Expert consensus on the diagnosis and treatment of myofascial pain syndrome.

Myofascial pain syndrome (MPS) is characterized by myofascial trigger points and fascial constrictions. At present, domestic and foreign scholars have not reached a consensus on the etiology and pathogenesis of MPS. Due to the lack of specific laboratory indicators and imaging evidence, there is no unified diagnostic criteria for MPS, making it easy to confuse with other diseases. The Chinese Association for the Study of Pain organized domestic experts to formulate this Chinese Pain Specialist Consensus on the diagnosis and treatment of MPS. This article reviews relevant domestic and foreign literature on the definition, epidemiology, pathogenesis, clinical manifestation, diagnostic criteria and treatments of MPS. The consensus is intended to normalize the diagnosis and treatment of MPS and be used by first-line doctors, including pain physicians to manage patients with MPS.

Expert consensus of the Chinese Association for the Study of Pain on pain treatment with the transdermal patch.

Chronic pain lasting more than 3 mo, or even several years can lead to disability. Treating chronic pain safely and effectively is a critical challenge faced by clinicians. Because administration of analgesics through oral, intravenous or intramuscular routes is not satisfactory, research toward percutaneous delivery has gained interest. The transdermal patch is one such percutaneous delivery system that can deliver drugs through the skin and capillaries at a certain rate to achieve a systemic or local therapeutic effect in the affected area. It has many advantages including ease of administration and hepatic first pass metabolism avoidance as well as controlling drug delivery, which reduces the dose frequency and side effects. If not required, then the patch can be removed from the skin immediately. The scopolamine patch was the first transdermal patch to be approved for the treatment of motion sickness by the Food and Drug Administration in 1979. From then on, the transdermal patch has been widely used to treat many diseases. To date, no guidelines or consensus are available on the use of analgesic drugs through transdermal delivery. The pain branch of the Chinese Medical Association, after meeting and discussing with experts and based on clinical evidence, developed a consensus for promoting and regulating standard use of transdermal patches containing analgesic drugs.

[Akt involved in diazoxide preconditioning against rat hippocampal neuronal apoptosis induced by anoxia-reoxygenation injury].

OBJECTIVE: Investigate whether preconditioning with diazoxide (DZ), a mitochondrial ATP-sensitive potassium channel opener, could enhance Akt protein to up-regulate Bcl-2/Bax protein ratio against apoptosis. METHODS: Cultured for 9 - 10 d in vitro, the hippocampal neurons of Sprague-Dawley rats were assigned to the following 5 groups randomly: Control (Group A), Anoxia (Group B), Anoxia + DZ100 micromol/L (Group C), Anoxia + DZ100 micromol/L + 5-hydroxydecanoate (Group D), Anoxia + DZ100 micromol/L + LY294002 50 micromol/L (Group E). Prior to oxygen deprivation, the hippocampal neurons were treated with DZ for 1 h per day and this treatment was persisted for 3 d. Each experiment was repeated for three times and each group contained 16 wells or 2 dishes of neurons for each time. Thereafter, neurons were derived of oxygen for 4 h. At 48 h of reoxygenation the neuronal optical density (A) were measured by MTT method, while the apoptotic rates were assayed by annexin V-FITC staining. The expressions of Akt, Bcl-2 and Bax proteins were detected and evaluated by Western blot. RESULTS: Compared with other pretreatment, DZ 100 micromol/L led to the elevation of A, whereas promoted the decrease of apoptotic rate (P < 0.05). Compared with those in other anoxic groups, the expressions of Akt protein and Bcl-2 protein in Group C were increased significantly (P < 0.05), whereas the Bax density were reduced significantly (P < 0.05). Preceding administration of 100 micromol/L DZ took protective effects on the neurons induced by anoxia-reoxygenation. CONCLUSIONS: DZ 100 micromol/L increased Akt protein to up-regulate Bcl-2/Bax protein ratio against apoptosis induced by anoxia-reoxygenation.

Diazoxide preconditioning alleviates apoptosis of hippocampal neurons induced by anoxia-reoxygenation in vitro through up-regulation of Bcl-2/Bax protein ratio.

Activating mitochondrial ATP-sensitive potassium (mitoK(ATP)) channels is a critical event of pharmacological preconditioning, which can enhance neuronal ability against various insults. mitoK(ATP) channels are abundant in neurons and can be selectively opened by diazoxide (DZ). The aim of this study was to determine whether DZ could restrain neuronal apoptosis induced by anoxia-reoxygenation and to reveal the effect of DZ preconditioning on the expressions of Bcl-2 and Bax proteins in cultured hippocampal neurons. Cultured for 9~10 d in vitro, the hippocampal neurons of Sprague-Dawley rats were assigned to the following 5 groups randomly: Control, DZ 0 mumol/L, DZ 30 mumol/L, DZ 100 mumol/L, DZ 100 mumol/L+5-hydroxydecanoate (5-HD, a selective mitoK(ATP) channel blocker) 100 mumol/L. Prior to oxygen deprivation, the hippocampal neurons except those in the control group were treated with DZ or DZ+5-HD for 1 h per day and this treatment persisted for 3 d. Thereafter, neurons were subjected to anoxia for 4 h and followed by reoxygenation. At 24 h of reoxygenation the neuronal survival rates were measured by MTT method, while the apoptotic rates were assayed by annexin V-FITC staining. The expressions of Bcl-2 and Bax proteins were detected with immunocytochemistry and evaluated by Western blot. Anoxia-reoxygenation injury reduced the survival rates and increased apoptotic rates significantly. In comparison with those in other groups, the survival rate in DZ 100 mumol/L group was increased by about 15%, whereas the apoptotic rate was decreased by almost 12% simultaneously. 5-HD could abolish the neuroprotection afforded by 100 mumol/L DZ. Bcl-2 and Bax proteins in the control normoxic neurons were both expressed slightly, while anoxia-reoxygenation led to high expression of Bax protein. The administration of 100 mumol/L DZ enhanced the expression of Bcl-2 protein by nearly 60%, whereas Bax protein was reduced by approximately 30%. Lower concentrations of DZ had no detectable effects on the expressions of Bcl-2 and Bax proteins. However, beneficial effects of DZ on the expressions of Bcl-2 and Bax proteins were reversed after the co-treatment with 5-HD. In conclusion, 100 mumol/L DZ prevented cultured hippocampal neurons from apoptosis induced by anoxia-reoxygenation possibly through up-regulating the expression of Bcl-2 protein and down-regulating the expression of Bax protein.

Diazoxide preconditioning plus subsequent hypothermia increased resistance of rat cultured hippocampal neurons against hypoxia-reoxygenation injury.

BACKGROUND: Cerebral ischemia-reperfusion/hypoxia-reoxygenation insult triggers lots of pathophysiological and biochemical events that separately affect the evolution of cerebral damage. Accordingly, all known effective neuroprotective measures should be taken to get the optimal efficacy of therapy. This study was undertaken to investigate whether diazoxide (DZ) preconditioning combined with the following hypothermia could contribute to synergistic neuroprotection compared with either hypothermia or DZ preconditioning alone. METHODS: Cultured for 9-10 days in vitro, the hippocampal neurons of SD rats were preconditioned with DZ 0 micromol/L or DZ 250 micromol/L for 1 hour per day and this treatment lasted for 3 days. Subsequently, neurons were subjected to deprivation of oxygen for 4 hours at 37 degrees C, 34 degrees C, 30 degrees C and 22 degrees C, respectively. This experiment consisted of 8 groups (4 temperature groups and 4 combination groups) and each group contained 12-well or 2-dish cells. Survival rate, expression of Bcl-2, fluorescence magnitude of intracellular calcium, and concentration of malondialdehyde (MDA) were determined at 24 hours after reoxygenation. RESULTS: The survival rate and expression of Bcl-2 were both increased in individually hypothermic conditions compared with those at 37 degrees C (P < 0.05), whereas intracellular calcium and MDA did the opposite exhibition simultaneously (P < 0.05). 22 degrees C contributed to a higher survival rate and greater expression of Bcl-2 in comparison with other hypothermia (P < 0.05). Preceding administration of 250 micromol/L DZ took the similar effects on the neurons like hypothermia. Moreover, compared with individual hypothermia or DZ preconditioning, the neuronal survival rate and expression of Bcl-2 in the combination group were increased significantly (P < 0.05), whereas the calcium fluorescence density and concentration of MDA were reduced further (P < 0.05). 250 micromol/L DZ preconditioning combined with 22 degrees C provided a maximal neuroprotection. CONCLUSIONS: Compared with either individual hypothermia or DZ preconditioning, the combination of both treatments conferred synergistic protection for cultured hippocampal neurons in vitro against hypoxia-reoxygenation insult.

[Diazoxide preconditioning combined with subsequent hypothermia alleviates anoxia-re-oxygenation injury: experiment with rat hippocampal neurons].

OBJECTIVE: To observe the alleviative effects of preconditioning with diazoxide (DZ), a mitochondrial ATP-sensitive potassium channel opener, combined with subsequent hypothermia on anoxia-re-oxygenation injury. METHODS: Hippocampal neurons of new-born SD rat were cultured. DZ of the concentration of 250 micromol/L was added into the culture fluid. The group of preconditioned cultured neurons were re-divided into 4 subgroups to be treated by hypothermia of different levels: 37 degrees C, 34 degrees C, 30 degrees C, and 22 degrees C, and then were derived of oxygen for 4 hours. The group of neurons without addition of DZ was re-divided into 4 subgroup too to be exposed to different temperatures and then underwent anoxia-re-oxygenation as described above. Thus the experiment was performed on 8 subgroups in total. Twenty-four hours after re-oxygenation the neurons were stained with dimethyl sulfoxide and their levels of absorptivity were measured so as to calculate the survival rate. Modified thiobarbital method was used to detect the concentration of malondialdehyde (MDA) in the culture fluid. Fluorescence probe Fluo-3-AM was added to detect the Ca(2+) concentration in the neurons. RESULTS: The survival rates of the DZ-preconditioned neurons of the 22 degrees C, 30 degrees C, and 34 degrees C subgroups were (94 +/- 8)%, (73 +/- 9)%, (67 +/- 8)% respectively, all significantly higher than that of the 37 degrees C subgroup (57 +/- 6%, all P < 0.01), with significant differences between the 22 degrees C subgroup and the 30 degrees C and 34 degrees C subgroups (both P < 0.01). The survival rates of the non-DZ-preconditioned neurons of the 22 degrees C, 30 degrees C, and 34 degrees C subgroups were 66 +/- 10%, 52 +/- 910%, 48 +/- 9% respectively, all significantly higher than that of the 37 degrees C subgroup (41% +/- 7%, all P < 0.01), with significant differences between the 22 degrees C subgroup and the 30 degrees C and 34 degrees C subgroups (both P < 0.01). The survival rates at different temperatures in the DZ-preconditioned group were all significantly higher than those in the corresponding non-preconditioned subgroups (all P < 0.01). The MDA concentration in the culture fluid of the 22 degrees C subgroup was significantly lower than those of the 30 degrees C, 34 degrees C, and 37 degrees C subgroups in both the DZ-preconditioned and non-preconditioned groups (all P < 0.01). The MDA concentrations of the preconditioned subgroups at different temperatures were all significantly lower than those of the corresponding non-preconditioned subgroups (all P < 0.01). The fluorescent value of the intracellular Ca(2+) of the 22 degrees C subgroup was significantly lower than those of the 30 degrees C, 34 degrees C, and 37 degrees C subgroups in both the DZ-preconditioned and non-preconditioned groups (all P < 0.01). The fluorescent value of the intracellular Ca(2+) of the preconditioned subgroups at different temperatures were all significantly lower than those of the corresponding non-preconditioned subgroups (all P < 0.01). CONCLUSION: Hypothermia alleviates the anoxia-re-oxygenation injury: DZ preconditioning enhances the neuroprotection by hypothermia.