T-type calcium channels, but not Cav3.2, in the peripheral sensory afferents are involved in acute itch in mice.

T-type calcium channels are prominently expressed in primary nociceptive fibers and well characterized in pain processes. Although itch and pain share many similarities including primary sensory fibers, the function of T-type calcium channels on acute itch has not been explored. We investigated whether T-type calcium channels expressed within primary sensory fibers of mouse skin, especially Cav3.2 subtype, involve in chloroquine-, endothelin-1- and histamine-evoked acute itch using pharmacological, neuronal imaging and behavioral analyses. We found that pre-locally blocking three subtypes of T-type calcium channels in the peripheral afferents of skins, yielded an inhibition in acute itch or pain behaviors, while selectively blocking the Cav3.2 channel in the skin peripheral afferents only inhibited acute pain but not acute itch. These results suggest that T-type Cav3.1 or Cav3.3, but not Cav3.2 channel, have an important role in acute itch processing, and their distinctive roles in modulating acute itch are worthy of further investigation.

Expression patterns of T-type Cav3.2 channel and insulin-like growth factor-1 receptor in dorsal root ganglion neurons of mice after sciatic nerve axotomy.

Substantial evidence indicates that T-type Cav3.2 channel and insulin-like growth factor-1 (IGF-1) contribute to pain hypersensitivity within primary sensory nerves. A recent study suggested that activation of IGF-1 receptor (IGF-1R) could increase Cav3.2 channel currents and further contribute to inflammatory pain sensitivity. However, the expression patterns of Cav3.2 and IGF-1R and their colocalization in dorsal root ganglion (DRG) in chronic neuropathic pain condition remain unknown. In this study, we explored expression patterns of Cav3.2, IGF-1R and their colocalization, and whether phenotypic switch occurs in a subpopulation of Cav3.2 or IGF-1R neurons in mouse DRGs after sciatic nerve axotomy with immunofluorescence, real-time reverse transcription-PCR, and western blot assays. We found that expressions of Cav3.2 and IGF-1R, and their colocalization were not increased in DRGs of mice following axotomy. In addition, Cav3.2 or IGF-1R subpopulation neurons did not acquire significant switch in expression phenotype after sciatic nerve axotomy. Our findings argue for an upregulation of Cav3.2 and IGF-1R expression in lumbar DRGs post-sciatic nerve axotomy and provided an insight for understanding the functions of peripheral afferent Cav3.2 channel and IGF-1/IGF-1R signaling in chronic neuropathic pain.

Colocalization of insulin-like growth factor-1 receptor and T type Cav3.2 channel in dorsal root ganglia in chronic inflammatory pain mouse model.

Insulin-like growth factor-1 (IGF-1) is a neurotrophic factor and plays important roles in the nervous system. Increasing evidence supports that IGF-1 contributes to pain hypersensitivity through its insulin-like growth factor-1 receptor (IGF-1R) by activating IGF-1R/Akt or MAPK signaling pathways, whereas T-type Cav3.2 channel can facilitate and amplify pain signals originating from the sensory periphery. A recent study showed that activated IGF-1R can increase T-type Cav3.2 channel currents and further activate the G protein-dependent PKCα pathway to contribute to inflammatory pain sensitivity. However, the colocalization of IGF-1R and Cav3.2 in mouse dorsal root ganglion (DRG) under chronic inflammatory pain conditions remains elusive. In this study, we investigated changes in the expression of IGF-1R and the Cav3.2 channel, and their colocalization in mouse DRGs in chronic inflammatory pain condition (induced by complete Freund's adjuvant intraplanter injection) using real-time RT-PCR and immunohistochemistry approaches to confirm that Cav3.2 channel can mediate pain facilitation following IGF-1/IGF-1R signaling. We found that IGF-1R was expressed extensively in DRG neurons including small-, medium-, and large-sized neurons, whereas Cav3.2 channel was expressed exclusively in small-sized DRG neurons of naive mice. Expression of Cav3.2, but not IGF-1R, and colocalization of Cav3.2 and IGF-1R were increased in lumbar (L)4-L6 primary sensory neurons in DRGs of mice in chronic inflammatory pain. Moreover, the increased colocalization of IGF-1R and Cav3.2 is exclusively localized in small- and medium-sized primary sensory neurons. Our findings provided morphological evidence that T-type Cav3.2 channel, at least partially, mediates the pain facilitation of IGF-1/IGF-1R signaling in chronic inflammatory pain condition.

Propofol Affects Different Human Brain Regions Depending on Depth of Sedation(△).

OBJECTIVE: To investigate the effect of propofol on brain regions at different sedation levels and the association between changes in brain region activity and loss of consciousness using blood oxygen level-dependent functional magnetic resonance imaging (BOLD-fMRI) and bispectral index (BIS) monitoring. METHODS: Forty-eight participants were enrolled at Peking Union Medical College Hospital from October 2011 to March 2012 and randomly assigned to a mild or a deep sedation group using computer- generated random numbers. Preliminary tests were performed a week prior to scanning to determine target effect site concentrations based on BIS and concomitant Observer's Assessment of Alertness/Sedation scores while under propofol. Within one week of the preliminary tests where propofol dose-response was established, BOLD-fMRI was conducted to examine brain activation with the subject awake, and with propofol infusion at the sedation level. RESULTS: Mild propofol sedation inhibited left inferior parietal lobe activation. Deep sedation inhibited activation of the left insula, left superior temporal gyrus, and right middle temporal gyrus. Compared with mild sedation, deep propofol sedation inhibited activation of the left thalamus, precentral gyrus, anterior cingulate, and right basal nuclei. CONCLUSION: Mild and deep propofol sedation are associated with inhibition of different brain regions, possibly explaining differences in the respective loss of consciousness processes.

Effects of propofol on brain activation in respond to mechanical stimuli.

OBJECTIVE: To observe the effects of different concentrations of propofol on brain regions activated by mechanical stimuli, and then to investigate the analgesic effect of propofol. METHODS: Twenty healthy male volunteers were randomly divided into two groups: light anesthesia group (group L) (BIS 60-80) and deep anesthesia group (group D)(BIS 40-60). Propofol was administrated by target controlled infusion system in pilot study. The target effect site concentration (ESC) of propofol was defined as the average of the ESC from BIS 80 to 60 or BIS 60 to 40 in group L or group D respectively. Mechanical stimuli were applied using von Frey filaments at the center of the left foot, and the pain threshold and VAS scores were evaluated. fMRI examinations were taken 1 week after pilot study with the following sequences: structure imaging+ functional imaging: functional imaging=stimulus sequence+propofol sequence, in which the stimulus sequence was 6 × (20 s on + 20 s off). This sequence was repeated after propofol sequence. RESULTS: As shown by fMRI, in group L, active brain regions of (the second stimulation-the first stimulation, P2-P1) were seen in cingulate gyrus, thalamus, and cerebellum, while active brain regions of (P1-P2) were seen in temporal lobe, frontal gyrus, and occipital lobe. In group D, the active brain region of (P2-P1) was only seen in cerebellum, while active brain regions of (P1-P2) were seen in cingulate gyrus and thalamus. Active brain regions of (deep-low) with propofol infusion in response to vFFs stimulation were observed in cerebellum. CONCLUSIONS: Propofol at different concentrations has different effect on the activation of brain regions. It may exert its analgesic effect via different mechanisms.

[Pharmacokinetic and pharmacodynamic characteristics of the domestic sevoflurane for transabdominal hysterectomy].

OBJECTIVE: To evaluate the clinical efficacy of domestic sevoflurane by comparing the pharmacokinetic and pharmacodynamic characteristics of domestic sevoflurane and an imported product. METHODS: Eighty patients undergoing general anesthesia for transabdominal hysterectomy were equally randomized into domestic sevoflurane group and imported sevoflurane group. The following data were recorded and compared: vital signs; change of sevoflurane concentrations in the induction period and recovery period; the time when inhaled sevoflurane concentration reached half of the pre-set concentration of the vaporizer; the time when the end-tidal sevoflurane concentration reached half of the pre-set concentration of the vaporizer; the time when the end-tidal sevoflurane concentration reached half of inhaled sevoflurane concentration; the time of the end-tidal sevoflurane concentration reached 0. 8 MAC in the induction period; the recovery time; the extubation time; and time to recovery of consciousness. RESULTS: The general conditions of the two groups were not significantly different. The pharmacokinetic and pharmacodynamic parameters at the intra-operative time points as well as the minimal alveolar concentration, the inspired and end-tidal sevoflurane concentrations, and the time to recovery of consciousness also showed no significant differences between the two groups. CONCLUSION: The domestic sevoflurane has similar pharmacokinetic and pharmacodynamic characteristics as the imported products. It can serve as a cost-effective product for transabdominal hysterectomy.

[Comparison of cerebral state index and bispectral index accuracies in sedation monitoring during target control infusion of midazolam].

OBJECTIVE: To compare the accuracies of cerebral state index (CSI) and bispectral index (BIS) in sedation monitoring during target control infusion of midazolam. METHODS: Twenty informed adult male volunteers were intravenously administered with midazolam through plasma target control infusion from 30ng/ml (in increments of 10ng/ml every time) until they became unresponsive to tactile stimulation (i. e., mild prodding or shaking). The BIS and CSI were continuously recorded simultaneously. Sedation was assessed using the Observers' Assessment of Alertness/Sedation (OAA/S) scale at each time when Ct equaled to Ce. The electroencephalogram (EEG) parameters were correlated with the OAA/S scores using nonparametric Spearman's correlation analysis. The prediction probabilities were calculated at the points of lost of verbal contact (LVC) and lost of responses to stimulus (LOR). BIS05, BIS50, BIS95, and CSI05, CSI50, CSI95 were also calculated for LVC and LOR. RESULTS: BIS and CSI were well correlation with OAA/S scales during both the onset and recovery phases. When the sedation level increased, BIS and CSI progressively decreased. The prediction probabilities of BIS and CSI were 84%, 74% for LVC and 79%, 68% for LOR, while the BIS05, BIS50, and BIS95 as well as CSI05, CSI50, and CSI95 were 85.5, 60.6, and 35.7 (for BISs) and 82.2, 65.2, and 30.3 (for CSIs) at the point of LVC and 79.7, 47.6, and 15.6 (for BISs) and 75.9, 43.4, and 11 (for CSIs) at the point of LOR. CONCLUSIONS: Both CSI and BIS seem to be useful parameters for assessing midazolam-induced sedation. BIS is superior in the prediction of LVC and LOR.