Pain
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Neurotrophin-3 (NT-3) is a target-derived neurotrophic factor that regulates sensory neuronal survival and growth. Here we report that NT-3 plays a critical permissive role in cutaneous sensory nerve sprouting that contributes to pain and sensitivity following skin wounding in young animals. ⋯ The requirement for NT-3 for sensory terminal sprouting in vivo is confirmed by the absence of wound-induced hyperinnervation in heterozygous transgenic mice (NT-3(+/-)lacZ). We conclude that upregulation of NT-3 in neonatally wounded skin is a critical factor mediating the sensory nerve sprouting that underlies hypersensitivity and pain following skin injury.
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The anterior cingulate cortex (ACC) has been shown to play an important role in pain-related perception and chronic pain. However, little is known about the molecular mechanisms involved. To address this issue, we analyzed excitatory synaptic transmission and long-term synaptic plasticity in layer II/III pyramidal neurons within the rostral ACC (rACC) from mice with bone cancer pain induced by intra-tibia implantation of osteolytic fibrosarcoma cells. ⋯ Western blot analysis revealed a significant decrease in the levels of NR1, NR2A, and NR2B subunits of NMDA receptors in the rACC under bone cancer pain condition. No significant changes in overall mRNA levels for any of the NMDA receptor subunits or calpain activity were observed in the rACC of tumor-bearing mice. These results indicate that tumor-induced injury or remodeling of primary afferent sensory nerve fibers that innervate the tumor-bearing bone may cause a persistent decrease in NMDA receptor expression in rACC neurons, resulting in a loss of LTD induction, thereby leading to long-term alterations of rACC activity and creating exaggerated pain behaviors.