Articles: neuropathic-pain.
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Insomnia, depression, and anxiety disorder are common problems for people with neuropathic pain. In this study, mild noxious heat stimuli increased the duration and number of spontaneous pain-like behaviors in sciatic nerve-ligated mice. We used functional magnetic resonance imaging to visualize the increased blood oxygenation level-dependent signal intensity in the anterior cingulate cortex (ACC) of mice with sciatic nerve ligation under mild noxious stimuli. ⋯ With the optogenetic tool channel rhodopsin-2 (ChR2), we demonstrated that selective photostimulation of these astrocytes in vivo triggered sleep disturbance. Taken together, these results suggest that neuropathic pain-like stimuli activated astrocytes in the ACC and decreased the extracellular concentration of GABA via an increase in the release of glutamate. Furthermore, these findings provide novel evidence that astrocytic activation in the ACC can mimic sleep disturbance in mice.
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Neuroscience letters · May 2014
Distinct role of tumor necrosis factor receptor subtypes 1 and 2 in the red nucleus in the development of neuropathic pain.
Previous studies have demonstrated that tumor necrosis factor-alpha (TNF-α) in the red nucleus (RN) plays a facilitated role in the development of neuropathic pain. Here, the protein levels and roles of two different TNF receptors, p55 type 1 (TNFR1) and p75 type 2 (TNFR2), in the RN of rats with spared nerve injury (SNI) were investigated. Immunohistochemistry demonstrated that both TNFR1 and TNFR2 were significantly increased in the RN of rats with SNI compared with sham-operated and normal rats. ⋯ Combined injection of anti-TNFR1-Ab and anti-TNFR2-Ab (500ng for each antibody) into the RN generated a relatively faster and longer analgesic effect compared with single using of anti-TNFR1-Ab or anti-TNFR2-Ab. These results support that TNF-α in the RN plays a crucial role in regulating neuropathic pain, and suggest that the algesic effect of TNF-α is transmitted through both TNFR1 and TNFR2. TNFR1 has equally important role in the early development and later maintenance of neuropathic pain, while TNFR2 is more inclined to play a role in the early development of neuropathic pain.
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Opiate analgesia in the spinal cord is impaired during neuropathic pain. We hypothesized that this is caused by a decrease in μ-opioid receptor inhibition of neurotransmitter release from primary afferents. To investigate this possibility, we measured substance P release in the spinal dorsal horn as neurokinin 1 receptor (NK1R) internalization in rats with chronic constriction injury (CCI) of the sciatic nerve. ⋯ In contrast, DAMGO still inhibited substance P release after inflammation of the hind paw with complete Freund's adjuvant and in naïve rats. This loss of inhibition was not due to μ-opioid receptor downregulation in primary afferents, because their colocalization with substance P was unchanged, both in dorsal root ganglion neurons and primary afferent fibers in the dorsal horn. In conclusion, nerve injury eliminates the inhibition of substance P release by μ-opioid receptors, probably by hindering their signaling mechanisms.
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The blood-nerve barrier (BNB) is a selectively permeable barrier that creates an immunologically and biochemically privileged space for peripheral axons and supporting cells. The breakdown of the BNB allows access of blood-borne (hematogenous) cells and molecules to the endoneurium to engage in the local inflammatory cascade. This process was examined in a mouse model of trauma-associated neuropathic pain. ⋯ These results demonstrate that blood-borne molecules may play a role in the generation of neuropathic pain, suggesting that pain may be driven from infection or injury, at a distance from the nervous system. Furthermore, the breakdown of the BNB in neuropathic conditions was exploited to permit the entry of analgesic molecules that typically cannot pass the BNB, such as ProToxin-II, a BNB-impermeable Nav1.7 inhibitor. Therapeutics utilizing this mechanism could have selective access to injured nerves over healthy tissues.