and female rodents. In two of these pools, the dorsomedial nucleus (DMN) and the dorsolateral nucleus (DLN), dimorphic motoneurons are intermixed with non-dimorphic neurons innervating anal and external urethral sphincter muscles. As motoneurons in these nuclei are reportedly linked by gap junctions, we examined immunofluorescence labeling for the gap junction-forming protein connexin36 (Cx36) in male and female mice and rats. ⋯ In females, Cx36 labeling of puncta in the DLN was similar to that in males, but was sparse in the DMN. In enhanced green fluorescent protein (EGFP)-Cx36 transgenic mice, motoneurons in the DMN and DLN were intensely labeled for the EGFP reporter in males, but less so in females. The results indicate the presence of Cx36-containing gap junctions in the sexually dimorphic DMN and DLN of both male and female rodents, suggesting coupling of not only sexually dimorphic but also non-dimorphic motoneurons in these nuclei.
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Osteoarthritis is a degenerative joint disease associated with articular cartilage degradation. The major clinical outcome of osteoarthritis is a complex pain state that includes both nociceptive and neuropathic mechanisms. Currently, the therapeutic approaches for osteoarthritis are limited as no drugs are available to control the disease progression and the analgesic treatment has restricted efficacy. ⋯ The ubiquitous distribution of cannabinoid receptors, together with the physiological role of the endocannabinoid system in the regulation of pain, inflammation and even joint function further support the therapeutic interest of cannabinoids for osteoarthritis. However, limited clinical evidence has been provided to support this therapeutic use of cannabinoids, despite the promising preclinical data. This review summarizes the promising results that have been recently obtained in support of the therapeutic value of cannabinoids for osteoarthritis management.
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Review
The consequences of pain in early life: injury-induced plasticity in developing pain pathways.
Pain in infancy influences pain reactivity in later life, but how and why this occurs is poorly understood. Here we review the evidence for developmental plasticity of nociceptive pathways in animal models and discuss the peripheral and central mechanisms that underlie this plasticity. ⋯ Peripheral nerve sprouting and dorsal horn central sensitization, disinhibition and neuroimmune priming are discussed in relation to the increased pain and hyperalgesia, while altered descending pain control systems driven, in part, by changes in the stress/HPA axis are discussed in relation to the widespread hypoalgesia. Finally, it is proposed that the endocannabinoid system deserves further attention in the search for mechanisms underlying injury-induced changes in pain processing in infants and children.