Pathological role of PKC/TRPV1 pathway in trigeminal neuralgia in rats / 安徽医科大学学报

Objective @#To investigate the pathological role of detect protein kinase C(PKC)/ transient receptor potential vanilloid subtype 1 ( TRPV1) pathway in trigeminal neuralgia ( TN) in rats.@*Methods @#The infraorbital nerve⁃chronic constriction injury (ION⁃CCI) was used to establish a rat model of TN. The rats were randomly divided into Sham group , CCI group , CCI + DMSO group and CCI + GF109203X ( a PKC inhibitor) group. The mechanical pain threshold of the rats was measured using a Von Frey brush. qRT⁃PCR and Western blot were used to detect PKC and TRPV1 in the trigeminal ganglion (TG) . HE staining was used to observe the pathological changes of TG.@*Results @#The mechanical pain threshold significantly decreased (P < 0. 05) , and the expression of phosphorylated PKC(p⁃PKC) and TRPV1 in TG significantly increased in the CCI group (P < 0. 05) . Histopathological results showed that compared with the Sham group , the CCI group observed significant changes in TG such as increased inflammatory cell infiltration and nerve cell swelling. Injection of GF109203X effectively reduced the phosphorylation of PKC and the expression of TRPV1 in the TG of rats , and the mechanical pain threshold of the rats increased (P < 0. 05) . Under the light microscope , cell swelling and inflammatory cells in the TG were reduced.@*Conclusion @#PKC/TRPV1 pathway may be involved in trigeminal neuralgia in rats.

Analgesic mechanism of cinobufagin in rats with bone cancer pain / 中草药

Objective: To investigate the analgesic mechanism of cinobufagin in rats with bone cancer pain. Methods: Female SD rats meeting the conditions of pain threshold were selected to construct cancer-induced bone pain (CIBP) model. On the 7th day after modeling, the sham group and the model group were administrated by saline, while the treatment groups were administrated with the low, medium and high concentrations of cinobufagin for consecutive 7 d. The pain behavior (mechanical withdrawal threshold and thermal pain threshold) was tested before modeling and after modeling, and single injection of cinobufagin after 0.5, 1, 2, 4, 6, 8 and 24 h at the first day. The expression of MAPKs protein was detected by Western Blotting, and the content of spinal cytokines (IL-1β, TNF-α, MCP-1) was detected by ELISA. Results: The mechanical pain threshold and thermal pain threshold were significantly decreased in the model group, compared with the sham group (P 0.05). Protein levels of MAPKs were increased in the model group, while the levels of JNK and p38 were decreased in the cinobufagin group (P 0.05). ELISA results showed that cinobufagin significantly decreased the content of cytokines in the spinal cord, when compared with the model group (P < 0.05). Conclusion: Cinobufagin can inhibit the expression of MAPKs proteins in the spinal cord of the rat model with bone cancer pain, ultimately decrease the content of IL-1β, TNF-α, and MCP-1 to alleviate the pain during the process of cancer pain.

Effects of fatigue-predominant subhealth on mechanical and thermal pain sensitivity in mice / 中国药理学通报

Aim: To study the effects of the fatigue-predominant subhealth on mechanical and thermal pain sensitivity in mice. Methods: Kunming mice were randomly divided into two groups (n = 10); normal control group (control), fatigue-predominant subhealth model group (fatigue). The physiological behavior, rota-rod test and blood routine indexes were examined. The paw withdrawal mechanical threshold (PWMT) and the paw withdrawal thermal latency (PWTL) were measured in order to reflect the change of the mechanical and thermal pain sensitivity. Results: Compared to control group, the fur of model group was markedly pale, the time of rota-rod test was significantly lower (P < 0. 01), the data of blood cells was nearly the same, the outcome of PWMT was increased (P < 0. 01), and PWTL was decreased (P < 0. 01). Conclusions The fatigue-predominant subhealth reduces the mechanical pain sensitivity and increases the thermal pain sensitivity in mice.

Analysis on the distribution of pressure- and heat-sensitive acupoints in patients with allergic rhinitis / 针刺研究

OBJECTIVE: To explore the distribution of pressure- and heat-sensitive acupoints of the Large Intestine of Hand-Yangming, Stomach Meridian of Foot-Yangming and the Lung Meridian of Hand-Taiyin below the elbow and knee joints in patients with allergic rhinitis, so as to explore the positive reaction points at the body surface of allergic rhinitis. METHODS: Thirty variant rhinitis volunteer subjects and 30 healthy subjects were recruited in the present study. The subcutaneous induration, reaction points of emptiness-like feeling or pressing pain below the elbow- and knee-joints along the Large Intestine Meridian, Stomach Meridian and the Lung Meridian were inspected first, then re-examined by using heat-sensitized moxibustion method and a hand-held pain threshold tester (mechanical pressure), respectively. The frequency and coincidence rate of pressing-pain sensitive and heat-sensitive points were analyzed. RESULTS: In the 30 patients with allergic rhinitis, 10 positive reaction points as Kongzui (LU6), Chize (LU5), Hegu (LI4), Quchi (LI11), Shousanli(LI10), Zusanli (ST36), Shangjuxu (ST37), Fenglong (ST40), Xiajuxu (ST39), and non-acupoint of the Lung Meridian were found. Among them, the duration of heat-sensitive reaction in the LU6, LI10, ST37, ST40, and ST39 regions was obviously shorter in patients than in healthy subjects (P0.05). CONCLUSION: There is a high overlap in the distribution of pressure- and heat-sensitive acupoints of the Lung, Large Intestine and Stomach meridians below the elbow and knee joints in patients with allergic rhinitis, and there is an imbalance between the left and right limbs in the mechanical pain threshold of the pressure- and heat-sensitive acupoints, but needing being further confirmed.

Correlation Between Referred Pain Region and Sensitized Acupoints in Patients with Stable Angina Pectoris and Distribution of Sensitized Spots in Rats with Myocardial Ischemia / 针刺研究

OBJECTIVE: To observe the correlation between the referred pain regions of stable angina pectoris (SAP) and the acupoints in coronary heart disease (CHD) patients and to investigate the rule of regional sensitized point distribution in rats. METHODS: A total of 1 046 CHD patients with SAP from 8 hospitals in China were recruited in the present study. The tenderness was palpated along the left and right chest, back, shoulder, upper limb, etc. by a specially-assigned researcher in each hospital. Among them, 77 patients accepted pain threshold (PT) measurement by using a hand-held esthesiometer. In animal experiments, 14 SD rats were subjected to occlusion of the left anterior descending branch of the left coronary artery for 4 h for establishing myocardial ischemia (MI) model, and other 4 normal rats were used as the sham-operation control group. Four hours after MI, all the rats accepted tail venous injection of 5% Evans blue (50 mg/kg) for examining the distribution of the blue dye exudation spots at the body surface where the mechanical PT was also detected by a von Frey. RESULTS: In 1 046 CHD patients, 987 (94.36%) were found to have at least one tenderness spot. The tenderness spots were found at the left chest (87.47%), right chest (13.67%), left arm (ulnar side, 41.30%), right upper limb (4.68%), left shoulder back (30.21%), right shoulder back (7.07%), etc., accompanied with rash or pigmentation, subcutaneous induration, cord-like tissue contracture, skin sag, etc. The mechanical PT level was significantly lower at the tenderness spots of the left upper limb than at non-tender points of the right upper limb in CHD patients (P<0.001). Tenderness and cutaneous abnormal changes in angor pectoris patients distributed mostly on the left chest, back, shoulder and upper limb, and some also on the right. Tender points scattered on, near or outside acupoints. A similar distribution of the blue exudation spots and lower mechanical PT spots were found in MI rats, but not in sham-MI rats. CONCLUSION: In the case of MI, a regular "referred sensitization" response frequently occurs in the dermatomere area innervated by the corresponding segments (T 1－T 5) in both CHD patients and MI rats, which may be closely associated with the formation of acupoints in ancient China.

Correlative exploration in changes of mechanical pain thresholds and autophagy levels with chronic pelvic pain syndrome mice model / 中国实验动物学报

Objective To observe the changes of mechanical pain thresholds and autophagy related proteins microtubule-associated protein 1 light chain 3 (LC3) and sequestosome 1 (SQSTM1 also known as p62) expression levels in the C57BL/6 mouse models of chronic prostatitis/ chronic pelvic pain syndrome (CP/CPPS),and provide animal experimental evidence for CP/CPPS pain and autophagy study.Methods 36 male C57BL/6 mice were randomly divided into three groups: the model group,control group and na(i)ve group.The CP/CPPS model was established by subcutaneous injection in the lower abdomen region with suspension liquid,containing protein extract of male SD rat prostate gland and complete Freund adjuvant.At 1month and 6 months after modeling,the mice were sacrificed and prostate tissues were harvested for histological examination using HE staining.Mechanical tactile hyperalgesia was measured with von Frey filaments.The autophagy-related proteins LC3 and p62 expression levels were detected by immunohistochemistry,respectively.The average IOD was measured by Image Pro Plus 6.0,and the statistical analysis was performed with GraphPad Prism 5 software.Results The histopathology showed the appearance of chronic prostatitis in the model group,representing hyperplasia and lymphocytic infiltration to a different degree and lasted for 6 months after modeling.Moreover,prostate intraepithelial neoplasia (PIN) appeared in the model group at 6 months after modeling,characterized by the disappearence of basement membrane and obvious nuclear abnormality,while the control and na(i)ve groups showed normal histology during the 1-6 months.Compared with the control and na(i)ve groups,the mechanical pain threshold in the model group was significantly decreased along with the time from (0.353±0.154) g at 0 week to (0.008±0.00) g at 22 weeks (P<0.05).The average IOD of LC3 and p62 expression in the model group was significantly increased with timing from [(2.767±0.464)%,(2.872±1.642)%] at 1month to [(13.501±1.900)%,(9.07±0.49)%] at 6 month,P<0.05.Conclusions A CP/CPPS model is successfully established in C57BL/6 mice.For the model group,the mechanical pain threshold is decreased and autophagy levels are increased gradually with time.These phenomena show that chronic inflammation microenvironment may promote pain and autophagy activity in the prostate,which is closely related with the occurrence and development of prostatic intraepithelial neoplasia.

Effects of different frequencies of transcutaneous electrical nerve stimulation on venous vascular reactivity

Transcutaneous electrical nerve stimulation (TENS) is a type of therapy used primarily for analgesia, but also presents changes in the cardiovascular system responses; its effects are dependent upon application parameters. Alterations to the cardiovascular system suggest that TENS may modify venous vascular response. The objective of this study was to evaluate the effects of TENS at different frequencies (10 and 100 Hz) on venous vascular reactivity in healthy subjects. Twenty-nine healthy male volunteers were randomized into three groups: placebo (n=10), low-frequency TENS (10 Hz, n=9) and high-frequency TENS (100 Hz, n=10). TENS was applied for 30 min in the nervous plexus trajectory from the superior member (from cervical to dorsal region of the fist) at low (10 Hz/200 μs) and high frequency (100 Hz/200 μs) with its intensity adjusted below the motor threshold and intensified every 5 min, intending to avoid accommodation. Venous vascular reactivity in response to phenylephrine, acetylcholine (endothelium-dependent) and sodium nitroprusside (endothelium-independent) was assessed by the dorsal hand vein technique. The phenylephrine effective dose to achieve 70% vasoconstriction was reduced 53% (P<0.01) using low-frequency TENS (10 Hz), while in high-frequency stimulation (100 Hz), a 47% increased dose was needed (P<0.01). The endothelium-dependent (acetylcholine) and independent (sodium nitroprusside) responses were not modified by TENS, which modifies venous responsiveness, and increases the low-frequency sensitivity of α1-adrenergic receptors and shows high-frequency opposite effects. These changes represent an important vascular effect caused by TENS with implications for hemodynamics, inflammation and analgesia.

The activation of astrocytes in post herpetic neuralgia in mouce / 实用医学杂志

Objective To investigate the role of astrocytes activation in post herpetic neuralgia (PHN). Methods The kunming mice (20-25 g) were used in this study. Resiniferatoxin was injected into the peritoneal cavity.Immunofuorescence was used to detect the activation of astrocytes , mechanical paw withdrawal threshold (MWT)and thermal withdrawal latency (TWL) were used to assay the mechanical allodynia and thermal hyperalgesia, respectively. Fluorocitrate, an inhibitor of astrocytes was intrathecally (i.t.) or intraperitonealy (i. p.) injected into the mice. Results Compared with the vehicle group, MWT was decreased, and TWL was increased significantly in the RTX group. Pre-treatments of fluorocitrate (Fc, i.t.,or i.p.) inhibited the decrease of MWT. Conclusion The activation of astrocytes mediates the post herpetic neuralgia.

Modulatory effect of progesterone on peripheral pain / 第二军医大学学报

Objective: To investigate the modulatory effect oí progesterone on peripheral pain. Methods: Female SD rats were divided into four groups, namely, a vehicle group, a progesterone (500 μg) group, an RU38486 (20 μg) group and a progesterone (500 μg) plus RU38486 (20 μg) group. Von-Frey hair test was adopted to determine the peripheral mechanical pain thresholds at the following 3 ime points: preinjection, 30 min and 60 min after subcutaneous injection at the neck. Local effect of progesteronewas also tested in SD rats by Von-Frey hair test 15 min after plantar injection of progesterone (25 μg) and normal saline (control). Results: The peripheral mechanical pain threshold was significantly increased 30 min after subcutaneous injection of progesterone at the neck compared with the vehicle group, but the threshold was not significantly different 60 min after injection. RU38486 injection at the neck significantly decreased the pain threshold of plantar at 30 min and 60 min after injection, and the peripheral mechanical pain threshold was not significantly altered at 30 min and 60 min after coinjection of progesterone and RU38486. RU38486 could block the pain inhibiting effect of progesterone. The peripheral mechanical pain threshold was also increased 15 min after plantar injection of progesterone compared with the control group. Conclusion: Our findings suggest that progesterone can inhibit the peripheral mechanical pain, which might be mediated by progesterone receptor.

Association between opioid receptor gene polymorphism and postoperative pain response in Koreans

BACKGROUND: The objective of this study was to investigate the association between A118G single nucleotide polymorphism (SNP) of human micro-opioid receptor (OPRM1) gene and the postoperative pain response in Korean patients undergoing thyroidectomy. METHODS: Fifty two adult patients undergoing thyroidectomy were enrolled in this study. Their blood samples were genotyped for the A118G polymorphism. Pain intensity was assessed by a verbal numerical rating scale (VNRS) at postanesthesia care unit, postoperative 6, 24, and 48 hours. Mechanical pain threshold was assessed using electronic von Frey preoperatively and repeated at postoperative 24 and 48 hours on the forearm and periincisional regions. RESULTS: Of the 50 patients, 23 patients were A118 homozygous (AA), 19 patients were heterozygous (AG), and 8 patients were 118G homozygous (GG). The VNRS score was higher in patients with GG genotype than other genotypes at PACU (P < 0.05). Mechanical pain thresholds on the forearm and periincisional area were decreased at postoperative 24 and 48 hours from the preoperative values in all genotypes (P < 0.05). However, the changes in pain thresholds were similar among the genotypes. CONCLUSIONS: A118G SNP of OPRM1 gene is associated with inter-individual difference in immediate postoperative pain score in Korean population.

Clinical Results of Radiofrequency Dorsal Root Entry Zone Coagulation for Paraplegic Pain

OBJECTIVE: Dorsal root entry zone(DREZ) operation has been the most common surgical treatment for paraplegic pain in the past, but the results differ according to the patients. In this study, we attempt to analyze the results from the patients by the different patterns of the pain before the surgery. METHODS: A total of twelve paraplegic patients have undergone a total of thirteen radiofrequency DREZ coagulation procedures between April 1994, and March 2003. The patients were divided depending on patients' subjective description on the character, frequency, and range of pain. RESULTS: The patients were divided into the two groups, postoperatively: improvement of more than 75% of pain was defined as treatment success, and any level less than 75% of improvement was defined as treatment failure. Eight of the ten mechanical pain group cases were regarded as treatment success, and remaining two cases with thermal type of pain as treatment failure. Also, one case with combined pain failed to obtain any favorable outcome. Intermittent pain group (6 of 7 cases), continuous pain group (2 of 6 cases), and localized pain group (7 of 11 cases) showed treatment success, respectively. However, diffuse pain group (1 of 2 cases) resulted in poor outcome. CONCLUSION: Radiofrequency DREZ coagulation is more effective in managing intermittent and/or mechanical pain than continuous and/or thermal pain in the paraplegic patients following spinal cord injury.