Significance of medial preoptic area among the subcortical and cortical areas that are related to pain regulation in the rats with stress-induced hyperalgesia.

Psychophysical stresses frequently increase sensitivity and response to pain, which is termed stress-induced hyperalgesia (SIH). However, the mechanism remains unknown. The subcortical areas such as medial preoptic area (MPO), dorsomedial nucleus of the hypothalamus (DMH), basolateral (BLA) and central nuclei of the amygdala (CeA), and the cortical areas such as insular (IC) and anterior cingulate cortices (ACC) play an important role in pain control via the descending pain modulatory system. In the present study we examined the expression of phosphorylated -cAMP-response element binding protein (pCREB) and the acetylation of histone H3 in these subcortical and cortical areas after repeated restraint stress to reveal changes in the subcortical and cortical areas that affect the function of descending pain modulatory system in the rats with SIH. The repeated restraint stress for 3 weeks induced a decrease in mechanical threshold in the rat hindpaw, an increase in the expression of pCREB in the MPO and an increase in the acetylation of histone H3 in the MPO, BLA and IC. The MPO was the only area that showed an increase in both the expression of pCREB and the acetylation of histone H3 among these examined areas after the repeated restraint stress. Furthermore, the number of pCREB-IR or acetylated histone H3-IR cells in the MPO was negatively correlated with the mechanical threshold. Together, our data represent the importance of the MPO among the subcortical and cortical areas that control descending pain modulatory system under the condition of SIH.

Attenuation of pCREB and Egr1 expression in the insular and anterior cingulate cortices associated with enhancement of CFA-evoked mechanical hypersensitivity after repeated forced swim stress.

The perception and response to pain are severely impacted by exposure to stressors. In some animal models, stress increases pain sensitivity, which is termed stress-induced hyperalgesia (SIH). The insular cortex (IC) and anterior cingulate cortex (ACC), which are typically activated by noxious stimuli, affect pain perception through the descending pain modulatory system. In the present study, we examined the expression of phospho-cAMP response element-binding protein (pCREB) and early growth response 1 (Egr1) in the IC and ACC at 3h (the acute phase of peripheral tissue inflammation) after complete Freund's adjuvant (CFA) injection in naïve rats and rats preconditioned with forced swim stress (FS) to clarify the effect of FS, a stressor, on cortical cell activities in the rats showing SIH induced by FS. The CFA injection into the hindpaw induced mechanical hypersensitivity and increased the expression of the pCREB and Egr1 in the IC and ACC at 3h after the injection. FS (day 1, 10min; days 2-3, 20min) prior to the CFA injection enhanced the CFA-induced mechanical hypersensitivity and attenuated the increase in the expression of pCREB and Egr1 in the IC and ACC. These findings suggested that FS modulates the CFA injection-induced neuroplasticity in the IC and ACC to enhance the mechanical hypersensitivity. These findings are thought to signify stressor-induced dysfunction of the descending pain modulatory system.

Axonal projections of auditory cells with short and long response latencies in the medial geniculate nucleus: distinct topographies in the connection with the thalamic reticular nucleus.

The thalamic reticular nucleus (TRN) is a crucial anatomical node of thalamocortical connectivity for sensory processing. In the rat auditory system, we determined features of thalamic projections to the TRN, using juxtacellular recording and labeling techniques. Two types of auditory cells (short latency, SL, and long latency, LL), exhibiting unit discharges to noise burst stimuli (duration, 100 ms) with short (< 50 ms) and long (> 100 ms) response latencies, were obtained from the ventral division of the medial geniculate nucleus (MGV). Both SL and LL cells had a propensity to exhibit reverberatory discharges in response to sound stimuli. The primary discharges of SL cells were mostly single spikes while the non-primary discharges of SL cells and the whole discharges of LL cells were mostly burst spikes. SL cells sent topographic projections to the TRN along the dorsoventral and rostrocaudal neural axes while LL cells only along the rostrocaudal axis. As tonotopy-related cortical projections to the TRN are topographic primarily along the dorsoventral extent of the TRN and the MGV is tonotopically organized along the dorsoventral axis, SL cells, directly activated by ascending auditory inputs, may be closely involved in tonotopic thalamocortical connectivity. On the other hand, LL cells, which are suppressed by ascending inputs and could be driven to discharge by corticofugal inputs, are assumed to activate the TRN in a manner less related to tonotopic organization. There may exist heterogeneous projections from the MGV to the TRN, which, in conjunction with corticofugal connections, could constitute distinct channels of auditory processing.

Increase of galanin-like immunoreactivity in rat hypothalamic arcuate neurons after peripheral nerve injury.

Galanin and galanin receptors are widely distributed within the central nervous system, and may play important roles in pain signaling and modulation. In the present study, we examined the galanin immunoreactivity (IR) in the hypothalamus and the amygdala following peripheral nerve injury. Four weeks after the operation, the ipsilateral mechanical threshold in the spared nerve injury (SNI) group (0.87 +/- 0.33 g) was significantly lower than that in the sham group (12.53 +/- 3.41 g; P < 0.05). In the SNI group, the number of galanin-IR neurons per section in the arcuate nucleus (Arc) of the hypothalamus was 10.2 +/- 1.7, significantly higher than that in the sham group (5.6 +/- 1.0; P < 0.05). These data suggest that the galanin-ergic neurons in the Arc may be involved in the functional modulation of descending pain modulation system following peripheral nerve injury.