Previous studies have confirmed the relationship between iron-dependent ferroptosis and a peripheral nerve injury-induced neuropathic pain model.However,the role of fe rroptosis in inflammatory pain remains inconclusi...Previous studies have confirmed the relationship between iron-dependent ferroptosis and a peripheral nerve injury-induced neuropathic pain model.However,the role of fe rroptosis in inflammatory pain remains inconclusive.Therefore,we aimed to explore whether ferroptosis in the spinal cord and do rsal root ganglion contributes to complete Freund's adjuvant(CFA)-induced painful behaviors in rats.Our results revealed that various biochemical and morphological changes were associated with ferroptosis in the spinal cord and dorsal root ganglion tissues of CFA rats.These changes included iron overload,enhanced lipid peroxidation,disorders of anti-acyl-coenzyme A synthetase long-chain family member 4 and glutathione peroxidase 4 levels,and abnormal morphological changes in mitochondria.Intrathecal treatment of liproxstatin-1(a ferroptosis inhibitor)reve rsed these ferroptosis-related changes and alleviated mechanical and thermal hype rsensitivities in CFA rats.Our study demonstrated the occurrence of fe rroptosis in the spinal cord and do rsal root ganglion tissues in a rodent model of inflammatory pain and indicated that intrathecal administration of fe rroptosis inhibitors,such as liproxstatin-1,is a potential therapeutic strategy for treating inflammatory pain.展开更多
AIM To investigate the effects of herb-partitioned moxibustion(HPM) on phosphorylation of mitogen-activated extracellular signal-regulated kinase(MEK)1, extracellular signal-regulated kinase(ERK)1/2 and c AMP response...AIM To investigate the effects of herb-partitioned moxibustion(HPM) on phosphorylation of mitogen-activated extracellular signal-regulated kinase(MEK)1, extracellular signal-regulated kinase(ERK)1/2 and c AMP response element binding protein(CREB) in spinal cord of rats with chronic inflammatory visceral pain(CIVP), and to explore the central mechanism of HPM in treating CIVP.METHODS Male Sprague-Dawley rats were randomized into normal, model, HPM, sham-HPM, MEK-inhibitor and dimethyl sulfoxide(DMSO) groups. The CIVP model was established using an enema mixture of trinitrobenzene sulfonic acid and ethanol. HPM was applied at bilateral Tianshu(ST25) and Qihai(CV6) acupoints in the HPM group, while in the sham-HPM group, moxa cones and herb cakes were only placed on the same points but not ignited. The MEK-inhibitor and DMSO groups received L5-L6 intrathecal injection of U0126 and 30% DMSO, respectively. Abdominal withdrawal reflex(AWR), mechanical withdrawal threshold(MWT) and thermal withdrawal latency(TWL) were applied for the assessment of pain behavior. The colonic tissue was observed under an optical microscope after hematoxylin-eosin staining. Expression of phosphor(p)MEK1, p ERK1/2 and p CREB in rat spinal cord was detected using Western blotting. The levels of MEK, ERK and CREB m RNA in rat spinal cord were detected using real-time polymerase chain reaction. RESULTS Compared with the normal group, the AWR scores were increased significantly(P < 0.01) and the MWT and TWL scores were decreased significantly(P < 0.05) in the model, sham-HPM and DMSO groups. Compared with the model group, the AWR scores were decreased significantly(P < 0.01) and the MWT and TWL scores were increased significantly in the HPM and MEK-inhibitor groups(P < 0.05). Compared with the sham-HPM and DMSO groups, the AWR scores were decreased significantly(P < 0.01) and the MWT and TWL scores were increased significantly(P < 0.05) in the HPM and MEK-inhibitor groups. Compared with the normal group, the expression of p MEK1, p ERK1/2 and p CREB proteins and the levels of MEK, ERK and CREB m RNA in rat spinal cord were increased significantly in the model, sham-HPM and DMSO groups(P < 0.01 or < 0.05). Compared with the model group, the expression of p MEK1, p ERK1/2 and p CREB proteins and the levels of MEK, ERK and CREB m RNA in rat spinal cord were reduced significantly in the HPM and MEK-inhibitor groups(P < 0.01 or < 0.05). Compared with the sham-HPM and DMSO groups, expression of p MEK1, p ERK1/2 and p CREB proteins and the levels of MEK, ERK and CREB m RNA in rat spinal cord were reduced significantly in the HPM and MEK-inhibitor groups(P < 0.01 or < 0.05). CONCLUSION HPM down-regulates protein phosphorylation of MEK1, ERK1/2 and CREB, and m RNA expression of MEK, ERK and CREB, inhibiting activation of the MEK/ERK/CREB signaling pathway in the spinal cord of CIVP rats, which is possibly a critical central mechanism of the analgesic effect of HPM.展开更多
AIM: To evaluate intensity, localization and cofactors of pain in Crohn’s disease and ulcerative colitis patients in connection with health-related quality of life (HRQOL) and disease activity. METHODS: We reviewed a...AIM: To evaluate intensity, localization and cofactors of pain in Crohn’s disease and ulcerative colitis patients in connection with health-related quality of life (HRQOL) and disease activity. METHODS: We reviewed and analyzed the responses of 334 patients to a specifically designed questionnairebased on the short inflammatory bowel disease questionnaire (SIBDQ) and the German pain questionnaire. Pain intensity, HRQOL, Crohn’s disease activity index (CDAI) and colitis activity index (CAI) were correlated and verified on a visual analog scale (VAS). RESULTS: 87.9% of patients reported pain. Females and males reported comparable pain intensities and HRQOL. Surgery reduced pain in both genders (P = 0.023), whereas HRQOL only improved in females. Interestingly, patients on analgesics reported more pain (P = 0.003) and lower HRQOL (P = 0.039) than patients not on analgesics. A significant correlation was found in UC patients between pain intensity and HRQOL (P = 0.023) and CAI (P = 0.027), and in CD patients between HRQOL and CDAI (P = 0.0001), but not between pain intensity and CDAI (P = 0.35). No correlation was found between patients with low CDAI scores and pain intensity. CONCLUSION: Most IBD patients suffer from pain and have decreased HRQOL. Our study reinforces the need for effective individualized pain therapy in IBD patients.展开更多
This paper reviews empirical work on cognitive and social learning contributions to the etiology and treatment of illness behavior associated with functional abdominal pain and inflammatory bowel disease. A particular...This paper reviews empirical work on cognitive and social learning contributions to the etiology and treatment of illness behavior associated with functional abdominal pain and inflammatory bowel disease. A particular emphasis is placed on randomized controlled trials, the majority of which are multi-modal in orientation, incorporating elements of cognitive behavioral therapy, social learning, and relaxation. Based on this review, we offer methodological and clinical suggestions: (1) Research investigations should include adequate sample sizes, long-term follow-up assessments, and a credible, active control group. (2) Standard gastrointestinal practice should include, when appropriate, learning opportunities for patients and family members, for example, instruction regarding the encouragement of wellness behavior.展开更多
Nitric oxide(NO)/cyclic guanosine 3′,5′-monophosphate(cGMP) signaling has been shown to act as a mediator involved in pain transmission and processing. In this review, we summarize and discuss the mechanisms of the ...Nitric oxide(NO)/cyclic guanosine 3′,5′-monophosphate(cGMP) signaling has been shown to act as a mediator involved in pain transmission and processing. In this review, we summarize and discuss the mechanisms of the NO/cGMP signaling pathway involved in chronic pain, including neuropathic pain, bone cancer pain, inflammatory pain, and morphine tolerance. The main process in the NO/cGMP signaling pathway in cells involves NO activating soluble guanylate cyclase, which leads to subsequent production of cGMP. cGMP then activates cGMP-dependent protein kinase(PKG), resulting in the activation of multiple targets such as the opening of ATP-sensitive K+ channels. The activation of NO/cGMP signaling in the spinal cord evidently induces upregulation of downstream molecules, as well as reactive astrogliosis and microglial polarization which participate in the process of chronic pain. In dorsal root ganglion neurons, natriuretic peptide binds to particulate guanylyl cyclase, generating and further activating the cGMP/PKG pathway, and it also contributes to the development of chronic pain. Upregulation of multiple receptors is involved in activation of the NO/cGMP signaling pathway in various pain models. Notably the NO/cGMP signaling pathway induces expression of downstream effectors, exerting both algesic and analgesic effects in neuropathic pain and inflammatory pain. These findings suggest that activation of NO/cGMP signaling plays a constituent role in the development of chronic pain, and this signaling pathway with dual effects is an interesting and promising target for chronic pain therapy.展开更多
Objective:To compare the differences in pain mediators and inflammatory factors after percutaneous transforaminal endoscopic discectomy and traditional fenestration operation treatment of protrusion of lumbar interver...Objective:To compare the differences in pain mediators and inflammatory factors after percutaneous transforaminal endoscopic discectomy and traditional fenestration operation treatment of protrusion of lumbar intervertebral disc. Methods:80 patients with protrusion of lumbar intervertebral disc treated in our hospital between March 2013 and December 2015 were collected and divided into observation group and control group (n=40) according to randomized parallel contrast. Control group received traditional fenestration operation and observation group received percutaneous transforaminal endoscopic discectomy. Before operation and 1 week after operation, fluorescence spectrophotometry was used to determine serum pain medium levels;ELISA was used to determine pro-inflammatory factor and anti-inflammatory factor levels. Results:Before operation, differences in serum pain medium and inflammatory factor levels were not statistically significant between two groups (P>0.05). 1 week after operation, serum pain media norepinephrine (NE), dopamine (DA), 5-hydroxytryptamine (5-HT), prostaglandin E2 (PGE2) and substance P (SP) levels as well as pro-inflammatory factors interleukin-1β(IL-1β), interleukin-6 (IL-6), interleukin-18 (IL-18) and tumor necrosis factor alpha (TNF-α) levels of observation group were lower than those of control group (P<0.05) while serum anti-inflammatory factors interleukin-4 (IL-4), interleukin 10 (IL-10), soluble tumor necrosis factor receptor I (sTNF-RI) levels were higher than those of control group (P<0.05). Conclusions:Percutaneous transforaminal endoscopic discectomy can effectively treat protrusion of lumbar intervertebral disc and is more advantageous in alleviating patients’ perception of pain and reducing inflammation.展开更多
Objective:To investigate the effects of ketamine combined with lidocaine for preemptive analgesia on postoperative pain, inflammatory response and stress response in patients with cervical cancer.Methods: A total of 6...Objective:To investigate the effects of ketamine combined with lidocaine for preemptive analgesia on postoperative pain, inflammatory response and stress response in patients with cervical cancer.Methods: A total of 68 patients with cervical cancer who received radical operation in the hospital between July 2016 and May 2017 were divided into routine analgesia group (n=37) and ketamine group (n=31) according to the postoperative analgesic solution. Routine analgesia group received lidocaine for preemptive analgesia and ketamine group received ketamine combined with lidocaine for preemptive analgesia. The differences in serum levels of pain mediators, inflammatory factors and stress hormones were compared between the two groups before surgery (T0), immediately after postoperative recovery (T1) and 24h after surgery (T2).Results: At T0, there was no statistically significant difference in serum levels of pain mediators, inflammatory factors and stress hormones between the two groups. At T1 and T2, serum pain mediators SP and NPY levels of ketamine group were lower than those of routine analgesia group;inflammatory factors IL-1β, IL-6 and IL-8 levels were lower than those of routine analgesia group;stress hormones AngⅠ, AngⅡ and NE levels were lower than those of routine analgesia group.Conclusion: Ketamine combined with lidocaine for preemptive analgesia can effectively suppress the early postoperative pain mediator secretion and relieve the systemic inflammatory response and stress response in patients with cervical cancer.展开更多
Objective:To study the effect of sufentanil analgesia for hip replacement on pain mediator, stress hormone and inflammatory cytokine secretion.Methods: Patients who underwent hip replacement in People's Hospital o...Objective:To study the effect of sufentanil analgesia for hip replacement on pain mediator, stress hormone and inflammatory cytokine secretion.Methods: Patients who underwent hip replacement in People's Hospital of Dongxihu District Wuhan between August 2015 and October 2017 were selected as the research subjects and randomly divided into the sufentanil group who accepted postoperative sufentanil analgesia and the fentanyl group who accepted postoperative fentanyl analgesia. The expression levels of pain mediators and inflammatory cytokines in peripheral blood as well as the levels of pain mediators, stress hormones and inflammatory cytokines in serum were measured 1 day and 3 days after surgery.Results:Serum PGE2, SP,β-EP, GH, COR, ACTH, INS, AT-II, TNF-α and ICAM-1 levels as well as peripheral blood MKP1, p38MAPK, Caspase-1, IL-1β and IL-18 expression intensity of sufentanil group 1 day and 3 days after surgery were significantly lower than those of fentanyl group.Conclusion: Sufentanil analgesia for hip replacement can be more effective than fentanyl to reduce the secretion of pain mediators, stress hormones and inflammatory cytokines.展开更多
Objective:To study the effect of flurbiprofen axetil intervention before induction on incision pain and inflammatory stress response after orthopedic surgery.Methods: A total of 86 cases of elderly patients who underw...Objective:To study the effect of flurbiprofen axetil intervention before induction on incision pain and inflammatory stress response after orthopedic surgery.Methods: A total of 86 cases of elderly patients who underwent operative treatment of femoral neck fracture in Guangyuan Hospital of Traditional Chinese Medicine between March 2014 and December 2017 were selected as the research subjects. All patients were randomly divided into the experimental group who accepted flurbiprofen axetil intervention before induction + routine anesthesia induction and maintenance, and the control group who accepted routine anesthesia induction and maintenance, and each group included 43 cases. The pain levels of the two groups were assessed 24 h after surgery;the levels of pain mediators and inflammatory stress molecules in serum as well as the expression intensity of inflammatory stress molecules in peripheral blood were determined before surgery and 24 h after surgery.Results:24 h after surgery, serum SP, NPY, PGE2, TNF-α, IL-1β, IL-18, ACTH, COR and NE levels as well as peripheral blood NF-κB, NLRP3, Caspase-1, GLUT4 and FOXP3 expression intensity of both groups were significantly higher than those before surgery, and NRS pain score, serum SP, NPY, PGE2, TNF- , IL-1β, IL-18, ACTH, COR and NE levels as well as peripheral blood NF-κB, NLRP3, Caspase-1, GLUT4 and FOXP3 expression intensity of experimental group 24 h after surgery were significantly lower than those of control group.Conclusions:Flurbiprofen axetil intervention before induction can improve and inhibit the incision pain and inflammatory stress response after orthopedic surgery.展开更多
Objective:To study the effect of parecoxib sodium intervention before induction on incision pain and inflammatory stress response after orthopedic surgery.Methods: Patients who underwent orthopedic surgery under lumba...Objective:To study the effect of parecoxib sodium intervention before induction on incision pain and inflammatory stress response after orthopedic surgery.Methods: Patients who underwent orthopedic surgery under lumbar anesthesia combined with epidural block anesthesia in Mianyang Central Hospital between March 2015 and June 2017 were selected and divided into two groups by random number table method, Par group received parecoxib sodium intervention before induction combined with routine postoperative patient-controlled intravenous analgesia, and control group only accepted routine postoperative patient-controlled intravenous analgesia. The pain neurotransmitters, inflammatory molecules and stress molecules in serum and peripheral blood were measured before surgery as well as 1 day and 3 days after surgery.Results: Compared with pain neurotransmitters of same group before surgery, serum PGE2, 5-HT, SP, NPY levels of both groups were significantly lower whereas serum COR and GH levels and peripheral blood JAK2, STAT3, IL-1, IL-6, IFIT1, Nrf2 and HO-1 mRNA expression were significantly higher 1 day and 3 days after surgery, and serum PGE2, 5-HT, SP, NPY, COR and GH levels as well as peripheral blood JAK2, STAT3, IL-1, IL-6, IFIT1, Nrf2 and HO-1 mRNA expression of Par group 1 day and 3 days after surgery were lower than those of control group.Conclusions: Parecoxib sodium intervention before induction can reduce the incision pain and inflammatory stress response after orthopedic surgery.展开更多
Objective:To investigate the effect of fascia iliaca compartment block combined with general anesthesia on the pain and inflammatory stress mediator secretion after hip replacement. Methods: A total of 170 patients wi...Objective:To investigate the effect of fascia iliaca compartment block combined with general anesthesia on the pain and inflammatory stress mediator secretion after hip replacement. Methods: A total of 170 patients with femoral neck fracture who underwent hip replacement in this hospital between September 2015 and August 2017 were divided into the control group (n=103) who underwent routine general anesthesia and the study group (n=67) who underwent fascia iliaca compartment block combined with general anesthesia after the anesthetic solutions were reviewed. The differences in serum contents of pain mediators, inflammatory factors and stress hormones were compared between the two groups of patients immediately after surgery as well as 12 h and 24 h after surgery.Results: Immediately after surgery, there was no statistically significant difference in serum contents of pain mediators, inflammatory factors and stress hormones between the two groups. 12 h and 24 h after surgery, serum pain mediators NPY, PGE2, 5-HT,β-EP and SP contents of study group were lower than those of control group;serum inflammatory factors CRP, TNF-α and IL-1β contents were lower than those of control group;serum stress hormones Cor, CA and ACTH contents were lower than those of control group.Conclusion: fascia iliaca compartment block combined with general anesthesia can effectively reduce the postoperative pain as well as the systemic inflammatory response and stress response induced by pain in patients with hip replacement.展开更多
Objective: To study the effect of dexmedetomidine before induction on the inflammatory and stress response in transurethral resection of prostate (TURP) and the secretion of pain mediators after it. Methods: Patients ...Objective: To study the effect of dexmedetomidine before induction on the inflammatory and stress response in transurethral resection of prostate (TURP) and the secretion of pain mediators after it. Methods: Patients with benign prostatic hyperplasia who underwent TURP in Mianyang Central Hospital between June 2014 and March 2017 were selected as the research subjects and randomly divided into the Dex group who accepted dexmedetomidine combined with intraspinal anesthesia and the control group who accepted intraspinal anesthesia. The contents of inflammatory response indexes, stress response indexes and pain mediators in serum of the two groups were measured before surgery as well as 1 d and 3 d after surgery. Results: Serum NF-κB, TNF-α, IL-8, HMGB1, VCAM1, Cor, ACTH, AT-II, ALD and CRP levels of both groups of patients during surgery were higher than those before surgery, and serum CGRP, BK, SP and PGE2 levels 1 d and 3 d after surgery were higher than those before surgery;serum NF-κB, TNF-α, IL-8, HMGB1, VCAM1, Cor, ACTH, AT-II, ALD and CRP levels of Dex group of patients during surgery were lower than those of control group, and serum CGRP, BK, SP and PGE2 levels 1 day and 3 days after surgery were lower than those of control group. Conclusion: The application of dexmedetomidine before induction has inhibitory effect on the activation of inflammatory and stress response in TURP and the secretion of pain mediators after TURP.展开更多
Objective:To study the differences in pain and inflammatory stress after percutaneous transforaminal endoscope discectomy and open fenestration discectomy.Methods: Patients with lumbar intervertebral disc herniation w...Objective:To study the differences in pain and inflammatory stress after percutaneous transforaminal endoscope discectomy and open fenestration discectomy.Methods: Patients with lumbar intervertebral disc herniation who underwent surgical treatment in our hospital between January 2013 and January 2017 were selected and randomly divided into two groups: Percutaneous transforaminal endoscope discectomy (PTED) group and control group. Patients in PTED group received percutaneous transforaminal endoscope discectomy, while control group received open fenestration discectomy. Serum levels of pain substances SP, NPY, PGE2 and NGF, inflammatory mediators IFN-γ, TNF-α, IL-17 and MMP3 as well as stress response substances Cor, NE, OH-, O2- and MDA of two groups of patients were determined the same day after surgery and 3 days after surgery.Results: The same day after surgery and 3 d after surgery, serum SP, NPY, PGE2, NGF, IFN-γ, TNF-α, IL-17, MMP3, Cor, NE, OH-, O2- and MDA levels of PTED group were significantly lower than those of control group. Conclusion: Percutaneous transforaminal endoscope discectomy for lumbar intervertebral disc herniation causes less postoperative pain and inflammatory stress than open fenestration discectomy.展开更多
Objective: To study the local inflammatory stress response and pain mediator secretion after impacted wisdom tooth extraction with high-speed turbine drill combined with original luxator. Methods: Patients who receive...Objective: To study the local inflammatory stress response and pain mediator secretion after impacted wisdom tooth extraction with high-speed turbine drill combined with original luxator. Methods: Patients who received impacted wisdom tooth extraction in the First People's Hospital ofYunnan Province between March 2014 and June 2017 were selected as the research objects and randomly divided into the observation group who accepted impacted wisdom tooth extraction with high-speed turbine drill combined with original luxator and the control group who accepted impacted wisdom tooth extraction with traditional chisel. The contents of inflammatory mediators, stress mediators and pain mediators in gingival crevicular fluid were measured before surgery and 3 days after surgery. Results: Three days after surgery, PTX3, ICAM1, MPO, PGE2, PPARγ, ROS, MDA, 5-HT, CGRP, SP, Gal and ATP contents in gingival crevicular fluid of both groups were higher than those before surgery whereas GPx and T-AOC contents were significantly lower than those before surgery, and PTX3, ICAM1, MPO, PGE2, PPARγ, ROS, MDA, 5-HT, CGRP, SP, Gal and ATP contents in gingival crevicular fluid of observation group were lower than those of control group whereas GPx and T-AOC contents were significantly higher than those of control group. Conclusions: The impacted wisdom tooth extraction with high-speed turbine drill combined with original luxator can reduce the local inflammatory stress response and inhibit the secretion of pain mediators.展开更多
Objective:To study the effect of dezocine combined with sufentanil patient-controlled intravenous analgesia on general pain and inflammatory mediators after laparoscopic hepatectomy.Methods: A total of 68 patients wit...Objective:To study the effect of dezocine combined with sufentanil patient-controlled intravenous analgesia on general pain and inflammatory mediators after laparoscopic hepatectomy.Methods: A total of 68 patients with primary liver cancer who received laparoscopic surgical treatment in our hospital between July 2014 and December 2016 were collected, the therapies were reviewed, and then patients were divided into the control group (n=35) who received sufentanil PCIA and the observation group (n=33) who received dezocine combined with sufentanil PCIA. Differences in serum levels of pain mediators, acute phase proteins and interleukins were compared between the two groups of patients before and after operation.Results: Before operation, the differences in serum levels of pain mediators, acute phase proteins and interleukins were not statistically significant between the two groups of patients. 6h after operation, serum pain mediators SP, NPY, DA and NE levels in observation group were lower than those in control group;acute phase proteins CRP, HP, CER and AAG levels were lower than those in control group;interleukins IL-1β, IL-6 and IL-8 levels were lower than those in control group.Conclusion: Dezocine combined with sufentanil PCIA after laparoscopic hepatectomy is effective in reducing the early postoperative pain mediator levels and relieving systemic inflammatory response.展开更多
基金supported by the Basic and Applied Basic Research Foundation of Guangdong Province,No.2021A1515220081(to XL)。
文摘Previous studies have confirmed the relationship between iron-dependent ferroptosis and a peripheral nerve injury-induced neuropathic pain model.However,the role of fe rroptosis in inflammatory pain remains inconclusive.Therefore,we aimed to explore whether ferroptosis in the spinal cord and do rsal root ganglion contributes to complete Freund's adjuvant(CFA)-induced painful behaviors in rats.Our results revealed that various biochemical and morphological changes were associated with ferroptosis in the spinal cord and dorsal root ganglion tissues of CFA rats.These changes included iron overload,enhanced lipid peroxidation,disorders of anti-acyl-coenzyme A synthetase long-chain family member 4 and glutathione peroxidase 4 levels,and abnormal morphological changes in mitochondria.Intrathecal treatment of liproxstatin-1(a ferroptosis inhibitor)reve rsed these ferroptosis-related changes and alleviated mechanical and thermal hype rsensitivities in CFA rats.Our study demonstrated the occurrence of fe rroptosis in the spinal cord and do rsal root ganglion tissues in a rodent model of inflammatory pain and indicated that intrathecal administration of fe rroptosis inhibitors,such as liproxstatin-1,is a potential therapeutic strategy for treating inflammatory pain.
基金Supported by National Natural Science Foundation of China,No.81273843 and No.81674073National Key Basic Research Program of China(973 Program)+1 种基金No.2015CB554501Project of Shanghai Municipal Commission of Health and Family Planning,No.20144Y0153 and No.2017BR047
文摘AIM To investigate the effects of herb-partitioned moxibustion(HPM) on phosphorylation of mitogen-activated extracellular signal-regulated kinase(MEK)1, extracellular signal-regulated kinase(ERK)1/2 and c AMP response element binding protein(CREB) in spinal cord of rats with chronic inflammatory visceral pain(CIVP), and to explore the central mechanism of HPM in treating CIVP.METHODS Male Sprague-Dawley rats were randomized into normal, model, HPM, sham-HPM, MEK-inhibitor and dimethyl sulfoxide(DMSO) groups. The CIVP model was established using an enema mixture of trinitrobenzene sulfonic acid and ethanol. HPM was applied at bilateral Tianshu(ST25) and Qihai(CV6) acupoints in the HPM group, while in the sham-HPM group, moxa cones and herb cakes were only placed on the same points but not ignited. The MEK-inhibitor and DMSO groups received L5-L6 intrathecal injection of U0126 and 30% DMSO, respectively. Abdominal withdrawal reflex(AWR), mechanical withdrawal threshold(MWT) and thermal withdrawal latency(TWL) were applied for the assessment of pain behavior. The colonic tissue was observed under an optical microscope after hematoxylin-eosin staining. Expression of phosphor(p)MEK1, p ERK1/2 and p CREB in rat spinal cord was detected using Western blotting. The levels of MEK, ERK and CREB m RNA in rat spinal cord were detected using real-time polymerase chain reaction. RESULTS Compared with the normal group, the AWR scores were increased significantly(P < 0.01) and the MWT and TWL scores were decreased significantly(P < 0.05) in the model, sham-HPM and DMSO groups. Compared with the model group, the AWR scores were decreased significantly(P < 0.01) and the MWT and TWL scores were increased significantly in the HPM and MEK-inhibitor groups(P < 0.05). Compared with the sham-HPM and DMSO groups, the AWR scores were decreased significantly(P < 0.01) and the MWT and TWL scores were increased significantly(P < 0.05) in the HPM and MEK-inhibitor groups. Compared with the normal group, the expression of p MEK1, p ERK1/2 and p CREB proteins and the levels of MEK, ERK and CREB m RNA in rat spinal cord were increased significantly in the model, sham-HPM and DMSO groups(P < 0.01 or < 0.05). Compared with the model group, the expression of p MEK1, p ERK1/2 and p CREB proteins and the levels of MEK, ERK and CREB m RNA in rat spinal cord were reduced significantly in the HPM and MEK-inhibitor groups(P < 0.01 or < 0.05). Compared with the sham-HPM and DMSO groups, expression of p MEK1, p ERK1/2 and p CREB proteins and the levels of MEK, ERK and CREB m RNA in rat spinal cord were reduced significantly in the HPM and MEK-inhibitor groups(P < 0.01 or < 0.05). CONCLUSION HPM down-regulates protein phosphorylation of MEK1, ERK1/2 and CREB, and m RNA expression of MEK, ERK and CREB, inhibiting activation of the MEK/ERK/CREB signaling pathway in the spinal cord of CIVP rats, which is possibly a critical central mechanism of the analgesic effect of HPM.
文摘AIM: To evaluate intensity, localization and cofactors of pain in Crohn’s disease and ulcerative colitis patients in connection with health-related quality of life (HRQOL) and disease activity. METHODS: We reviewed and analyzed the responses of 334 patients to a specifically designed questionnairebased on the short inflammatory bowel disease questionnaire (SIBDQ) and the German pain questionnaire. Pain intensity, HRQOL, Crohn’s disease activity index (CDAI) and colitis activity index (CAI) were correlated and verified on a visual analog scale (VAS). RESULTS: 87.9% of patients reported pain. Females and males reported comparable pain intensities and HRQOL. Surgery reduced pain in both genders (P = 0.023), whereas HRQOL only improved in females. Interestingly, patients on analgesics reported more pain (P = 0.003) and lower HRQOL (P = 0.039) than patients not on analgesics. A significant correlation was found in UC patients between pain intensity and HRQOL (P = 0.023) and CAI (P = 0.027), and in CD patients between HRQOL and CDAI (P = 0.0001), but not between pain intensity and CDAI (P = 0.35). No correlation was found between patients with low CDAI scores and pain intensity. CONCLUSION: Most IBD patients suffer from pain and have decreased HRQOL. Our study reinforces the need for effective individualized pain therapy in IBD patients.
基金NIH grants R01 HD36069-06 awarded to Dr.Levy and R24 067674 awarded to Dr.Whitehead
文摘This paper reviews empirical work on cognitive and social learning contributions to the etiology and treatment of illness behavior associated with functional abdominal pain and inflammatory bowel disease. A particular emphasis is placed on randomized controlled trials, the majority of which are multi-modal in orientation, incorporating elements of cognitive behavioral therapy, social learning, and relaxation. Based on this review, we offer methodological and clinical suggestions: (1) Research investigations should include adequate sample sizes, long-term follow-up assessments, and a credible, active control group. (2) Standard gastrointestinal practice should include, when appropriate, learning opportunities for patients and family members, for example, instruction regarding the encouragement of wellness behavior.
基金supported by the National Natural Science Foundation of China,Nos. 82071556 (to WM), 81873793 (to WM), 82001198 (to YQZ), 82101310 (to DQL)the National Key Research and Development Program of China,No. 2020YFC2005300 (to WM)。
文摘Nitric oxide(NO)/cyclic guanosine 3′,5′-monophosphate(cGMP) signaling has been shown to act as a mediator involved in pain transmission and processing. In this review, we summarize and discuss the mechanisms of the NO/cGMP signaling pathway involved in chronic pain, including neuropathic pain, bone cancer pain, inflammatory pain, and morphine tolerance. The main process in the NO/cGMP signaling pathway in cells involves NO activating soluble guanylate cyclase, which leads to subsequent production of cGMP. cGMP then activates cGMP-dependent protein kinase(PKG), resulting in the activation of multiple targets such as the opening of ATP-sensitive K+ channels. The activation of NO/cGMP signaling in the spinal cord evidently induces upregulation of downstream molecules, as well as reactive astrogliosis and microglial polarization which participate in the process of chronic pain. In dorsal root ganglion neurons, natriuretic peptide binds to particulate guanylyl cyclase, generating and further activating the cGMP/PKG pathway, and it also contributes to the development of chronic pain. Upregulation of multiple receptors is involved in activation of the NO/cGMP signaling pathway in various pain models. Notably the NO/cGMP signaling pathway induces expression of downstream effectors, exerting both algesic and analgesic effects in neuropathic pain and inflammatory pain. These findings suggest that activation of NO/cGMP signaling plays a constituent role in the development of chronic pain, and this signaling pathway with dual effects is an interesting and promising target for chronic pain therapy.
基金Research Project of Sichuan Provincial Health Department(No:130914).
文摘Objective:To compare the differences in pain mediators and inflammatory factors after percutaneous transforaminal endoscopic discectomy and traditional fenestration operation treatment of protrusion of lumbar intervertebral disc. Methods:80 patients with protrusion of lumbar intervertebral disc treated in our hospital between March 2013 and December 2015 were collected and divided into observation group and control group (n=40) according to randomized parallel contrast. Control group received traditional fenestration operation and observation group received percutaneous transforaminal endoscopic discectomy. Before operation and 1 week after operation, fluorescence spectrophotometry was used to determine serum pain medium levels;ELISA was used to determine pro-inflammatory factor and anti-inflammatory factor levels. Results:Before operation, differences in serum pain medium and inflammatory factor levels were not statistically significant between two groups (P>0.05). 1 week after operation, serum pain media norepinephrine (NE), dopamine (DA), 5-hydroxytryptamine (5-HT), prostaglandin E2 (PGE2) and substance P (SP) levels as well as pro-inflammatory factors interleukin-1β(IL-1β), interleukin-6 (IL-6), interleukin-18 (IL-18) and tumor necrosis factor alpha (TNF-α) levels of observation group were lower than those of control group (P<0.05) while serum anti-inflammatory factors interleukin-4 (IL-4), interleukin 10 (IL-10), soluble tumor necrosis factor receptor I (sTNF-RI) levels were higher than those of control group (P<0.05). Conclusions:Percutaneous transforaminal endoscopic discectomy can effectively treat protrusion of lumbar intervertebral disc and is more advantageous in alleviating patients’ perception of pain and reducing inflammation.
文摘Objective:To investigate the effects of ketamine combined with lidocaine for preemptive analgesia on postoperative pain, inflammatory response and stress response in patients with cervical cancer.Methods: A total of 68 patients with cervical cancer who received radical operation in the hospital between July 2016 and May 2017 were divided into routine analgesia group (n=37) and ketamine group (n=31) according to the postoperative analgesic solution. Routine analgesia group received lidocaine for preemptive analgesia and ketamine group received ketamine combined with lidocaine for preemptive analgesia. The differences in serum levels of pain mediators, inflammatory factors and stress hormones were compared between the two groups before surgery (T0), immediately after postoperative recovery (T1) and 24h after surgery (T2).Results: At T0, there was no statistically significant difference in serum levels of pain mediators, inflammatory factors and stress hormones between the two groups. At T1 and T2, serum pain mediators SP and NPY levels of ketamine group were lower than those of routine analgesia group;inflammatory factors IL-1β, IL-6 and IL-8 levels were lower than those of routine analgesia group;stress hormones AngⅠ, AngⅡ and NE levels were lower than those of routine analgesia group.Conclusion: Ketamine combined with lidocaine for preemptive analgesia can effectively suppress the early postoperative pain mediator secretion and relieve the systemic inflammatory response and stress response in patients with cervical cancer.
文摘Objective:To study the effect of sufentanil analgesia for hip replacement on pain mediator, stress hormone and inflammatory cytokine secretion.Methods: Patients who underwent hip replacement in People's Hospital of Dongxihu District Wuhan between August 2015 and October 2017 were selected as the research subjects and randomly divided into the sufentanil group who accepted postoperative sufentanil analgesia and the fentanyl group who accepted postoperative fentanyl analgesia. The expression levels of pain mediators and inflammatory cytokines in peripheral blood as well as the levels of pain mediators, stress hormones and inflammatory cytokines in serum were measured 1 day and 3 days after surgery.Results:Serum PGE2, SP,β-EP, GH, COR, ACTH, INS, AT-II, TNF-α and ICAM-1 levels as well as peripheral blood MKP1, p38MAPK, Caspase-1, IL-1β and IL-18 expression intensity of sufentanil group 1 day and 3 days after surgery were significantly lower than those of fentanyl group.Conclusion: Sufentanil analgesia for hip replacement can be more effective than fentanyl to reduce the secretion of pain mediators, stress hormones and inflammatory cytokines.
文摘Objective:To study the effect of flurbiprofen axetil intervention before induction on incision pain and inflammatory stress response after orthopedic surgery.Methods: A total of 86 cases of elderly patients who underwent operative treatment of femoral neck fracture in Guangyuan Hospital of Traditional Chinese Medicine between March 2014 and December 2017 were selected as the research subjects. All patients were randomly divided into the experimental group who accepted flurbiprofen axetil intervention before induction + routine anesthesia induction and maintenance, and the control group who accepted routine anesthesia induction and maintenance, and each group included 43 cases. The pain levels of the two groups were assessed 24 h after surgery;the levels of pain mediators and inflammatory stress molecules in serum as well as the expression intensity of inflammatory stress molecules in peripheral blood were determined before surgery and 24 h after surgery.Results:24 h after surgery, serum SP, NPY, PGE2, TNF-α, IL-1β, IL-18, ACTH, COR and NE levels as well as peripheral blood NF-κB, NLRP3, Caspase-1, GLUT4 and FOXP3 expression intensity of both groups were significantly higher than those before surgery, and NRS pain score, serum SP, NPY, PGE2, TNF- , IL-1β, IL-18, ACTH, COR and NE levels as well as peripheral blood NF-κB, NLRP3, Caspase-1, GLUT4 and FOXP3 expression intensity of experimental group 24 h after surgery were significantly lower than those of control group.Conclusions:Flurbiprofen axetil intervention before induction can improve and inhibit the incision pain and inflammatory stress response after orthopedic surgery.
文摘Objective:To study the effect of parecoxib sodium intervention before induction on incision pain and inflammatory stress response after orthopedic surgery.Methods: Patients who underwent orthopedic surgery under lumbar anesthesia combined with epidural block anesthesia in Mianyang Central Hospital between March 2015 and June 2017 were selected and divided into two groups by random number table method, Par group received parecoxib sodium intervention before induction combined with routine postoperative patient-controlled intravenous analgesia, and control group only accepted routine postoperative patient-controlled intravenous analgesia. The pain neurotransmitters, inflammatory molecules and stress molecules in serum and peripheral blood were measured before surgery as well as 1 day and 3 days after surgery.Results: Compared with pain neurotransmitters of same group before surgery, serum PGE2, 5-HT, SP, NPY levels of both groups were significantly lower whereas serum COR and GH levels and peripheral blood JAK2, STAT3, IL-1, IL-6, IFIT1, Nrf2 and HO-1 mRNA expression were significantly higher 1 day and 3 days after surgery, and serum PGE2, 5-HT, SP, NPY, COR and GH levels as well as peripheral blood JAK2, STAT3, IL-1, IL-6, IFIT1, Nrf2 and HO-1 mRNA expression of Par group 1 day and 3 days after surgery were lower than those of control group.Conclusions: Parecoxib sodium intervention before induction can reduce the incision pain and inflammatory stress response after orthopedic surgery.
文摘Objective:To investigate the effect of fascia iliaca compartment block combined with general anesthesia on the pain and inflammatory stress mediator secretion after hip replacement. Methods: A total of 170 patients with femoral neck fracture who underwent hip replacement in this hospital between September 2015 and August 2017 were divided into the control group (n=103) who underwent routine general anesthesia and the study group (n=67) who underwent fascia iliaca compartment block combined with general anesthesia after the anesthetic solutions were reviewed. The differences in serum contents of pain mediators, inflammatory factors and stress hormones were compared between the two groups of patients immediately after surgery as well as 12 h and 24 h after surgery.Results: Immediately after surgery, there was no statistically significant difference in serum contents of pain mediators, inflammatory factors and stress hormones between the two groups. 12 h and 24 h after surgery, serum pain mediators NPY, PGE2, 5-HT,β-EP and SP contents of study group were lower than those of control group;serum inflammatory factors CRP, TNF-α and IL-1β contents were lower than those of control group;serum stress hormones Cor, CA and ACTH contents were lower than those of control group.Conclusion: fascia iliaca compartment block combined with general anesthesia can effectively reduce the postoperative pain as well as the systemic inflammatory response and stress response induced by pain in patients with hip replacement.
文摘Objective: To study the effect of dexmedetomidine before induction on the inflammatory and stress response in transurethral resection of prostate (TURP) and the secretion of pain mediators after it. Methods: Patients with benign prostatic hyperplasia who underwent TURP in Mianyang Central Hospital between June 2014 and March 2017 were selected as the research subjects and randomly divided into the Dex group who accepted dexmedetomidine combined with intraspinal anesthesia and the control group who accepted intraspinal anesthesia. The contents of inflammatory response indexes, stress response indexes and pain mediators in serum of the two groups were measured before surgery as well as 1 d and 3 d after surgery. Results: Serum NF-κB, TNF-α, IL-8, HMGB1, VCAM1, Cor, ACTH, AT-II, ALD and CRP levels of both groups of patients during surgery were higher than those before surgery, and serum CGRP, BK, SP and PGE2 levels 1 d and 3 d after surgery were higher than those before surgery;serum NF-κB, TNF-α, IL-8, HMGB1, VCAM1, Cor, ACTH, AT-II, ALD and CRP levels of Dex group of patients during surgery were lower than those of control group, and serum CGRP, BK, SP and PGE2 levels 1 day and 3 days after surgery were lower than those of control group. Conclusion: The application of dexmedetomidine before induction has inhibitory effect on the activation of inflammatory and stress response in TURP and the secretion of pain mediators after TURP.
文摘Objective:To study the differences in pain and inflammatory stress after percutaneous transforaminal endoscope discectomy and open fenestration discectomy.Methods: Patients with lumbar intervertebral disc herniation who underwent surgical treatment in our hospital between January 2013 and January 2017 were selected and randomly divided into two groups: Percutaneous transforaminal endoscope discectomy (PTED) group and control group. Patients in PTED group received percutaneous transforaminal endoscope discectomy, while control group received open fenestration discectomy. Serum levels of pain substances SP, NPY, PGE2 and NGF, inflammatory mediators IFN-γ, TNF-α, IL-17 and MMP3 as well as stress response substances Cor, NE, OH-, O2- and MDA of two groups of patients were determined the same day after surgery and 3 days after surgery.Results: The same day after surgery and 3 d after surgery, serum SP, NPY, PGE2, NGF, IFN-γ, TNF-α, IL-17, MMP3, Cor, NE, OH-, O2- and MDA levels of PTED group were significantly lower than those of control group. Conclusion: Percutaneous transforaminal endoscope discectomy for lumbar intervertebral disc herniation causes less postoperative pain and inflammatory stress than open fenestration discectomy.
文摘Objective: To study the local inflammatory stress response and pain mediator secretion after impacted wisdom tooth extraction with high-speed turbine drill combined with original luxator. Methods: Patients who received impacted wisdom tooth extraction in the First People's Hospital ofYunnan Province between March 2014 and June 2017 were selected as the research objects and randomly divided into the observation group who accepted impacted wisdom tooth extraction with high-speed turbine drill combined with original luxator and the control group who accepted impacted wisdom tooth extraction with traditional chisel. The contents of inflammatory mediators, stress mediators and pain mediators in gingival crevicular fluid were measured before surgery and 3 days after surgery. Results: Three days after surgery, PTX3, ICAM1, MPO, PGE2, PPARγ, ROS, MDA, 5-HT, CGRP, SP, Gal and ATP contents in gingival crevicular fluid of both groups were higher than those before surgery whereas GPx and T-AOC contents were significantly lower than those before surgery, and PTX3, ICAM1, MPO, PGE2, PPARγ, ROS, MDA, 5-HT, CGRP, SP, Gal and ATP contents in gingival crevicular fluid of observation group were lower than those of control group whereas GPx and T-AOC contents were significantly higher than those of control group. Conclusions: The impacted wisdom tooth extraction with high-speed turbine drill combined with original luxator can reduce the local inflammatory stress response and inhibit the secretion of pain mediators.
文摘Objective:To study the effect of dezocine combined with sufentanil patient-controlled intravenous analgesia on general pain and inflammatory mediators after laparoscopic hepatectomy.Methods: A total of 68 patients with primary liver cancer who received laparoscopic surgical treatment in our hospital between July 2014 and December 2016 were collected, the therapies were reviewed, and then patients were divided into the control group (n=35) who received sufentanil PCIA and the observation group (n=33) who received dezocine combined with sufentanil PCIA. Differences in serum levels of pain mediators, acute phase proteins and interleukins were compared between the two groups of patients before and after operation.Results: Before operation, the differences in serum levels of pain mediators, acute phase proteins and interleukins were not statistically significant between the two groups of patients. 6h after operation, serum pain mediators SP, NPY, DA and NE levels in observation group were lower than those in control group;acute phase proteins CRP, HP, CER and AAG levels were lower than those in control group;interleukins IL-1β, IL-6 and IL-8 levels were lower than those in control group.Conclusion: Dezocine combined with sufentanil PCIA after laparoscopic hepatectomy is effective in reducing the early postoperative pain mediator levels and relieving systemic inflammatory response.