Pain
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Neuropathic pain resulting from spinal hemisection or selective spinal nerve ligation is characterized by an increase in membrane-bound tumor necrosis factor-alpha (mTNFα) in spinal microglia without detectable release of soluble TNFα (sTNFα). In tissue culture, we showed that a full-length transmembrane cleavage-resistant TNFα (CRTNFα) construct can act through cell-cell contact to activate neighboring microglia. We undertook the current study to test the hypothesis that mTNFα expressed in microglia might also affect the phenotype of primary sensory afferents, by determining the effect of CRTNFα expressed from COS-7 cells on gene expression in primary dorsal root ganglia (DRG) neurons. ⋯ Exposure to sTNFα produced an increase only in CCL2 expression and release. Treatment of the cells with an siRNA against tumor necrosis factor receptor 2 (TNFR2) significantly reduced CRTNFα-induced gene expression changes in DRG neurons, whereas administration of CCR2 inhibitor had no significant effect on CRTNFα-induced increase in gene expression and CCL2 release in DRG neurons. Taken together, the results of this study suggest that mTNFα expressed in spinal microglia can facilitate pain signaling by up-regulating the expression of cation channels and CCL2 in DRG neurons in a TNFR2-dependent manner.
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Dysmenorrhea is the most prevalent gynecological disorder in women of child-bearing age. Dysmenorrhea is associated with central sensitization and functional and structural changes in the brain. Our recent brain morphometry study disclosed that dysmenorrhea is associated with trait-related abnormal gray matter (GM) changes, even in the absence of menstrual pain, indicating that the adolescent brain is vulnerable to menstrual pain. ⋯ Volume changes in regions involved in the regulation of endocrine function and pain transmission correlated with the menstrual pain experience scores. Our results demonstrated that short-lasting cyclic menstrual pain is associated not only with trait-related but also rapid state-related structural alterations in the brain. Considering the high prevalence rate of menstrual pain, these findings mandate a great demand to revisit dysmenorrhea with regard to its impact on the brain and other clinical pain conditions.
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The period between migraine attacks is characterized by paradoxical responses to repetitive sensory and transcranial magnetic stimulation (TMS). Abnormal long-term cortical functional plasticity may play a role and can be assessed experimentally by paired associative stimulation (PAS), in which somatosensory peripheral nerve stimuli are followed by TMS of the motor cortex. Changes in motor-evoked potential (MEP) amplitudes were recorded in 16 migraine without aura patients (MO) and 15 healthy volunteers (HV) before and after PAS, which consisted of 90 peripheral electrical right ulnar nerve stimulations and subsequent TMS pulses over the first dorsal interosseous (FDI) muscle activation site with a delay of 10 ms (excitability depressing) or 25 ms (excitability enhancing). ⋯ Although in HV MEP amplitudes were significantly potentiated (+55.1) after PAS25, only a slight, nonsignificant increase was observed in MO (+18.8%). In the control experiment, performed on 8 subjects pooled together, Pearson's correlation showed an inverse relationship between the percentage of MEP amplitude changes after PAS10 and early HFO amplitudes (r=-0.81; P=.01). Because we observed that the more deficient the long-term PAS-induced change, the more the thalamocortical activation decreased, we hypothesize that the abnormalities in long-term cortical plasticity observed in the interictal period between migraine episodes could be due to altered thalamic control.
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Children born very preterm (≤ 32 weeks gestation) exhibit greater internalizing (anxious/depressed) behaviors compared to term-born peers as early as 2 years corrected age (CA); however, the role of early stress in the etiology of internalizing problems in preterm children remains unknown. Therefore, we examined the relationship between neonatal pain and internalizing behavior at 18 months CA in children born very preterm and examined whether parent behavior and stress moderated this relationship. Participants were 145 children (96 very preterm, 49 full term) assessed at 18 months CA. ⋯ Parent Sensitivity and Nonhostility moderated the relationship between neonatal pain and Internalizing behavior (all P<.05); higher parent education (P<.03), lower Parenting Stress (P=.001), and fewer children in the home (P<.01) were associated with lower Internalizing behavior in very preterm children, after adjusting for neonatal medical confounders, gender, and child cognitive ability (all P>.05). Parent Emotional Availability and stress were not associated with Internalizing behaviors in full-term control children. Positive parent interaction and lower stress appears to ameliorate negative effects of neonatal pain on stress-sensitive behaviors in this vulnerable population.