Objective: To observe the effect of intraplantar injection of monosodium iodoacetate (MIA) on pain perception in rats and to investigate the role of transient receptor potential vanilloid type 1 (TRPV1) in the effect....Objective: To observe the effect of intraplantar injection of monosodium iodoacetate (MIA) on pain perception in rats and to investigate the role of transient receptor potential vanilloid type 1 (TRPV1) in the effect. Methods: Adult male Wistar rats were used in the experiment. 1) MIA was injected subcutaneously into the right hindpaw of rats, the low, medium, and high doses of MIA were 0.11, 0.33, and 1 mg, respectively, then the changes of paw withdrawal thermal latency, paw withdrawal mechanical threshold, and dynamic weight bearing within 4 hours after MIA injection were measured. 2) Capsazepine (TRPV1 antagonist, 30 μg) was injected subcutaneously into the right hindpaw of rats at 2 hours after intraplantar injection of MIA (1 mg), then the changes of paw withdrawal thermal latency, paw withdrawal mechanical threshold, and dynamic weight bearing within 1 hour after capsazepine injection were measured. Results: 1) The paw withdrawal thermal latency, paw withdrawal mechanical threshold, and dynamic weight bearing decreased after intraplantar injection of MIA in rats and the effect lasted for at least 4 hours. 2) The MIA-induced reduction in paw withdrawal thermal latency, paw withdrawal mechanical threshold, and dynamic weight bearing were significantly alleviated after intraplantar injection of capsazepine in rats. Conclusion: Intraplantar injection of MIA can produce thermal pain, mechanical pain, and spontaneous pain for more than 4 hours, which may be due to the TRPV1 activation caused by MIA.展开更多
In a newborn affected by a non involuting congenital hemangioma we measured allodynia through the application of a standard tactile stimulus and hyperalgesia through the regular administration of the Comfort scale whi...In a newborn affected by a non involuting congenital hemangioma we measured allodynia through the application of a standard tactile stimulus and hyperalgesia through the regular administration of the Comfort scale which rates pain intensity. The baby presented signs of these pathological events over long periods of the disease. They may be attributed to the high amount of the nociceptive ligands in the hemangioma microenviroment and to the elevated concentration of TNF-alpha and IL-6 in the blood. For a long time, the pain was relieved by a combination of opioids, adjuvants and paracetamol, but also by thalidomide and unexpectedly by interferon alpha. A mechanism-based pain treatment needs to take into account the processes underlying pain and also the ongoing pathology.展开更多
Prokineticin-1 and prokineticin receptor-1 play important roles in visceral hypersensitivity and in-flammatory pain. Visceral hypersensitivity is closely associated with irritable bowel syndrome. Mild moxibustion can ...Prokineticin-1 and prokineticin receptor-1 play important roles in visceral hypersensitivity and in-flammatory pain. Visceral hypersensitivity is closely associated with irritable bowel syndrome. Mild moxibustion can relieve chronic visceral hyperalgesia in rats with irritable bowel syndrome. We hypothesized that prokineticin-1 and prokineticin receptor-1 is the key target in the mechanism. This study established chronic visceral hyperalgesia rat models by colorectal distention. Protein and mRNA expression of prokineticin-1 and prokineticin receptor-1 were determined by immunohisto-chemical method and fluorescence quantitative-PCR, respectively, and were found to be signifi-cantly increased in visceral hyperalgesic rats. Mild moxibustion at Tianshu (ST 25) decreased prokineticin-1 and prokineticin receptor-1 expression in chronic visceral hyperalgesia rats and lessen the chronic visceral hyperalgesia in rats with irritable bowel syndrome at different levels of colorectal distention pressure.展开更多
Rats that modeled chronic visceral hyperalgesia received suspended moxibustion at bilateral Tianshu (ST25) and Shangjuxu (ST37) once daily over a period of 7 days. Results show that suspended moxibustion significa...Rats that modeled chronic visceral hyperalgesia received suspended moxibustion at bilateral Tianshu (ST25) and Shangjuxu (ST37) once daily over a period of 7 days. Results show that suspended moxibustion significantly depressed abdominal withdrawal reflex scores and increased enkephalin concentration in the spinal cord. The experimental findings suggest that spinal enkephalins contributed to the analgesic effect of suspended moxibustion in rats with chronic visceral hyperalgesia.展开更多
AIM:To evaluate the therapeutic effect of Shugan-decoction(SGD)on visceral hyperalgesia and colon gene expressions using a rat model.METHODS:Ninety-six adult male Wistar rats were randomized into six equal groups for ...AIM:To evaluate the therapeutic effect of Shugan-decoction(SGD)on visceral hyperalgesia and colon gene expressions using a rat model.METHODS:Ninety-six adult male Wistar rats were randomized into six equal groups for assessment of SGD effects on psychological stress-induced changes using the classic water avoidance stress(WAS)test.Untreated model rats were exposed to chronic(1 h/d for 10 d consecutive)WAS conditions;experimental treatment model rats were administered with intragastric SGD at1 h before WAS on consecutive days 4-10(low-dose:0.1g/mL;mid-dose:0.2 g/mL;high-dose:0.4 g/mL);control treatment model rats were similarly administered with the irritable bowel syndrome drug,dicetel(0.0042g/mL);untreated normal control rats received no drug and were not subjected to the WAS test.At the end of the 10-d WAS testing period,a semi-quantitative measurement of visceral sensitivity was made by assessing the abdominal withdrawal reflex(AWR)to colorectal balloon-induced distension(at 5 mmHg increments)to determine the pain pressure threshold(PPT,evidenced by pain behavior).Subsequently,the animals were sacrificed and colonic tissues collected for assessment of changes in expressions of proteins related to visceral hypersensitivity(transient receptor potential vanilloid 1,TRPV1)and sustained visceral hyperalgesia(substance P,SP)by immunohistochemistry and real-time polymerase chain reaction.Inter-group differences were assessed by paired t test or repeated measures analysis of variance.RESULTS:The WAS test successfully induced visceral hypersensitivity,as evidenced by a significantly reduced AWR pressure in the untreated model group as compared to the untreated normal control group(190.4±3.48 mmHg vs 224.0±4.99 mmHg,P<0.001).SGD treatments at mid-dose and high-dose and the dicetel treatment significantly increased the WAS-reduced PPT(212.5±2.54,216.5±3.50 and 217.7±2.83 mmHg respectively,all P<0.001);however,the low-dose SGD treatment produced no significant effect on the WAS-reduced PPT(198.3±1.78 mmHg,P>0.05).These trends corresponded to the differential expressions observed for both TRPV1 protein(mid-dose:1.64±0.08 and high-dose:1.69±0.12 vs untreated model:3.65±0.32,P<0.001)and mRNA(0.44±0.16 and0.15±0.03 vs 1.39±0.15,P<0.001)and SP protein(0.99±0.20 and 1.03±0.23 vs 2.03±0.12,P<0.01)and mRNA(1.64±0.19 and 1.32±0.14 vs 2.60±0.33,P<0.05).These differential expressions of TRPV1 and SP related to mid-and high-dose SGD treatments were statistically similar to the changes induced by dicetel treatment.No signs of overt damage to the rat system were observed for any of the SGD dosages.CONCLUSION:Shugan-decoction can reduce chronic stress-induced visceral hypersensitivity in rats,and the regulatory mechanism may involve mediating the expressions of TRPV1 and SP in colon tissues.展开更多
Puerarin is a major active ingredient of the traditional Chinese plant medicine,Radix Puerariae,and commonly used in the treatment of myocardial and cerebral ischemia.However,the effects of puerarin on neuropathic pai...Puerarin is a major active ingredient of the traditional Chinese plant medicine,Radix Puerariae,and commonly used in the treatment of myocardial and cerebral ischemia.However,the effects of puerarin on neuropathic pain are still unclear.In this study,a neuropathic pain animal model was created by partial sciatic nerve ligation.Puerarin(30 or 60 mg/kg) was intraperitoneally injected once a day for 7 days.Mechanical allodynia and thermal hyperalgesia were examined at 1 day after model establishment.Mechanical threshold and paw withdrawal latency markedly increased in a dose-dependent manner in puerarin-treated rats,especially at 7 days after model establishment.At 7 days after model establishment,quantitative real-time reverse transcriptase-polymerase chain reaction results showed that puerarin administration reversed m RNA expression of transient receptor potential vanilloid 1(Trpv1) and transient receptor potential ankyrin 1(Trpa1) in a dose-dependent manner in dorsal root ganglion neurons after peripheral nerve injury.These results suggest that puerarin dose-dependently ameliorates neuropathic pain by suppressing Trpv1 and Trpa1 up-regulation in dorsal root ganglion of neuropathic pain rats.展开更多
Transmembrane member 16 A(TMEM16 A) is involved in many physiological functions, such as epithelial secretion, sensory conduction, nociception, control of neuronal excitability, and regulation of smooth muscle contrac...Transmembrane member 16 A(TMEM16 A) is involved in many physiological functions, such as epithelial secretion, sensory conduction, nociception, control of neuronal excitability, and regulation of smooth muscle contraction, and may be important in peripheral pain transmission. To explore the role of TMEM16 A in the persistent hyperalgesia that results from chronic constriction injury-induced neuropathic pain, a rat model of the condition was established by ligating the left sciatic nerve. A TMEM16 A selective antagonist(10 μg T16 Ainh-A01) was intrathecally injected at L5–6. For measurement of thermal hyperalgesia, the drug was administered once at 14 days and thermal withdrawal latency was recorded with an analgesia meter. For measurement of other indexes, the drug was administered at 12 days,once every 6 hours, totally five times. The measurements were performed at 14 days. Western blot assay was conducted to analyze TMEM16 A expression in the L4–6 dorsal root ganglion. Immunofluorescence staining was used to detect the immunoreactivity of TMEM16 A in the L4–6 dorsal root ganglion on the injured side. Patch clamp was used to detect electrophysiological changes in the neurons in the L4–6 dorsal root ganglion. Our results demonstrated that thermal withdrawal latency was shortened in the model rats compared with control rats.Additionally, TMEM16 A expression and the number of TMEM16 A positive cells in the L4–6 dorsal root ganglion were higher in the model rats, which induced excitation of the neurons in the L4–6 dorsal root ganglion. These findings were inhibited by T16 Ainh-A01 and confirm that TMEM16 A plays a key role in persistent chronic constriction injury-induced hyperalgesia. Thus, inhibiting TMEM16 A might be a novel pharmacological intervention for neuropathic pain. All experimental protocols were approved by the Animal Ethics Committee at the First Affiliated Hospital of Shihezi University School of Medicine, China(approval No. A2017-170-01) on February 27, 2017.展开更多
Orthodontic tooth movement elicits alveolar bone remodeling and orofacial pain that is manifested by tooth mechanical hyperalgesia.Nerve growth factor(NGF)is upregulated in periodontium and may modulate tooth mechanic...Orthodontic tooth movement elicits alveolar bone remodeling and orofacial pain that is manifested by tooth mechanical hyperalgesia.Nerve growth factor(NGF)is upregulated in periodontium and may modulate tooth mechanical hyperalgesia.The objectives were to examine the role of NGF in tooth mechanical hyperalgesia and to elucidate the underlying mechanisms.Tooth mechanical hyperalgesia was induced by ligating closed coil springs between incisors and molars in Sprague–Dawley rats.Retrograde labeling was performed by periodontal administration of fluor-conjugated NGF and the detection of fluorescence in trigeminal ganglia(TG).Lentivirus vectors carrying NGF shRNA were employed to knockdown the expression of NGF in TG.The administration of agonists,antagonists,and virus vectors into TG and periodontium was conducted.Tooth mechanical hyperalgesia was examined through the threshold of biting withdrawal.Our results revealed that tooth movement elicited tooth mechanical hyperalgesia that could be alleviated by NGF neutralizing antibody and that NGF was upregulated in periodontium(mainly in periodontal fibroblasts)and TG.Retrograde labeling revealed that periodontal NGF was retrogradely transported to TG after day 1.Acid-sensing ion channel 3(ASIC3)and NGF were co-expressed in trigeminal neurons and the percentage of co-expression was significantly higher following tooth movement.The administration of NGF and NGF neutralizing antibody into TG could upregulate and downregulate the expression of ASIC3 in TG,respectively.NGF aggravated tooth mechanical hyperalgesia that could be alleviated by ASIC3 antagonist(APETx2).Moreover,NGF neutralizing antibody mitigated tooth mechanical hyperalgesia that could be recapitulated by ASIC3 agonist(GMQ).NGF-based gene therapy abolished tooth mechanical hyperalgesia and downregulated ASIC3 expression.Taken together,in response to force stimuli,periodontal fibroblasts upregulated the expressions of NGF that was retrogradely transported to TG,where NGF elicited tooth mechanical hyperalgesia through upregulating ASIC3.NGF-based gene therapy is a viable method in alleviating tooth-movement-induced mechanical hyperalgesia.展开更多
Opioids are drugs used to alleviate pain. However, studies have demonstrated that these drugs can cause an increase in pain sensitivity, which is called opioid-induced hyperalgesia. The objective of this study was to ...Opioids are drugs used to alleviate pain. However, studies have demonstrated that these drugs can cause an increase in pain sensitivity, which is called opioid-induced hyperalgesia. The objective of this study was to describe the effects of dexamethasone, clonidine, tramadol and nalbuphine on fentanyl-induced hyperalgesia in rats. After obtaining approval from the Committee for the Ethical Use of Animals (CEUA), 36 male Wistar rats were divided into 6 groups: Group 1 (GCSSL) wherein the rats received 1 ml 0.9% saline solution in two injections;Group 2 (GFTSL), received fentanyl at a dose of 100 ug<span style="white-space:nowrap;">·</span>kg<sup>-1</sup> followed by 1 ml 0.9% saline solution via intraperitoneal;the remaining groups (3, 4, 5, 6) received fentanyl at a dose of 100 ug<span style="white-space:nowrap;">·</span>kg<sup>-1</sup> following doses via intraperitoneal: Group 3 (GFTDX), dexamethasone at a dose of 1.0 mg<span style="white-space:nowrap;">·</span>kg<sup>-1</sup>;Group 4 (GFTCL), clonidine at a dose of 20 mg<span style="white-space:nowrap;">·</span>kg<sup>-1</sup>;Group 5 (GFTTR), tramadol at a dose of 50 mg<span style="white-space:nowrap;">·</span>kg<sup>-1</sup>, and Group 6 (GFTNB), nalbuphine at a dose of 5 mg<span style="white-space:nowrap;">·</span>kg<sup>-1</sup>. Under general anestesia using isoflurane, the animals were submitted to a surgical incision. Hyperalgesia was evaluated by applying Von Frey filaments at 2 hours after the incision and on the 1<sup>st</sup>, 3<sup>rd</sup> and 5<sup>th</sup> days afterward. At 2 hours after the surgical procedure, there was lower intensity of pain in the fentanyl group (GFTSL) compared to the other groups, and on the fifth day there were no significant differences for pain intensity between groups. The results suggest the presence of fentanyl-induced hyperalgesia and efficacy in its reduction by dexamethasone, clonidine, tramadol and nalbuphine.展开更多
Objective: To study the role of nitric oxide (NO) in the inhibition of formalin-induced hyperalgesia aller intraspinal injection of adrenocorticotropic hormone (ATCH) in rats. Methods: NADPH-d histochemistry assay of ...Objective: To study the role of nitric oxide (NO) in the inhibition of formalin-induced hyperalgesia aller intraspinal injection of adrenocorticotropic hormone (ATCH) in rats. Methods: NADPH-d histochemistry assay of the spinal cord, immuno-histochemical staining of c-fos protein (fos) and determination of the content of gama-aminobutyric acid (CABA) of ’ the spinal spinal cord tissue were performed Results: lntraspinal injection,of ACTH significantly inhibited the increase of nitrie oxide synthetase (NOS)positive . neurons, fos-positive neurons and the elevation of GABA level in the lumbar seg ment of the spinal cord which could be partially reversed with the adminnistration of 10 μmol L-arginine (Arg)Conclu- sion:The decrease of NO synthesis might play a part in the inhibition of formalin -induced hyperalgesia after intraspinal injec- tion of ACTH展开更多
Opioid-induced hyperalgesia negatively affects physiological pain management and presents a complex causal mechanism, involving, pharmacodynamic and pharmacokinetic factors of interactions with receptors, opioid-indep...Opioid-induced hyperalgesia negatively affects physiological pain management and presents a complex causal mechanism, involving, pharmacodynamic and pharmacokinetic factors of interactions with receptors, opioid-independent ascending systems and with pro-nociceptive systems. After approval by the CEUA, 42 male Wistar rats were divided into 7 groups: In group 1 (GCSSL) the animals received 1 ml of 0.9% saline solution intraperitoneally (IP);in group 2 (GFTSL), they received fentanyl at a dose of 100 ug·kg<sup>-1</sup> IP;in the remaining groups (3, 4, 5, 6 and 7) the animals received IP, fentanyl at a dose of 100 ug·kg<sup>-1</sup> followed also by IP route of: group 3 (GFTKP) ketoprofen at a dose of 5 mg·kg<sup>-1</sup>;group 4 GFTKT), ketamine up to a dose of 10.0 mg·kg<sup>-1</sup>;group 5 (GFTLI), incisional lidocaine up to a dose of 10 mg·kg<sup>-1</sup>;group 6 (GFTLP), intraperitoneal lidocaine up to a dose of 10 mg·kg<sup>-1</sup> and group 7 (GFTPP), propofol up to a dose of 60 mg·kg<sup>-1</sup>. Under general anesthesia, all animals with a plantar surgical incision. Hyperalgesia was evaluated by applying Von Frey filaments on the 2nd, 1st, 3rd and 5th days after treatment. In the 2nd hour and on the 5th day after the procedure, there was no hyperalgesia associated with the use of fentanyl, however, on the 1st and 3rd postoperative days there was hyperalgesia that was attenuated by ketoprofen, ketamine, lidocaine infiltrated in the incision and intraperitoneally, an effect not observed with the use of propofol. The results suggest fentanyl-induced hyperalgesia and the efficacy of ketoprofen, ketamine, incisional lidocaine and intraperitoneal lidocaine in reducing this effect.展开更多
Tobacco smoking is considered to be one of the main risk factors in the development of chronic pain.Long-term chronic exposure to nicotine and other forms of tobacco have been shown to be associated with an increased ...Tobacco smoking is considered to be one of the main risk factors in the development of chronic pain.Long-term chronic exposure to nicotine and other forms of tobacco have been shown to be associated with an increased incidence of pain.Studies have shown that acupuncture can help smokers to reduce their desire to smoke,reduce their withdrawal symptoms,and avoid a relapse after treatment.However,little has been reported about the effects of acupuncture on pain sensitivity caused by long-term smoking.Models of hyperalgesia were established in rats exposed to nicotine for 6 weeks.After 6 weeks of continuous nicotine exposure,electroacupuncture at bilateral acupoints Zusanli(ST36)and Taichong(LR3)was performed 20 minutes per day for 6 days at a continuous wave with a frequency of 2 Hz and a stimulus intensity of 1 m A.The results revealed that electroacupuncture treatment increased the mechanical response threshold of hind paw of nicotine-dependent rats with hyperalgesia and up-regulated the protein expression of pain-related factorsμ-opioid receptor,β-endorphin and glutamic acid decarboxylase 65 in the spinal cord and midbrain periaqueductal gray and the protein expression of glutamic acid decarboxylase 67 in the spinal cord.These findings suggest that electroacupuncture treatment has positive analgesic effects on pain sensitivity caused by long-term chronic nicotine exposure.One possible mechanism for the improved analgesia is that electroacupuncture increases the expression of painrelated factors in the spinal cord and midbrain periaqueductal gray.This study was approved by Institutional Animal Care and Use Committee(IACUC)of the University of Miami(#18-167)on December 12,2018.展开更多
Aim: Diabetic neuropathic pain is one of the pains which hardly respond to pharmaceutical treat. Today, various chemical and herbal compounds have been used to reduce pain. The aim of this study is to compare the effe...Aim: Diabetic neuropathic pain is one of the pains which hardly respond to pharmaceutical treat. Today, various chemical and herbal compounds have been used to reduce pain. The aim of this study is to compare the effect of date extract and melatonin in preventing pain in diabetic rats.Method: To study hyperalgesia response and to compare the effect of date extract and melatonin in preventing pain, hot plate and tail flick tests were used. After prescribing single dose of streptozotocin to rats and approving their diabetes, treatment rats received date extract (4ml/kg/day) or melatonin [10 mg/kg/day, intraperitoneally (i.p.)] for a period of 6 weeks. At the end of the sixth week, control and treated rats were examined by thermal pain response and explorative activity tests.Results: According to hot plate results, response time to thermal pain in treated group showed a significant decrease in comparison with the control group (P 0.01). Prescription of date extract increased response time to thermal pain in comparison with treated group (P 0.01), so that response time approximated to control group. Although melatonin approximated to the response time to control group, the significant difference was not observed among melatonin receivers and other groups. In the assessment of diabetic neuropathy on the explorative activity of rats in an open field behavioral test, total distance moved and rearing frequency were significantly decreased, while administration of date extract did also improve motor deficits induced by STZ. Conclusions:Findings of this study showed that date extract decreased thermal hyperalgesia and can prevent pain resulted from diabetic neuropathy.展开更多
Central sensitizationis critical for chronic pain sensation induced by chronic pancreatitis(CP).We hypothesized that the nucleus tractus solitarius(NTS),a primary central site that integrates pancreatic afferents apar...Central sensitizationis critical for chronic pain sensation induced by chronic pancreatitis(CP).We hypothesized that the nucleus tractus solitarius(NTS),a primary central site that integrates pancreatic afferents apart from the thoracic spinal dorsal horn,plays a key role in the pathogenesis of visceral hypersensitivity in a rat model of CP.In order to investigate the role of the NTS in the visceral hypersensitivity induced by chronic pancreatitis,CP was induced by the intraductal injection of trinitrobenzene sulfonic acid(TNBS)in rats.Pancreatic hyperalgesia was assessed by referred somatic pain via von Frey filament assay.Neural activation of the NTS was indicated by Fos-immunohistochemical staining.展开更多
OBJECTIVE: To evaluate the effect of berberine on morphine analgesia, tolerance, and hyperalgesia. METHODS: Morphine-induced acute tolerance model: mice received intraperitoneal berberine at doses of 2.5, 5.0, and 10 ...OBJECTIVE: To evaluate the effect of berberine on morphine analgesia, tolerance, and hyperalgesia. METHODS: Morphine-induced acute tolerance model: mice received intraperitoneal berberine at doses of 2.5, 5.0, and 10 mg/kg;30 min later, subcutaneous morphine 10 mg/kg was injected every hour for nine continuous h. Morphine 10 mg/kg alone was administered at 24 and 48 h. Morphine-induced chronic tolerance model: mice received intraperitoneal berberine 2.5, 5.0, and 10 mg/kg;30 min later, 10 mg/kg morphine was injected subcutaneously for eight consecutive days. On the ninth day, morphine 10 mg/kg was given alone. Morphineinduced established tolerance model: mice were injected subcutaneously with morphine 10 mg/kg once a day for eight consecutive days. Berberine 2.5 mg/kg was administered on day one, four, and seven and morphine 10 mg/kg alone on day nine. The baseline latency(T0) and post-treatment latency(T1) were determined by the hot plate test, and the maximum possible analgesic effect (MPAE) was calculated. Nitric oxide synthase(NOS) activity and nitric oxide(NO) content in the spinal cord were measured by spectrophotometer. Verification of berberine analgesic effect by blocking N-methyl-Daspartate(NMDA) receptor: HT-22 and HEK-293 cells transfected with NMDA plasmid were randomly divided into five groups: control group, NMDA group, berberine low-dose, medium-dose, and high-dose groups(5, 10, 20 μmol/L, respectively). Except for the control group, cells were treated with NMDA(HT-22 cells: 20 mmol/L;HEK-293 cells: 50 μmol/L). After 24 h, cell viability was detected by cell counting kit-8. The molecular mechanism between berberine and the NMDA receptor was studied by molecular docking. RESULTS: Berberine 2.5 and 5.0 mg/kg could prolong the analgesic time of morphine. In acute and chronic morphine tolerance models, berberine could inhibit the decrease of MPAE and baseline latency(P < 0.05). In the established tolerance model, berberine could rapidly reverse the decreased MPAE(P < 0.05). The combination of berberine and morphine on day one could effectively inhibit the morphine-induced increase of NOS activity and NO content in the spinal cord(P < 0.05). Berberine significantly increased the cell viability of NMDA-induced nerve injury in HT-22 and HEK-293 cells(P < 0.05). Molecular docking showed that berberine binds to the receptor pocket of NMDA. CONCLUSIONS: Berberine could effectively enhance and prolong the duration of morphine analgesia and inhibit the development of morphine-induced tolerance and hyperalgesia. Furthermore, berberine has a certain neuroprotective effect, which may be related to the inhibition of NMDA activity.展开更多
OBJECTIVE: To investigate the analgesic effect of Gua Sha and its underlying mechanism in rats with noncompressive lumbar disk herniation induced by autologous nucleus pulposus.METHODS: A rat model of noncompressive l...OBJECTIVE: To investigate the analgesic effect of Gua Sha and its underlying mechanism in rats with noncompressive lumbar disk herniation induced by autologous nucleus pulposus.METHODS: A rat model of noncompressive lumbar disk herniation was established and rats were randomly divided into model group, sham group, and Gua Sha group(24 in each group). Gua Sha was performed from the 5 th day after the surgery, once every other day, 3 times for a course of treatment,and totally 3 courses. The thermal withdrawal latency was evaluated using the intelligent hot plate one day before the surgery, and on days 4(the day before the treatment), 10(the end of the firstcourse), 16(the end of the second course) and 22(the end of the third course). On days 4, 10, 16 and22, six rats in each group were picked randomly and their blood samples were drawn to assess the expression of interleukin-1β(IL-1β), interleukin-6(IL-6) and tumor necrosis factor-alpha(TNF-α).RESULTS: Compared to rats in the sham group, the application of nucleus pulposus to right L5 dorsal root ganglion induced prolonged thermal hyperalgesia, and up-regulated the expression of IL-1β,IL-6 and TNF-α in serum(P < 0.01). The therapy of Gua Sha attenuated thermal hyperalgesia potently,inhibited the expression of IL-1β, IL-6 and TNF-α in a time-dependent manner(P < 0.01). There were no significant differences in the thermal withdrawal latency and the expression of inflammatory cytokines between the sham and Gua Sha groups at the end of the treatment(P > 0.01).CONCLUSION: The current study showed that Gua Sha might alleviate thermal hyperalgesia in rats with lumbar disc herniation induced by autologous nucleus pulposus via inhibiting the expression of proinflammatory cytokins.展开更多
文摘Objective: To observe the effect of intraplantar injection of monosodium iodoacetate (MIA) on pain perception in rats and to investigate the role of transient receptor potential vanilloid type 1 (TRPV1) in the effect. Methods: Adult male Wistar rats were used in the experiment. 1) MIA was injected subcutaneously into the right hindpaw of rats, the low, medium, and high doses of MIA were 0.11, 0.33, and 1 mg, respectively, then the changes of paw withdrawal thermal latency, paw withdrawal mechanical threshold, and dynamic weight bearing within 4 hours after MIA injection were measured. 2) Capsazepine (TRPV1 antagonist, 30 μg) was injected subcutaneously into the right hindpaw of rats at 2 hours after intraplantar injection of MIA (1 mg), then the changes of paw withdrawal thermal latency, paw withdrawal mechanical threshold, and dynamic weight bearing within 1 hour after capsazepine injection were measured. Results: 1) The paw withdrawal thermal latency, paw withdrawal mechanical threshold, and dynamic weight bearing decreased after intraplantar injection of MIA in rats and the effect lasted for at least 4 hours. 2) The MIA-induced reduction in paw withdrawal thermal latency, paw withdrawal mechanical threshold, and dynamic weight bearing were significantly alleviated after intraplantar injection of capsazepine in rats. Conclusion: Intraplantar injection of MIA can produce thermal pain, mechanical pain, and spontaneous pain for more than 4 hours, which may be due to the TRPV1 activation caused by MIA.
文摘In a newborn affected by a non involuting congenital hemangioma we measured allodynia through the application of a standard tactile stimulus and hyperalgesia through the regular administration of the Comfort scale which rates pain intensity. The baby presented signs of these pathological events over long periods of the disease. They may be attributed to the high amount of the nociceptive ligands in the hemangioma microenviroment and to the elevated concentration of TNF-alpha and IL-6 in the blood. For a long time, the pain was relieved by a combination of opioids, adjuvants and paracetamol, but also by thalidomide and unexpectedly by interferon alpha. A mechanism-based pain treatment needs to take into account the processes underlying pain and also the ongoing pathology.
基金the National Basic Research Program of China (973 program), No.2009CB522900Shanghai Leading Academic Discipline Project, No. S30304+1 种基金 National Natural Science Foundation of China, No.81001549 Specialized Research Fund for the Doctoral Program of Higher Education, No.200802680001
文摘Prokineticin-1 and prokineticin receptor-1 play important roles in visceral hypersensitivity and in-flammatory pain. Visceral hypersensitivity is closely associated with irritable bowel syndrome. Mild moxibustion can relieve chronic visceral hyperalgesia in rats with irritable bowel syndrome. We hypothesized that prokineticin-1 and prokineticin receptor-1 is the key target in the mechanism. This study established chronic visceral hyperalgesia rat models by colorectal distention. Protein and mRNA expression of prokineticin-1 and prokineticin receptor-1 were determined by immunohisto-chemical method and fluorescence quantitative-PCR, respectively, and were found to be signifi-cantly increased in visceral hyperalgesic rats. Mild moxibustion at Tianshu (ST 25) decreased prokineticin-1 and prokineticin receptor-1 expression in chronic visceral hyperalgesia rats and lessen the chronic visceral hyperalgesia in rats with irritable bowel syndrome at different levels of colorectal distention pressure.
基金supported by the National Basic Research Program of China (973 Program) (No. 2009CB522900)the National Natural Science Foundation of China (No. 30973783)the Shanghai Leading Academic Discipline Project (No. S30304)
文摘Rats that modeled chronic visceral hyperalgesia received suspended moxibustion at bilateral Tianshu (ST25) and Shangjuxu (ST37) once daily over a period of 7 days. Results show that suspended moxibustion significantly depressed abdominal withdrawal reflex scores and increased enkephalin concentration in the spinal cord. The experimental findings suggest that spinal enkephalins contributed to the analgesic effect of suspended moxibustion in rats with chronic visceral hyperalgesia.
基金Supported by National Natural Science Foundation of China,No.81072786the Innovation Program of the Shanghai Municipal Education Commission,No.12YZ065the Longhua Medical Project,No.D-09
文摘AIM:To evaluate the therapeutic effect of Shugan-decoction(SGD)on visceral hyperalgesia and colon gene expressions using a rat model.METHODS:Ninety-six adult male Wistar rats were randomized into six equal groups for assessment of SGD effects on psychological stress-induced changes using the classic water avoidance stress(WAS)test.Untreated model rats were exposed to chronic(1 h/d for 10 d consecutive)WAS conditions;experimental treatment model rats were administered with intragastric SGD at1 h before WAS on consecutive days 4-10(low-dose:0.1g/mL;mid-dose:0.2 g/mL;high-dose:0.4 g/mL);control treatment model rats were similarly administered with the irritable bowel syndrome drug,dicetel(0.0042g/mL);untreated normal control rats received no drug and were not subjected to the WAS test.At the end of the 10-d WAS testing period,a semi-quantitative measurement of visceral sensitivity was made by assessing the abdominal withdrawal reflex(AWR)to colorectal balloon-induced distension(at 5 mmHg increments)to determine the pain pressure threshold(PPT,evidenced by pain behavior).Subsequently,the animals were sacrificed and colonic tissues collected for assessment of changes in expressions of proteins related to visceral hypersensitivity(transient receptor potential vanilloid 1,TRPV1)and sustained visceral hyperalgesia(substance P,SP)by immunohistochemistry and real-time polymerase chain reaction.Inter-group differences were assessed by paired t test or repeated measures analysis of variance.RESULTS:The WAS test successfully induced visceral hypersensitivity,as evidenced by a significantly reduced AWR pressure in the untreated model group as compared to the untreated normal control group(190.4±3.48 mmHg vs 224.0±4.99 mmHg,P<0.001).SGD treatments at mid-dose and high-dose and the dicetel treatment significantly increased the WAS-reduced PPT(212.5±2.54,216.5±3.50 and 217.7±2.83 mmHg respectively,all P<0.001);however,the low-dose SGD treatment produced no significant effect on the WAS-reduced PPT(198.3±1.78 mmHg,P>0.05).These trends corresponded to the differential expressions observed for both TRPV1 protein(mid-dose:1.64±0.08 and high-dose:1.69±0.12 vs untreated model:3.65±0.32,P<0.001)and mRNA(0.44±0.16 and0.15±0.03 vs 1.39±0.15,P<0.001)and SP protein(0.99±0.20 and 1.03±0.23 vs 2.03±0.12,P<0.01)and mRNA(1.64±0.19 and 1.32±0.14 vs 2.60±0.33,P<0.05).These differential expressions of TRPV1 and SP related to mid-and high-dose SGD treatments were statistically similar to the changes induced by dicetel treatment.No signs of overt damage to the rat system were observed for any of the SGD dosages.CONCLUSION:Shugan-decoction can reduce chronic stress-induced visceral hypersensitivity in rats,and the regulatory mechanism may involve mediating the expressions of TRPV1 and SP in colon tissues.
基金supported by the National Natural Science Foundation of China,No.81671891
文摘Puerarin is a major active ingredient of the traditional Chinese plant medicine,Radix Puerariae,and commonly used in the treatment of myocardial and cerebral ischemia.However,the effects of puerarin on neuropathic pain are still unclear.In this study,a neuropathic pain animal model was created by partial sciatic nerve ligation.Puerarin(30 or 60 mg/kg) was intraperitoneally injected once a day for 7 days.Mechanical allodynia and thermal hyperalgesia were examined at 1 day after model establishment.Mechanical threshold and paw withdrawal latency markedly increased in a dose-dependent manner in puerarin-treated rats,especially at 7 days after model establishment.At 7 days after model establishment,quantitative real-time reverse transcriptase-polymerase chain reaction results showed that puerarin administration reversed m RNA expression of transient receptor potential vanilloid 1(Trpv1) and transient receptor potential ankyrin 1(Trpa1) in a dose-dependent manner in dorsal root ganglion neurons after peripheral nerve injury.These results suggest that puerarin dose-dependently ameliorates neuropathic pain by suppressing Trpv1 and Trpa1 up-regulation in dorsal root ganglion of neuropathic pain rats.
基金supported by the National Natural Science Foundation of China,No.30160026(to JQS)the High Level Talent Research Project of Shihezi University of China,No.RCSX201705(to YW)
文摘Transmembrane member 16 A(TMEM16 A) is involved in many physiological functions, such as epithelial secretion, sensory conduction, nociception, control of neuronal excitability, and regulation of smooth muscle contraction, and may be important in peripheral pain transmission. To explore the role of TMEM16 A in the persistent hyperalgesia that results from chronic constriction injury-induced neuropathic pain, a rat model of the condition was established by ligating the left sciatic nerve. A TMEM16 A selective antagonist(10 μg T16 Ainh-A01) was intrathecally injected at L5–6. For measurement of thermal hyperalgesia, the drug was administered once at 14 days and thermal withdrawal latency was recorded with an analgesia meter. For measurement of other indexes, the drug was administered at 12 days,once every 6 hours, totally five times. The measurements were performed at 14 days. Western blot assay was conducted to analyze TMEM16 A expression in the L4–6 dorsal root ganglion. Immunofluorescence staining was used to detect the immunoreactivity of TMEM16 A in the L4–6 dorsal root ganglion on the injured side. Patch clamp was used to detect electrophysiological changes in the neurons in the L4–6 dorsal root ganglion. Our results demonstrated that thermal withdrawal latency was shortened in the model rats compared with control rats.Additionally, TMEM16 A expression and the number of TMEM16 A positive cells in the L4–6 dorsal root ganglion were higher in the model rats, which induced excitation of the neurons in the L4–6 dorsal root ganglion. These findings were inhibited by T16 Ainh-A01 and confirm that TMEM16 A plays a key role in persistent chronic constriction injury-induced hyperalgesia. Thus, inhibiting TMEM16 A might be a novel pharmacological intervention for neuropathic pain. All experimental protocols were approved by the Animal Ethics Committee at the First Affiliated Hospital of Shihezi University School of Medicine, China(approval No. A2017-170-01) on February 27, 2017.
基金the National Natural Science Foundation of China(Nos.82071147,81571004,and 81500884)Sichuan Science and Technology Program(Nos.2018JY0558,2021YJ0428,and 2018SZ0232)+2 种基金Research Grant of Health Commission of Sichuan Province(Nos.19PJ233 and 20PJ090)CSA Clinical Research Fund(CSA-02020-02)Research and Develop Program,West China Hospital of Stomatology,Sichuan University(Nos.LCYJ2020-TD-2 and WCHS-201704).
文摘Orthodontic tooth movement elicits alveolar bone remodeling and orofacial pain that is manifested by tooth mechanical hyperalgesia.Nerve growth factor(NGF)is upregulated in periodontium and may modulate tooth mechanical hyperalgesia.The objectives were to examine the role of NGF in tooth mechanical hyperalgesia and to elucidate the underlying mechanisms.Tooth mechanical hyperalgesia was induced by ligating closed coil springs between incisors and molars in Sprague–Dawley rats.Retrograde labeling was performed by periodontal administration of fluor-conjugated NGF and the detection of fluorescence in trigeminal ganglia(TG).Lentivirus vectors carrying NGF shRNA were employed to knockdown the expression of NGF in TG.The administration of agonists,antagonists,and virus vectors into TG and periodontium was conducted.Tooth mechanical hyperalgesia was examined through the threshold of biting withdrawal.Our results revealed that tooth movement elicited tooth mechanical hyperalgesia that could be alleviated by NGF neutralizing antibody and that NGF was upregulated in periodontium(mainly in periodontal fibroblasts)and TG.Retrograde labeling revealed that periodontal NGF was retrogradely transported to TG after day 1.Acid-sensing ion channel 3(ASIC3)and NGF were co-expressed in trigeminal neurons and the percentage of co-expression was significantly higher following tooth movement.The administration of NGF and NGF neutralizing antibody into TG could upregulate and downregulate the expression of ASIC3 in TG,respectively.NGF aggravated tooth mechanical hyperalgesia that could be alleviated by ASIC3 antagonist(APETx2).Moreover,NGF neutralizing antibody mitigated tooth mechanical hyperalgesia that could be recapitulated by ASIC3 agonist(GMQ).NGF-based gene therapy abolished tooth mechanical hyperalgesia and downregulated ASIC3 expression.Taken together,in response to force stimuli,periodontal fibroblasts upregulated the expressions of NGF that was retrogradely transported to TG,where NGF elicited tooth mechanical hyperalgesia through upregulating ASIC3.NGF-based gene therapy is a viable method in alleviating tooth-movement-induced mechanical hyperalgesia.
文摘Opioids are drugs used to alleviate pain. However, studies have demonstrated that these drugs can cause an increase in pain sensitivity, which is called opioid-induced hyperalgesia. The objective of this study was to describe the effects of dexamethasone, clonidine, tramadol and nalbuphine on fentanyl-induced hyperalgesia in rats. After obtaining approval from the Committee for the Ethical Use of Animals (CEUA), 36 male Wistar rats were divided into 6 groups: Group 1 (GCSSL) wherein the rats received 1 ml 0.9% saline solution in two injections;Group 2 (GFTSL), received fentanyl at a dose of 100 ug<span style="white-space:nowrap;">·</span>kg<sup>-1</sup> followed by 1 ml 0.9% saline solution via intraperitoneal;the remaining groups (3, 4, 5, 6) received fentanyl at a dose of 100 ug<span style="white-space:nowrap;">·</span>kg<sup>-1</sup> following doses via intraperitoneal: Group 3 (GFTDX), dexamethasone at a dose of 1.0 mg<span style="white-space:nowrap;">·</span>kg<sup>-1</sup>;Group 4 (GFTCL), clonidine at a dose of 20 mg<span style="white-space:nowrap;">·</span>kg<sup>-1</sup>;Group 5 (GFTTR), tramadol at a dose of 50 mg<span style="white-space:nowrap;">·</span>kg<sup>-1</sup>, and Group 6 (GFTNB), nalbuphine at a dose of 5 mg<span style="white-space:nowrap;">·</span>kg<sup>-1</sup>. Under general anestesia using isoflurane, the animals were submitted to a surgical incision. Hyperalgesia was evaluated by applying Von Frey filaments at 2 hours after the incision and on the 1<sup>st</sup>, 3<sup>rd</sup> and 5<sup>th</sup> days afterward. At 2 hours after the surgical procedure, there was lower intensity of pain in the fentanyl group (GFTSL) compared to the other groups, and on the fifth day there were no significant differences for pain intensity between groups. The results suggest the presence of fentanyl-induced hyperalgesia and efficacy in its reduction by dexamethasone, clonidine, tramadol and nalbuphine.
文摘Objective: To study the role of nitric oxide (NO) in the inhibition of formalin-induced hyperalgesia aller intraspinal injection of adrenocorticotropic hormone (ATCH) in rats. Methods: NADPH-d histochemistry assay of the spinal cord, immuno-histochemical staining of c-fos protein (fos) and determination of the content of gama-aminobutyric acid (CABA) of ’ the spinal spinal cord tissue were performed Results: lntraspinal injection,of ACTH significantly inhibited the increase of nitrie oxide synthetase (NOS)positive . neurons, fos-positive neurons and the elevation of GABA level in the lumbar seg ment of the spinal cord which could be partially reversed with the adminnistration of 10 μmol L-arginine (Arg)Conclu- sion:The decrease of NO synthesis might play a part in the inhibition of formalin -induced hyperalgesia after intraspinal injec- tion of ACTH
文摘Opioid-induced hyperalgesia negatively affects physiological pain management and presents a complex causal mechanism, involving, pharmacodynamic and pharmacokinetic factors of interactions with receptors, opioid-independent ascending systems and with pro-nociceptive systems. After approval by the CEUA, 42 male Wistar rats were divided into 7 groups: In group 1 (GCSSL) the animals received 1 ml of 0.9% saline solution intraperitoneally (IP);in group 2 (GFTSL), they received fentanyl at a dose of 100 ug·kg<sup>-1</sup> IP;in the remaining groups (3, 4, 5, 6 and 7) the animals received IP, fentanyl at a dose of 100 ug·kg<sup>-1</sup> followed also by IP route of: group 3 (GFTKP) ketoprofen at a dose of 5 mg·kg<sup>-1</sup>;group 4 GFTKT), ketamine up to a dose of 10.0 mg·kg<sup>-1</sup>;group 5 (GFTLI), incisional lidocaine up to a dose of 10 mg·kg<sup>-1</sup>;group 6 (GFTLP), intraperitoneal lidocaine up to a dose of 10 mg·kg<sup>-1</sup> and group 7 (GFTPP), propofol up to a dose of 60 mg·kg<sup>-1</sup>. Under general anesthesia, all animals with a plantar surgical incision. Hyperalgesia was evaluated by applying Von Frey filaments on the 2nd, 1st, 3rd and 5th days after treatment. In the 2nd hour and on the 5th day after the procedure, there was no hyperalgesia associated with the use of fentanyl, however, on the 1st and 3rd postoperative days there was hyperalgesia that was attenuated by ketoprofen, ketamine, lidocaine infiltrated in the incision and intraperitoneally, an effect not observed with the use of propofol. The results suggest fentanyl-induced hyperalgesia and the efficacy of ketoprofen, ketamine, incisional lidocaine and intraperitoneal lidocaine in reducing this effect.
基金supported by a grant from Department of Anesthesiology,Perioperative Medicine and Pain Management,University of Miami Miller School of Medicine,USA。
文摘Tobacco smoking is considered to be one of the main risk factors in the development of chronic pain.Long-term chronic exposure to nicotine and other forms of tobacco have been shown to be associated with an increased incidence of pain.Studies have shown that acupuncture can help smokers to reduce their desire to smoke,reduce their withdrawal symptoms,and avoid a relapse after treatment.However,little has been reported about the effects of acupuncture on pain sensitivity caused by long-term smoking.Models of hyperalgesia were established in rats exposed to nicotine for 6 weeks.After 6 weeks of continuous nicotine exposure,electroacupuncture at bilateral acupoints Zusanli(ST36)and Taichong(LR3)was performed 20 minutes per day for 6 days at a continuous wave with a frequency of 2 Hz and a stimulus intensity of 1 m A.The results revealed that electroacupuncture treatment increased the mechanical response threshold of hind paw of nicotine-dependent rats with hyperalgesia and up-regulated the protein expression of pain-related factorsμ-opioid receptor,β-endorphin and glutamic acid decarboxylase 65 in the spinal cord and midbrain periaqueductal gray and the protein expression of glutamic acid decarboxylase 67 in the spinal cord.These findings suggest that electroacupuncture treatment has positive analgesic effects on pain sensitivity caused by long-term chronic nicotine exposure.One possible mechanism for the improved analgesia is that electroacupuncture increases the expression of painrelated factors in the spinal cord and midbrain periaqueductal gray.This study was approved by Institutional Animal Care and Use Committee(IACUC)of the University of Miami(#18-167)on December 12,2018.
文摘Aim: Diabetic neuropathic pain is one of the pains which hardly respond to pharmaceutical treat. Today, various chemical and herbal compounds have been used to reduce pain. The aim of this study is to compare the effect of date extract and melatonin in preventing pain in diabetic rats.Method: To study hyperalgesia response and to compare the effect of date extract and melatonin in preventing pain, hot plate and tail flick tests were used. After prescribing single dose of streptozotocin to rats and approving their diabetes, treatment rats received date extract (4ml/kg/day) or melatonin [10 mg/kg/day, intraperitoneally (i.p.)] for a period of 6 weeks. At the end of the sixth week, control and treated rats were examined by thermal pain response and explorative activity tests.Results: According to hot plate results, response time to thermal pain in treated group showed a significant decrease in comparison with the control group (P 0.01). Prescription of date extract increased response time to thermal pain in comparison with treated group (P 0.01), so that response time approximated to control group. Although melatonin approximated to the response time to control group, the significant difference was not observed among melatonin receivers and other groups. In the assessment of diabetic neuropathy on the explorative activity of rats in an open field behavioral test, total distance moved and rearing frequency were significantly decreased, while administration of date extract did also improve motor deficits induced by STZ. Conclusions:Findings of this study showed that date extract decreased thermal hyperalgesia and can prevent pain resulted from diabetic neuropathy.
文摘Central sensitizationis critical for chronic pain sensation induced by chronic pancreatitis(CP).We hypothesized that the nucleus tractus solitarius(NTS),a primary central site that integrates pancreatic afferents apart from the thoracic spinal dorsal horn,plays a key role in the pathogenesis of visceral hypersensitivity in a rat model of CP.In order to investigate the role of the NTS in the visceral hypersensitivity induced by chronic pancreatitis,CP was induced by the intraductal injection of trinitrobenzene sulfonic acid(TNBS)in rats.Pancreatic hyperalgesia was assessed by referred somatic pain via von Frey filament assay.Neural activation of the NTS was indicated by Fos-immunohistochemical staining.
基金Natural Science Foundation of Shandong Province:Mechanism of the Compound Huanglian Decoction Against Morphine Tolerance Based on Network Pharmacology and Microglia M1/M2 Pattern(No.ZR2023MH270)。
文摘OBJECTIVE: To evaluate the effect of berberine on morphine analgesia, tolerance, and hyperalgesia. METHODS: Morphine-induced acute tolerance model: mice received intraperitoneal berberine at doses of 2.5, 5.0, and 10 mg/kg;30 min later, subcutaneous morphine 10 mg/kg was injected every hour for nine continuous h. Morphine 10 mg/kg alone was administered at 24 and 48 h. Morphine-induced chronic tolerance model: mice received intraperitoneal berberine 2.5, 5.0, and 10 mg/kg;30 min later, 10 mg/kg morphine was injected subcutaneously for eight consecutive days. On the ninth day, morphine 10 mg/kg was given alone. Morphineinduced established tolerance model: mice were injected subcutaneously with morphine 10 mg/kg once a day for eight consecutive days. Berberine 2.5 mg/kg was administered on day one, four, and seven and morphine 10 mg/kg alone on day nine. The baseline latency(T0) and post-treatment latency(T1) were determined by the hot plate test, and the maximum possible analgesic effect (MPAE) was calculated. Nitric oxide synthase(NOS) activity and nitric oxide(NO) content in the spinal cord were measured by spectrophotometer. Verification of berberine analgesic effect by blocking N-methyl-Daspartate(NMDA) receptor: HT-22 and HEK-293 cells transfected with NMDA plasmid were randomly divided into five groups: control group, NMDA group, berberine low-dose, medium-dose, and high-dose groups(5, 10, 20 μmol/L, respectively). Except for the control group, cells were treated with NMDA(HT-22 cells: 20 mmol/L;HEK-293 cells: 50 μmol/L). After 24 h, cell viability was detected by cell counting kit-8. The molecular mechanism between berberine and the NMDA receptor was studied by molecular docking. RESULTS: Berberine 2.5 and 5.0 mg/kg could prolong the analgesic time of morphine. In acute and chronic morphine tolerance models, berberine could inhibit the decrease of MPAE and baseline latency(P < 0.05). In the established tolerance model, berberine could rapidly reverse the decreased MPAE(P < 0.05). The combination of berberine and morphine on day one could effectively inhibit the morphine-induced increase of NOS activity and NO content in the spinal cord(P < 0.05). Berberine significantly increased the cell viability of NMDA-induced nerve injury in HT-22 and HEK-293 cells(P < 0.05). Molecular docking showed that berberine binds to the receptor pocket of NMDA. CONCLUSIONS: Berberine could effectively enhance and prolong the duration of morphine analgesia and inhibit the development of morphine-induced tolerance and hyperalgesia. Furthermore, berberine has a certain neuroprotective effect, which may be related to the inhibition of NMDA activity.
基金Supported by National Natural Science Foundation of China:Differential proteomics-based research on the intervention effects,and mechanism of scraping therapy,treating lumbar disc herniation(No.81473791)Natural Science Foundation of Basic Research Program in Jiangsu Province:Proteomics research on the intervention effects,and mechanism of scraping therapy for lumbar disc herniation based on i TRAQ technology(No.BK20141464)
文摘OBJECTIVE: To investigate the analgesic effect of Gua Sha and its underlying mechanism in rats with noncompressive lumbar disk herniation induced by autologous nucleus pulposus.METHODS: A rat model of noncompressive lumbar disk herniation was established and rats were randomly divided into model group, sham group, and Gua Sha group(24 in each group). Gua Sha was performed from the 5 th day after the surgery, once every other day, 3 times for a course of treatment,and totally 3 courses. The thermal withdrawal latency was evaluated using the intelligent hot plate one day before the surgery, and on days 4(the day before the treatment), 10(the end of the firstcourse), 16(the end of the second course) and 22(the end of the third course). On days 4, 10, 16 and22, six rats in each group were picked randomly and their blood samples were drawn to assess the expression of interleukin-1β(IL-1β), interleukin-6(IL-6) and tumor necrosis factor-alpha(TNF-α).RESULTS: Compared to rats in the sham group, the application of nucleus pulposus to right L5 dorsal root ganglion induced prolonged thermal hyperalgesia, and up-regulated the expression of IL-1β,IL-6 and TNF-α in serum(P < 0.01). The therapy of Gua Sha attenuated thermal hyperalgesia potently,inhibited the expression of IL-1β, IL-6 and TNF-α in a time-dependent manner(P < 0.01). There were no significant differences in the thermal withdrawal latency and the expression of inflammatory cytokines between the sham and Gua Sha groups at the end of the treatment(P > 0.01).CONCLUSION: The current study showed that Gua Sha might alleviate thermal hyperalgesia in rats with lumbar disc herniation induced by autologous nucleus pulposus via inhibiting the expression of proinflammatory cytokins.