Effect of Training on the Ability of Nurses to Provide Humanistic Care: Systematic Review and Meta-analysis.

BACKGROUND: This article describes a systematic review evaluating the effectiveness of training on the humanistic care abilities of nurses. METHOD: The literature search was conducted in electronic databases to identify studies that evaluated the effect of training on the humanistic care abilities of nurses. Study selection was based on precise eligibility criteria. After the systematic review, a meta-analysis of standardized mean differences (SMDs) between posttraining and pretraining humanistic care scale scores was performed to evaluate the effect of training. RESULTS: A total of 11 studies were included (624 nurse participants; 97% women; weighted average age = 38.4 years; 95% confidence interval (CI) [31.5, 45.4]). Training schedules varied and ranged from a full-day workshop to brief weekly sessions for up to 2 months. The training framework involved compassion and empathy communication in most of the included studies. Training improved the humanistic care scale scores of the participants (SMD = 1.171; 95% CI [0.626, 1.716]; p < .0001), whereas no significant change was seen in the scores of control subjects (SMD = 0.588; 95% CI [-0.536, 1.713]; p = .305). The effect of training was observable for up to 1 year, although few studies carried out follow-up evaluations. CONCLUSION: Training has the potential to improve the humanistic care abilities of nurses. [J Contin Educ Nurs. 2023;54(9):430-436.].

[Spinal serotonergic receptor is involved in descending inhibition of cardiac nociception by the lateral reticular nucleus in rats].

OBJECTIVE: To investigate the role of the lateral reticular nucleus (LRN) in descending inhibition of cardiac nociception in rats and the involvement of spinal serotonergic receptors in the descending inhibition. METHODS: Male SD rats were randomly divided into 5 groups, namely bradykinin (BK) group, BK + glutamate group, BK + methysergide group, BK + glutamate + methysergide group, and BK + glutamate + vehicle group. The rats received glutamate microinjection in the LRN combined with the intrathecal injection of serotonergic receptor antagonist methysergide, and the changes in the cardiacsomatic motor reflex induced by intrapericardial BK injection were monitored by observing electromyogram (EMG) responses of the dorsal spinotrapezius muscle; c-Fos expression in the spinal dorsal horn was also tested. RESULTS: Compared with BK group, intra-LRN glutamate administration produced a significant inhibitory effect on intrapericardial BK-induced EMG in a dose-dependent manner, and c-Fos expression was significantly decreased in the spinal dorsal horn (P<0.05). Compared with BK + glutamate group, intrathecal administration of methysergide significantly attenuated the inhibitory effect of chemical stimulation of the LRN on intrapericardial BK-induced EMG and increased c-Fos expression in the spinal dorsal horn (P<0.05). Intrathecal administration of the vehicle did not produce any effect on EMG or c-Fos expression (P>0.05). CONCLUSION: The serotonergic receptors in the spinal cord are involved in LRN-mediated descending inhibition of cardiac nociception in rats.

Mechanism Underlying the Analgesic Effect Exerted by Endomorphin-1 in the rat Ventrolateral Periaqueductal Gray.

The ventrolateral periaqueductal gray (vlPAG) is an important brain area, in which 5-HTergic neurons play key roles in descending pain modulation. It has been proposed that opioid peptides within the vlPAG can excite the 5-HTergic neurons by alleviating tonic inhibition from GABAergic neurons, the so-called disinhibitory effect. However, no direct morphological evidence has been observed for the micro-circuitry among the opioid peptide-, GABA-, and 5-HT-immunoreactive (ir) profiles nor for the functional involvement of the opioid peptides in the intrinsic properties of GABAergic and 5-HTergic neurons. In the present study, through microscopic observation of triple-immunofluorescence, we firstly identified the circuitry among the endomorphin-1 (EM1, an endogenous ligand for the µ-opioid receptor)-ir terminals and GABA-ir and 5-HT-ir neurons within the rat vlPAG. The synaptic connections of these neurons were further confirmed by electron microscopy. Through the in vitro whole-cell patch-clamp method, we showed that EM1 has strong inhibitory effects on the spiking of GABAergic neurons. However, although the resting membrane potential was hyperpolarized, EM1 actually increased the firing of 5-HTergic neurons. More interestingly, EM1 strongly inhibited the excitatory input to GABAergic neurons, as well as the inhibitory input to 5-HTergic neurons. Finally, behavioral results showed that pretreatment with a GABA(A) receptor antagonist potentiated the analgesic effect of EM1, while treatment with a GABA(A) receptor agonist blocked its analgesic effect. In summary, by utilizing morphological and functional methods, we found that the analgesic effect of EM1 is largely dependent on its potent inhibition on the inhibitory inputs to 5-HTergic neurons, which overwhelms EM1's direct inhibitory effect on 5-HTergic neurons.

[The effect of electrical stimulation of nucleus tractus solitarius on cardiac nociception and its spinal cord mechanism in rat].

OBJECTIVE: Examine the effect of electrical stimulation of nucleus tractus solitaries (NTS) on cardiac-somatic motor reflex (CMR) that induced by intrapericardial administration of capsaicin to clarify the spinal cord mechanism of NTS involved in cardiac nociception in rat. METHODS: SD rats were randomly divided into electrical stimulation, control, yohimbine and naloxone group and treated with elecetrical stimulation NTS alone, or with intrathecal injection of vehicle, saline, norepinephrine a2 receptors antagonist (yohimbine), opioid receptor antagonist (naloxone) respectively. RESULTS: Electrical stimulation of NTS (10, 20, 50 MA), the CMR response deceased in an intensity-dependent manner (P<0.05); intrathecal injection of vehicle, saline had no effect on the inhibition effect of electrical stimulation (P>0.05); intrathecal injection of yohimbine (20 microg, 50 microg) or naloxone (50 microg, 100 microg), reversed the inhibition effect of electrical stimulation (P<0.05); intrathecal injection of low dose of naloxone, the inhibition effect of electrical stimulation was potentiated. CONCLUSION: Electrical stimulation of NTS has inhibition effect on cardiac nociception, norepinephrine alpha2 receptors and opioid receptor in spinal cord involved in this descending inhibition, low dose of naloxone has synergetic effect with descending inhibition.

The excitatory synaptic transmission of the nucleus of solitary tract was potentiated by chronic myocardial infarction in rats.

Angina pectoris is a common clinical symptom that often results from myocardial infarction. One typical characteristic of angina pectoris is that the pain does not match the severity of the myocardial ischemia. One possible explanation is that the intensity of cardiac nociceptive information could be dynamically regulated by certain brain areas. As an important nucleus for processing cardiac nociception, the nucleus of the solitary tract (NTS) has been studied to some extent. However, until now, the morphological and functional involvement of the NTS in chronic myocardial infarction (CMI) has remained unknown. In the present study, by exploring left anterior descending coronary artery ligation surgery, we found that the number of synaptophysin-immunoreactive puncta and Fos-immunoreactive neurons in the rat NTS two weeks after ligation surgery increased significantly. Excitatory pre- and postsynaptic transmission was potentiated. A bath application of a Ca2+ channel inhibitor GABApentin and Ca2+ permeable AMPA receptor antagonist NASPM could reverse the potentiated pre- and postsynaptic transmission, respectively. Meanwhile, rats with CMI showed significantly increased visceral pain behaviors. Microinjection of GABApentin or NASPM into the NTS decreased the CMI-induced visceral pain behaviors. In sum, our results suggest that the NTS is an important area for the process of cardiac afference in chronic myocardial infarction condition.

MicroRNA-34a regulates cardiac fibrosis after myocardial infarction by targeting Smad4.

BACKGROUND: Although few microRNAs (miRNAs) have been involved in the regulation of post-ischemic cardiac fibrosis, the exact effect and underlying mechanism of miRNAs in cardiac fibrosis remains unclear. Here, we sought to investigate whether microRNA-34 (miR-34) plays a role in the pathogenic development of myocardial fibrosis. METHODS: The myocardial infarction (MI) mice model was induced and cardiac fibroblasts were cultured. Histological analyses, quantitative real-time polymerase chain reaction and Western blotting analysis were used. RESULTS: We found that the miR-34 cluster, especially miR-34a, was upregulated in the MI heart. In vivo, inhibition of miR-34a reduces the severity of experimental cardiac fibrosis in mice. TGF-ß1 increased miR-34a expression in cardiac fibroblasts. Overexpressing miR-34a levels increased the profibrogenic activity of TGF-ß1 in cardiac fibroblast, whereas inhibition miR-34a levels weakened the activity. Finally, we showed that miR-34a's underlying mechanism during cardiac fibrosis occurs through the targeting of Smad4 expression. CONCLUSIONS: Our findings provide evidence that miR-34a plays a critical role in the progression of cardiac tissue fibrosis by directly targeting Smad4, which suggests that miR-34a may be new marker for cardiac fibrosis progression and that inhibition of miR-34a may be a promising strategy in the treatment of cardiac fibrosis.

[The role of NMDA and NK1 receptors in cardiac nociceptive information transmissions in the spinal cords of rats].

OBJECTIVE: To determine the effects of NMDA and NK1 receptor agonist and antagonist on the EMG and the synaptic mechanism of nociceptive information transmissions in the spinal cords. METHODS: Male SD rats were randomly divided into seven groups, with intrathecal injection of the following chemicals respectively: control group (10 microL saline), NMDA group (0.147 microg/10 pL NMDA), MK801 group (6.8 microg/10 microL MK801), MK801+NMDA group (6.8 microg/10 pL MK801+0. 147 microg/10 pL NMDA), Sar-SP group (1.4 pg/10 microL Sar-SP), CP-96345 group (5 microg/10 pL CP-96345), and CP-96345+Sar-SP group (1.4 micro/10 microL Sar-SP+5 microg/10 microL CP-96345). A cardiac pain model in rats through intrapericardial injection of capsaicin was established. Intrapericardial injection of capsaicin was given to the rats 10 min after intrathecal injection of the tested chemicals. The spinotrapezius electromyography (EMG) activities as an index of cardiac-somatic motor reflex were recorded simultaneously. RESULTS: Compared with the pre-test controls (100%), saline did not make a significant change to the capsaicin-evoked EMG response (96. 9% +/- 12. 5%, P>0. 05); NMDA agonist increased the capsaicin-evoked EMG response (185. 2% +/- 24. 4%) significantly (P<0. 05); neither MK801 nor a combined administration of MK801 and NMDA made a significant change to the capsaicin-evoked EMG response (106. 6% +/- 10. 2%, P> 0.05); Sar-SP increased the capsaicin-evoked EMG response (145. 6% 10. 1%) significantly (P<0. 05); whereas neither CP-96345 nor a combined administration of CP-96345 and Sar-SP made a significant change to the capsaicin-evoked EMG response (102. 2% +/- 8. 4%, P>0.05). CONCLUSION: NMDA and NK1 receptors may have participated in the transmissions of cardiac nociception information in the spinal cords of rats.

The role of α2 adrenoceptor in mediating noradrenaline action in the ventrolateral orbital cortex on allodynia following spared nerve injury.

The present study examined the role of α2 adrenoceptor in mediating noradrenaline action in the ventrolateral orbital cortex (VLO) on allodynia induced by spared nerve injury (SNI) in the rat. The mechanical paw withdrawal threshold (PWT) was measured using von-Frey filaments. Microinjection of noradrenaline (1, 2, 4 µg in 0.5 µl) into the VLO, contralateral to the site of nerve injury, reduced allodynia; PWT increased in a dose-dependent manner. Similar to noradrenaline, microinjection of selective α2 adrenoceptor agonist clonidine into the same VLO site also reduced allodynia, and was blocked by selective α2 adrenoceptor antagonist yohimbine. Furthermore, administration of γ-aminobutyric acid A (GABAA) receptor antagonist bicuculline or picrotoxin to the VLO significantly enhanced clonidine-induced inhibition of allodynia, while GABAA receptor agonist muscimol or THIP (2,5,6,7-retrahydroisoxazolo(5,4-c)pyridine-3-ol hydrochloride) attenuated clonidine-induced inhibition. These results suggest that noradrenaline acting in the VLO can potentially reduce allodynia induced by SNI, and this effect is mediated by α2 adrenoceptor. Moreover, GABAergic disinhibition may participate in α2 receptor mediating effects in neuropathic pain in the central nervous system.

Lateral reticular nucleus modulates the cardiosomatic reflex evoked by intrapericardial capsaicin in the rat.

The current study examined the role of the lateral reticular nucleus (LRN) in modulating the cardiosomatic reflex (CSR) induced by intrapericardial capsaicin in the anesthetized rat. Intrapericardial capsaicin was administered, and the CSR was monitored via electromyogram responses of the dorsal spinotrapezius muscle. Electrical stimulation of the LRN (10, 20 and 30 µA) depressed the CSR induced by intrapericardial capsaicin in an intensity-dependent manner. Microinjection of glutamate (4, 10, 20 and 40 nmol, in 0.2 µL) into the LRN replicated the effects of electrical stimulation. Furthermore, bilateral transections of the dorsolateral funiculus (DLF) decreased the LRN electrical stimulation-induced inhibition of the electromyogram responses. Intrathecal administration of the α2 -adrenergic receptor antagonist yohimbine or the serotonergic receptor antagonist methysergide significantly attenuated the LRN electrical stimulation-induced inhibition of the electromyogram responses. However, intrathecal application of the opioid receptor antagonist naloxone had no effect on the LRN electrical stimulation-induced inhibition. These results suggest that the LRN-DLF-spinal cord pathway is involved in descending inhibition of the CSR, and spinal α2 -adrenergic and serotonergic receptors participate in this descending inhibition.

Effects of soluble epoxide hydrolase inhibitor on the expression of fatty acid synthase in peripheral blood mononuclear cell in patients with acute coronary syndrome.

BACKGROUND: Researches have shown that soluble epoxide hydrolase inhibitors (sEHi) can protect against the development of atherosclerosis. Simultaneously, emerging evidences have implicated the association between fatty acid synthase (FAS) and acute coronary syndrome (ACS). We tested the hypothesis that sEHi could reduce the occurrence of ACS by regulating FAS. METHODS: Hospitalized ACS patients were selected as the ACS group (n = 65) while healthy normal subjects as the control group (n = 65). The blood levels of lipoproteins, fasting glucose, myocardial enzyme and high-sensitivity C-reactive protein (hs-CRP) were measured within 24 hours after admission. The peripheral blood mononuclear cells (PBMCs) were isolated and cultured. Trans-4-[4-(3-Adamantan-1-ylureido)cyclohexyloxy] benzoic acid (t-AUCB), a kind of sEHi, was then added to cells in various concentrations (0, 10, 50, 100 µmol/L). The expression of FAS, interleukin-6 (IL-6) mRNA and protein was detected by real-time PCR or Western blot, respectively. RESULTS: (1) Compared with the control group, the serum concentration of hs-CRP in the ACS group was increased (P<0.05). The expression of FAS, IL-6 mRNA and protein were significantly increased in PBMCs from the ACS group (all P<0.05). Moreover, the levels of FAS and IL-6 mRNA were positively correlated with the serum concentration of hs-CRP (r = 0.685, P<0.01; r = 0.715, P<0.01) respectively. (2) The expression of FAS, IL-6 mRNA and protein in PBMCs from the ACS group were dose-dependently inhibited by sEHi (all P<0.05). CONCLUSIONS: sEH inhibition regulated FAS and inhibited inflammation in cultured PBMCs from ACS patients, a mechanism that might prevent rupture of atherosclerotic lesions and protect against development of ACS.

[Effects of soluble epoxide hydrolase inhibitors on the expression of fatty acid synthase in peripheral blood mononuclear cell of patients and inflammatory response with acute coronary syndrome].

OBJECTIVE: To explore the effects of soluble epoxide hydrolase inhibitor (sEHi) on the expressions of fatty acid synthase (FASN) mRNA and protein in peripheral blood mononuclear cell (PBMCs) of patients with acute coronary syndrome (ACS) and to discuss the influences of sEHi in the regulated expression of FASN and inflammatory reaction. METHODS: The hospitalized ACS patients were selected as the ACS group (n = 35) while the healthy normal subjects as the control group (n = 30). The levels of lipoproteins, fasting blood glucose, myocardial enzyme and hs-CRP (high-sensitive C-reactive protein) were measured within 24 hours after admission. Meanwhile the PBMCs were separated and cultured and then t-AUCB was added in various concentrations (0, 1, 10, 50, 100 µmol/L). The cellular expressions of FASN, IL-6 mRNA and protein were detected by real-time PCR (polymerase chain reaction) and Western blot respectively. RESULTS: (1) The serum concentration of hs-CRP reached (5.6 ± 4.1) mg/L in the ACS group. And it was obviously higher than (1.3 ± 0.9) mg/L in the control group (P < 0.05). Compared with the control group, the expression levels of FASN, IL-6 mRNA and protein significantly increased in the ACS group (the relative expression amount of FASN mRNA: 1 vs 1.709 ± 0.272, FASN protein: 0.407 ± 0.065 vs 1.298 ± 0.087; relative expression amount of IL-6 mRNA: 1 vs 2.302 ± 0.200, IL-6 protein: 0.715 ± 0.058 vs 1.146 ± 0.083, P < 0.05). Moreover, the levels of FASN and IL-6 mRNA had positive correlations with the serum concentration of hs-CRP (r = 0.714, P < 0.01; r = 0.685, P < 0.01). (2) Compared with the control group (t-AUCB 0 µmol/L), 10, 50, 100 µmol/L t-AUCB had inhibited the expressions quantity of FASN, IL-6 mRNA and protein in PBMCs from the ACS group (P < 0.05). The relative expressions of FASN mRNA in t-AUCB 0, 10, 50, 100 µmol/L group were 1, 0.813 ± 0.038, 0.564 ± 0.100, 0.293 ± 0.043 respectively. The relative expressions of FASN protein in t-AUCB 0, 10, 50 and 100 µmol/L group were 0.957 ± 0.280, 0.935 ± 0.275, 0.855 ± 0.253, 0.685 ± 0.206 respectively. CONCLUSION: The inflammatory level increases obviously in the ACS group. And the expression level of FASN in PBMCs is closely correlated with the inflammatory level in the ACS patients; t-AUCB may prevent the ruptures of atherosclerotic lesions by regulating FASN and inhibiting inflammatory reactions in ACS patients.

Soluble epoxide hydrolase and ischemic cardiomyopathy.

BACKGROUND: The development of cardiovascular disease has been linked to lowered levels of epoxyeicosatrienoic acids (EETs) in the cardiovascular system. Ischemic cardiomyopathy is caused by atherosclerotic lesions in multi-coronary arteries especially diffusive lesions, which can lead to severe myocardial dysfunction, heart enlargement, heart failure, or arrhythmia, and so on. The EETs are metabolized by the soluble epoxide hydrolase (sEH) encoded by the EPHX2 gene that has several known polymorphisms. CONTENT: The EPHX2 gene polymorphism is associated with sEH catalytic activity and various cardiovascular diseases. sEH is distributed in a variety of organs and tissues and regulated by multiple factors. Research in the area has led to the presence of multiple powerful soluble epoxide hydrolase inhibitors (sEHIs), whose molecular structure and function has been optimized gradually. sEHIs increase EETs' concentration by inhibiting hydration of EETs into their corresponding vicinal diols. EETs are important signaling molecules and known as endothelium-derived hyperpolarizing factors (EDHF). sEHIs have been developed for their ability to prevent atherosclerosis, dilate the coronary artery, promote angiogenesis, ameliorate postischemic recovery of heart contractile function, decrease ischemia/reperfusion injury, modulate postischemic arrhythmia, and prevent heart failure. SUMMARY: sEH is one of the etiological factors of cardiovascular diseases, and plays an important role in the progression of myocardium ischemia. This indicates that sEHIs provide a new method for the prevention and treatment of ischemic cardiomyopathy.

[The effects of soluble epoxide hydrolase inhibitors on cholesterol efflux in adipocytes].

OBJECTIVE: To observe the effects of soluble epoxide hydrolase inhibitors tAUCB on cholesterol efflux in adipocytes. METHODS: 3T3-L1 preadipocytes were induced to differentiation and maturation. Cells were stimulated with 100 µg/L LPS after starved for 24 hours, then tAUCB in various concentrations (1, 10, 50, 100 µmol/L)were added for 24 h, or incubated with the peroxisome proliferator activated receptor gamma (PPARγ) antagonist GW9662 (5 µmol/L). 0 µmol/L tAUCB treated group was taken as empty control. After then, the mRNA expression of PPARγ and adenosine triphosphate binding cassette transporter A1(ABCA1) in cells were determined via realtime-PCR, the amounts of protein expression of PPARγ and ABCA1 in cells were detected by Western blot, the efflux rates of (3)H-cholesterol in cells were detected by means of liquid scintillation counter. RESULTS: tAUCB could dose-dependently increase the apolipoprotein A1 (apoA1)-mediated cholesterol efflux in adipocytes. After stimulated by 1, 10, 50, 100 µmol/L tAUCB, cholesterol efflux rates were (5.93 ± 0.66)%, (7.40 ± 0.43)%, (8.30 ± 0.34)%, (9.77 ± 0.42)% respectively, there were significant difference after treated by 10 - 100 µmol/L tAUCB compared with control (5.67 ± 0.17)% (P < 0.05).With the concentration of tAUCB increased, ABCA1, PPARγ mRNA and protein expression were also dose-dependently up-regulated. GW9662 could significantly inhibit the effects of tAUCB, and then reduce the cholesterol efflux and the expression of PPARγ and ABCA1 in adipocytes. CONCLUSIONS: tAUCB could up-regulate PPARγ expression in adipocytes, and promote the cholesterol efflux of adipocytes via apoA1-ABCA1 pathway, which might decrease the cellular cholesterol accumulation in adipocytes.

[Effects of soluble epoxide hydrolase inhibitors on lipid metabolism and secretive functions of adipocytes].

OBJECTIVE: To observe the effects of soluble epoxide hydrolase inhibitors-tAUCB on the uptake and degradation of ox-LDL in adipocytes. METHODS: 3T3-L1 preadipocytes were induced into differentiation and maturation. After a 24-hour starvation, the cells were stimulated with 100 ng/ml LPS and then tAUCB at various concentrations (0 - 100 µmol/L)were added for 24 h, or preincubated with the PPARγ (peroxisome proliferators activated receptor gamma) antagonist GW9662 (5 µmol/L). And the 0 µmol/L tAUCB-treated group was taken as the blank control group. Then the uptake and degradation of ox-LDL in cells were measured by radioligand assay. The mRNA expressions of PPARγ and CD36 were detected by real-time PCR (polymerase chain reaction). And the intracellular levels of protein expression of PPARγ and CD36 were detected by Western blot. While ADP and TNF-α in supernatant were detected by ELISA. RESULTS: tAUCB could dose-dependently increase the uptake and degradation of ox-LDL in adipocytes. When stimulated with 10, 50, 100 µmol/L tAUCB, the uptake levels of ox-LDL were (35.6 ± 1.1)ng/mg, (39.8 ± 1.6) ng/mg, (42.6 ± 1.4) ng/mg cell protein and the degradation levels of ox-LDL (2879 ± 54) ng/mg, (3082 ± 56) ng/mg, (3226 ± 68) ng/mg cell protein. And they were significantly higher than those of the control group (28.9 ± 1.2) ng/mg, (2791 ± 54) ng/mg respectively (all P < 0.05). However, after preincubation of GW9662, the uptake of ox-LDL were decreased to (30.6 ± 1.3) ng/mg, (31.1 ± 1.7) ng/mg, (32.1 ± 1.8) ng/mg cell protein whereas the degradation of ox-LDL decreased to (2788 ± 53) ng/mg, (2824 ± 70) ng/mg, (2874 ± 70) ng/mg cell protein. And the difference was statistically significant when it was compared with the corresponding tAUCB-treated group. With the rising concentration of tAUCB, tAUCB could dose-dependently increase the mRNA and protein expression of CD36 and PPARγ. tAUCB could dose-dependently decrease the levels of TNF-α and increase the levels of ADP in adipocytes. GW9662 could significantly inhibit those effects of tAUCB and reduce the uptake and degradation of ox-LDL and the expression of PPARγ and CD36 in adipocytes. CONCLUSION: tAUCB can up-regulate the PPARγ expression in adipocytes and promote the uptake and degradation of ox-LDL in adipocytes via PPARγ-CD36 pathway. Meanwhile, the levels of ADP and TNF-α may be mediated through the activation of PPARγ.

Diabetic rats show reduced cardiac-somatic reflex evoked by intrapericardial capsaicin.

Painless myocardial infarction is a serious complication of diabetes. The present study examined whether cardiac nociception was altered in the streptozotocin-induced diabetic rat model by assessing intrapericardial capsaicin-evoked electromyography (EMG) responses in the spinotrapezius muscle. Somatic sensitivities to mechanical and thermal stimulation of the skin were also determined. Intrapericardial administration of capsaicin evoked a concentration-dependent EMG response, which was reproducible with repeated administration. However, the capsaicin-induced EMG responses were different in streptozotocin-induced diabetic rats and controls. Intrapericardial capsaicin produced fewer EMG responses, which were delayed and reduced in streptozotocin-treated rats compared to controls. Pretreatment with capsazepine, a TRPV1 antagonist, significantly decreased capsaicin-evoked EMG activity in both streptozotocin-treated and control rats. In addition, streptozotocin-treated rats showed a decreased paw withdrawal threshold in response to mechanical stimulation but no change in response to radiant heat stimulation. These results suggest that streptozotocin-induced diabetic rats develop somatic mechanical hypersensitivity (allodynia), but reduced cardiac nociception. Decreased TRPV1 function may contribute to the reduction of cardiac nociception in the diabetic rat.

Bradykinin is involved in the mediation of cardiac nociception during ischemia through upper thoracic spinal neurons.

Bradykinin is one of metabolites produced during myocardial ischemia and infarction that can activate cardiac spinal (sympathetic) sensory neurons to cause chest pain. The aim of this study was 1) to characterize the responses of thoracic superficial and deeper spinal neurons in rats to intrapericardial administration of bradykinin as a noxious cardiac stimulus; 2) to compare neuronal responses to bradykinin alone and a mixture of algogenic chemicals (serotonin, prostaglandin E(2), histamine, adenosine and bradykinin) used in a previous study. Extracellular potentials of single neurons in the T(3) spinal cord were recorded in pentobarbital anesthetized, paralyzed, and ventilated male rats. A catheter was placed in the pericardial sac to administer 0.2 ml solution of bradykinin (10(-5) M, 1 min). The results showed that 10/33 (30%) superficial and 80/165 (48%) deeper spinal neurons responded to intrapericardial bradykinin. All 10 superficial responsive neurons and 72/80 (90%) deeper neurons were excited; 7 (9%) neurons were inhibited; one neuron showed excitation-inhibition response pattern. Of 72 neurons excited by bradykinin, 35 and 47 neurons exhibited short- and long-lasting responses patterns, respectively. The proportions of response patterns and maximal excitatory responses to bradykinin were similar to effects obtained with a mixture of algogenic chemicals. However, the time to peak (28.3+/-3.1 s) and recovery time of long-lasting excitatory responses to bradykinin alone (125.2+/-8.9 s, n=47) were significantly shorter than the responses of neurons to the algogenic mixture (38.6+/-3.8 s and 187.5+/-18.5 s, n=49, P<0.05). In conclusion, bradykinin might play a key role in spinal processing for cardiac nociception, although other components released during ischemia might affect time characteristics of a subtype of thoracic spinal neurons receiving noxious cardiac input.

D2-like but not D1-like dopamine receptors are involved in the ventrolateral orbital cortex-induced antinociception: a GABAergic modulation mechanism.

The ventrolateral orbital cortex (VLO) is part of an endogenous analgesic system consisting of an ascending pathway from the spinal cord to VLO via the thalamic nucleus submedius (Sm) and a descending pathway to the spinal cord relaying in the periaqueductal gray (PAG). This study examines whether activation of D(1)-like and D(2)-like dopamine receptors in VLO produces antinociception and whether GABAergic modulation is involved in the VLO, D(2)-like dopamine receptor activation-evoked antinociception. The radiant heat-evoked tail flick (TF) reflex was used as an index of nociceptive response in lightly anesthetized rats. Microinjection of the D(2)-like (D(2)/D(3)) dopamine receptor agonist quinpirole (0.1-2.0 microg), but not D(1)-like (D(1)/D(5)) receptor agonist SKF-38393 (1.0, 5.0 microg), into VLO produced dose-dependent antinociception which was antagonized by the D(2)-like (D(2)/D(3)) receptor antagonist raclopride (1.5 microg). We also found that VLO application of the GABA(A) receptor antagonist bicuculline or picrotoxin (100 ng) enhanced the quinpirole-induced inhibition of the TF reflex, whereas the GABA(A) receptor agonist muscimol (250 ng) or THIP (1.0 microg) significantly attenuated the quinpirole-induced inhibition. These results suggest that D(2)-like, but not D(1)-like, dopamine receptors are involved in VLO-induced antinociception and that GABAergic disinhibitory mechanisms participate in the D(2)-like receptor mediated effect. These findings provide support for the hypothesis that D(2)-like receptor activation may inhibit the inhibitory action of the GABAergic interneurons on the output neurons projecting to PAG leading to activation of the brainstem descending inhibitory system and depression of nociceptive inputs at the spinal dorsal horn.

Effect of angiotensin II type 1 receptor on delayed rectifier potassium current in catecholaminergic CATH.a cells.

AIM: To study the modulatory effects of angiotensin II (Ang II) on the delayed rectifier potassium (Kv) current (IKv) and its underlying intracellular mechanism in the catecholaminergic system of rats. METHODS: AT1 and AT2 receptors of the differentiated and undifferentiated CATH.a cells were determined by radioligands binding assay. The IKv was recorded with the whole cell patch-clamp configuration in voltage clamp mode on CATH.a cells. RESULTS: The Ang II receptor proteins including AT1 and AT2 receptors were expressed in CATH.a cells, and the number of the former was significantly more than the latter (P<0.01). The IKv of CATH.a cells was reduced by superfusion with the Ang II (100 nmol/L) (P<0.05) in the presence of the AT2 receptor antagonist PD123319, but was not affected by only superfusion with PD123319. The effect of Ang II on IKv in CATH.a cells was completely inhibited by addition of AT1 receptor antagonist losartan. Superfusion with Ang II (100 nmol/L) plus U73122, an inhibitor of phospholipase C (PLC) in the presence of PD123319 had no effect on the IKv [(20.2+/-2.8) pA/pF]. Ang II-induced reduction of IKv was attenuated (P<0.05) but not abolished by PKC inhibitor calphostin C (Cal) and selective CaMK II inhibitor KN-93 (10 micromol/L) respectively. However, IKv reduction was completely abolished by superfusion with both Cal and KN-93. CONCLUSION: The inhibition of Kv currents in CATH.a cells by Ang II is mediated by AT1 receptor, and the PLC, PKC and CaMK II may be involved in signal transduction of AT1 receptor. The differentiated CATH.a cell is a useful cell model to study Ang II receptor-mediated functional modulation of catecholaminergic system.