Neuropathic pain was produced by chronic constriction injury of the sciatic nerve in rats. Behaviora tests showed that the thresholds for thermal and mechanical hyperalgesia were significantly reduced in neuropathic p...Neuropathic pain was produced by chronic constriction injury of the sciatic nerve in rats. Behaviora tests showed that the thresholds for thermal and mechanical hyperalgesia were significantly reduced in neuropathic pain rats 3 28 days following model induction. The results of immunohistochemistry, western blot assays and reverse transcription-PCR showed that Nay1.7 protein and mRNA expression was significantly increased in the injured dorsal root ganglia. These findings indicated that Nay1.7 might play an important role in the model of chronic neuropathic pain展开更多
The use of iodine-125 （L251） in cancer treatment has been shown to relieve patients＇ pain. Consid- ering dorsal root ganglia are critical for neural transmission between the peripheral and central nervous systems, ...The use of iodine-125 （L251） in cancer treatment has been shown to relieve patients＇ pain. Consid- ering dorsal root ganglia are critical for neural transmission between the peripheral and central nervous systems, we assumed that 125I could be implanted into rat dorsal root ganglia to provide relief for neuropathic pain. 125I seeds with different radioactivity （0, 14.8, 29.6 MBq） were im- planted separately through L4-5 and L5-6 intervertebral foramen into the vicinity of the L5 dorsal root ganglion, von Frey hair results demonstrated the mechanical pain threshold was elevated after implanting 125I seeds from the high radioactivity group. Transmission electron microscopy revealed that nuclear membrane shrinkage, nucleolar margination, widespread mitochondrial swelling, partial vacuolization, lysosome increase, and partial endoplasmic reticulum dilation were visible at 1,440 hours in the low radioactivity group and at 336 hours in the high radio- activity group. Abundant nuclear membrane shrinkage, partial fuzzy nuclear membrane and endoplasmic reticulum necrosis were observed at 1,440 hours in the high radioactivity group. No significant difference in combined behavioral scores was detected between preoperation and postoperation in the low and high radioactivity groups. These results suggested that the mechan- ical pain threshold was elevated after implanting 125I seeds without influencing motor functions of the hind limb, although cell injury was present.展开更多
Along with the development of economy and society, type 2 diabetic mellitus(T2DM) has become one of the most common diseases at the global level. As one of the complications of T2 DM, diabetic neuropathic pain(DNP) st...Along with the development of economy and society, type 2 diabetic mellitus(T2DM) has become one of the most common diseases at the global level. As one of the complications of T2 DM, diabetic neuropathic pain(DNP) stubbornly and chronically affects the health and life of human beings. In the pain field, dorsal root ganglion(DRG) is generally considered as the first stage of the sensory pathway where the hyperexcitability of injured neurons is associated with different kinds of peripheral neuropathic pains. The abnormal electrophysiology is mainly due to the changed properties of voltage-gated sodium channels(VGSCs) and the increased sodium currents(INa). Curcumin is an active ingredient extracted from turmeric and has been demonstrated to ameliorate T2 DM and its various complications including DNP effectively. The present study demonstrates that the INa of small-sized DRG neurons are significantly increased with the abnormal electrophysiological characteristics of VGSCs in type 2 diabetic neuropathic pain rats. And these abnormalities can be ameliorated efficaciously by a period of treatment with curcumin.展开更多
Some pelvic pain syndromes are very resistant to medical treatment. Several studies have demonstrated that sacral neuromodulation, which has been successfully used for the treatment of bladder dysfunction, incontinenc...Some pelvic pain syndromes are very resistant to medical treatment. Several studies have demonstrated that sacral neuromodulation, which has been successfully used for the treatment of bladder dysfunction, incontinence, urinary retention and urinary frequency [1]-[3], can be successfully used for the treatment of chronic pelvic pain [4]-[7]. Several studies have also demonstrated significant involvement of dorsal column pathways in the transmission of visceral pelvic pain [8] and the successful use of spinal cord stimulation for the treatment of chronic pelvic pain [9]. We report three cases of severe chronic pelvic pain that failed conservative treatment modalities. Placement of a combined sacral nerve roots stimulator and a low thoracic spinal cord stimulator resulted in a significant pain relief and improvement in daily life activities. We believe that this combination may help patients suffering from chronic pelvic pain resistant to medical management.展开更多
Approximately 50-70% of patients experience incision-induced mechanical nociception after sur- gery. However, the mechanism underlying incision-induced mechanical nociception is still unclear. Interleukin-10 and brain...Approximately 50-70% of patients experience incision-induced mechanical nociception after sur- gery. However, the mechanism underlying incision-induced mechanical nociception is still unclear. Interleukin-10 and brain-derived neurotrophic factor are important pain mediators, but whether in- terleukin-10 and brain-derived neurotrophic factor are involved in incision-induced mechanical no- ciception remains uncertain. In this study, forty rats were divided randomly into the incision surgery （n = 32） and sham surgery （n = 8） groups. Plantar incision on the central part of left hind paw was performed under anesthesia in rats from the surgery group. Rats in the sham surgery group re- ceived anesthesia, but not an incision. Yon Frey test results showed that, compared with the sham surgery group, incision surgery decreased the withdrawal threshold of rats at 0.5, 3, 6 and 24 hours after incision. Immunofluorescence staining in the dorsal root ganglia of the spinal cord （L3-5） showed that interleukin-10 and brain-derived neurotrophic factor were expressed mainly on small- and medium-sized neurons （diameter 〈 20 pm and 20-40 pm） and satellite cells in the dorsal root ganglia of the spinal cord （L3-5） in the sham surgery group. By contrast, in the surgery group, high expression of interleukin-10 and brain-derived neurotrophic factor appeared in large-sized neurons （diameter 〉 40 pm） at 6 and 24 hours after incision surgery, which corresponded to the decreased mechanical withdrawal threshold of rats in the surgery group. These experimental findings suggest that expression pattern shift of interleukin-10 and brain-derived neurotrophic factor induced by inci- sion surgery in dorsal root ganglia of rats was closely involved in lowering the threshold to me- chanical stimulus in the hind paw following incision surgery. Pain-related mediators induced by in- cision surgery in dorsal root ganglia of rats possibly underlie mechanical nociception in ipsilateral hind paws.展开更多
BACKGROUND： Inflammatory responses in injured nerves have been recognized as important factors for initially sensitizing nociceptive neurons. Cyclooxygenase （COX） is the rate-limiting enzyme in prostaglandin synthe...BACKGROUND： Inflammatory responses in injured nerves have been recognized as important factors for initially sensitizing nociceptive neurons. Cyclooxygenase （COX） is the rate-limiting enzyme in prostaglandin synthesis, and COX-2 inhibitor is involved in mechanisms of analgesia and anti-inflammation. OBJECTIVE： To investigate the effects of COX-2 inhibitor on thermal and mechanical hyperalgesia, as well as expression of growth associated protein 43 （GAP-43） and nerve growth factor （NGF） in dorsal root ganglion, in a rat model of neuropathic pain due to chronic constriction injury. DESIGN, TIME AND SETTING： A randomized, controlled, comparison study that was performed at the Surgical Department and Pathological Laboratory, Second Affiliated Hospital of Shantou University Medical College from September 2006 to September 2007. MATERIALS： COX-2 inhibitor, Iornoxicam, was purchased from Nycomed Pharmaceutical （Austria）; rabbit anti-GAP-43, and rabbit anti-NGF polyclonal antibodies were purchased from Boster, Wuhan, China. METHODS： A total of 50 adult, Wistar rats were randomly assigned to four groups： normal control （n = 5）, model （n = 15）, normal saline control （n = 15）, and Iornoxicam treatment （n =15）. With exception of the control group, the sciatic nerve of all rats was loosely ligated to establish a model of chronic constriction injury. The model rats were divided into three subgroups according to varying post-operative survival periods： 3, 7 and 14 days （n = 5）, respectively. Rats in the Iornoxicam treatment group were intraperitoneally injected with 1.3 mg/kg lornoxicam every 12 hours throughout the entire experimental procedure. Rats in the normal saline control group were intraperitoneally injected with 1.3 mL/kg saline. MAIN OUTCOME MEASURES： Immunohistochemistry revealed expression of GAP-43 and NGF in the L5 dorsal root ganglions. Mechanical withdrawal threshold and thermal withdrawal latency were used to observe neurological behavioral changes in rats. RESULTS： The relative gray values of GAP-43- and NGF-positive neurons in the model group were remarkably increased compared with the normal control rats （P 〈 0.01）, while the relative gray values in the Iomoxicam treatment group were significantly less than the model and normal saline control groups （P 〈 0.01）. Mechanical withdrawal threshold and thermal withdrawal latency gradually decreased with increasing injury time in the model, normal saline control, and Iornoxicam treatment groups, and were significantly less than the normal control group （P 〈 0.05）. In addition, mechanical withdrawal threshold and thermal withdrawal latency were significantly greater in the Iornoxicam treatment group compared with the model and normal saline control groups （P 〈 0.05）. CONCLUSION： Intraperitoneal injection of the COX-2 inhibitor Iornoxicam attenuated mechanical and thermal hyperalgesia induced by sciatic nerve chronic constriction injury and inhibited the increased expression of GAP-43 and NGF.展开更多
基金This study was supported by the National Natural Science Foundation of China(The mechanism of Na_v 1.7 (encoded by SCN9A gene) activated by chronic neuropathic pain and the experimental study of analgesia by SCN9A RNAi), No.81171059
文摘Neuropathic pain was produced by chronic constriction injury of the sciatic nerve in rats. Behaviora tests showed that the thresholds for thermal and mechanical hyperalgesia were significantly reduced in neuropathic pain rats 3 28 days following model induction. The results of immunohistochemistry, western blot assays and reverse transcription-PCR showed that Nay1.7 protein and mRNA expression was significantly increased in the injured dorsal root ganglia. These findings indicated that Nay1.7 might play an important role in the model of chronic neuropathic pain
基金supported by Technology Foundation for Selected Overseas Chinese Scholar,Ministry of Personnel of China,2011,Ren 1144
文摘The use of iodine-125 （L251） in cancer treatment has been shown to relieve patients＇ pain. Consid- ering dorsal root ganglia are critical for neural transmission between the peripheral and central nervous systems, we assumed that 125I could be implanted into rat dorsal root ganglia to provide relief for neuropathic pain. 125I seeds with different radioactivity （0, 14.8, 29.6 MBq） were im- planted separately through L4-5 and L5-6 intervertebral foramen into the vicinity of the L5 dorsal root ganglion, von Frey hair results demonstrated the mechanical pain threshold was elevated after implanting 125I seeds from the high radioactivity group. Transmission electron microscopy revealed that nuclear membrane shrinkage, nucleolar margination, widespread mitochondrial swelling, partial vacuolization, lysosome increase, and partial endoplasmic reticulum dilation were visible at 1,440 hours in the low radioactivity group and at 336 hours in the high radio- activity group. Abundant nuclear membrane shrinkage, partial fuzzy nuclear membrane and endoplasmic reticulum necrosis were observed at 1,440 hours in the high radioactivity group. No significant difference in combined behavioral scores was detected between preoperation and postoperation in the low and high radioactivity groups. These results suggested that the mechan- ical pain threshold was elevated after implanting 125I seeds without influencing motor functions of the hind limb, although cell injury was present.
基金supported by a grant from the National Natural Science Foundation of China(No.81073125)Natural Science Foundation of Zhejiang Province(Y2090252)
文摘Along with the development of economy and society, type 2 diabetic mellitus(T2DM) has become one of the most common diseases at the global level. As one of the complications of T2 DM, diabetic neuropathic pain(DNP) stubbornly and chronically affects the health and life of human beings. In the pain field, dorsal root ganglion(DRG) is generally considered as the first stage of the sensory pathway where the hyperexcitability of injured neurons is associated with different kinds of peripheral neuropathic pains. The abnormal electrophysiology is mainly due to the changed properties of voltage-gated sodium channels(VGSCs) and the increased sodium currents(INa). Curcumin is an active ingredient extracted from turmeric and has been demonstrated to ameliorate T2 DM and its various complications including DNP effectively. The present study demonstrates that the INa of small-sized DRG neurons are significantly increased with the abnormal electrophysiological characteristics of VGSCs in type 2 diabetic neuropathic pain rats. And these abnormalities can be ameliorated efficaciously by a period of treatment with curcumin.
文摘Some pelvic pain syndromes are very resistant to medical treatment. Several studies have demonstrated that sacral neuromodulation, which has been successfully used for the treatment of bladder dysfunction, incontinence, urinary retention and urinary frequency [1]-[3], can be successfully used for the treatment of chronic pelvic pain [4]-[7]. Several studies have also demonstrated significant involvement of dorsal column pathways in the transmission of visceral pelvic pain [8] and the successful use of spinal cord stimulation for the treatment of chronic pelvic pain [9]. We report three cases of severe chronic pelvic pain that failed conservative treatment modalities. Placement of a combined sacral nerve roots stimulator and a low thoracic spinal cord stimulator resulted in a significant pain relief and improvement in daily life activities. We believe that this combination may help patients suffering from chronic pelvic pain resistant to medical management.
基金supported by the Science and Technology Project of Hunan Province,No.2010SK3119125 Talents Project of 3~(rd) Xiangya Hospital,Central South University in China
文摘Approximately 50-70% of patients experience incision-induced mechanical nociception after sur- gery. However, the mechanism underlying incision-induced mechanical nociception is still unclear. Interleukin-10 and brain-derived neurotrophic factor are important pain mediators, but whether in- terleukin-10 and brain-derived neurotrophic factor are involved in incision-induced mechanical no- ciception remains uncertain. In this study, forty rats were divided randomly into the incision surgery （n = 32） and sham surgery （n = 8） groups. Plantar incision on the central part of left hind paw was performed under anesthesia in rats from the surgery group. Rats in the sham surgery group re- ceived anesthesia, but not an incision. Yon Frey test results showed that, compared with the sham surgery group, incision surgery decreased the withdrawal threshold of rats at 0.5, 3, 6 and 24 hours after incision. Immunofluorescence staining in the dorsal root ganglia of the spinal cord （L3-5） showed that interleukin-10 and brain-derived neurotrophic factor were expressed mainly on small- and medium-sized neurons （diameter 〈 20 pm and 20-40 pm） and satellite cells in the dorsal root ganglia of the spinal cord （L3-5） in the sham surgery group. By contrast, in the surgery group, high expression of interleukin-10 and brain-derived neurotrophic factor appeared in large-sized neurons （diameter 〉 40 pm） at 6 and 24 hours after incision surgery, which corresponded to the decreased mechanical withdrawal threshold of rats in the surgery group. These experimental findings suggest that expression pattern shift of interleukin-10 and brain-derived neurotrophic factor induced by inci- sion surgery in dorsal root ganglia of rats was closely involved in lowering the threshold to me- chanical stimulus in the hind paw following incision surgery. Pain-related mediators induced by in- cision surgery in dorsal root ganglia of rats possibly underlie mechanical nociception in ipsilateral hind paws.
基金Supported by:the Scientific Research Program of Xiamen Science and Technology Bureau,No. 3502Z20077074
文摘BACKGROUND： Inflammatory responses in injured nerves have been recognized as important factors for initially sensitizing nociceptive neurons. Cyclooxygenase （COX） is the rate-limiting enzyme in prostaglandin synthesis, and COX-2 inhibitor is involved in mechanisms of analgesia and anti-inflammation. OBJECTIVE： To investigate the effects of COX-2 inhibitor on thermal and mechanical hyperalgesia, as well as expression of growth associated protein 43 （GAP-43） and nerve growth factor （NGF） in dorsal root ganglion, in a rat model of neuropathic pain due to chronic constriction injury. DESIGN, TIME AND SETTING： A randomized, controlled, comparison study that was performed at the Surgical Department and Pathological Laboratory, Second Affiliated Hospital of Shantou University Medical College from September 2006 to September 2007. MATERIALS： COX-2 inhibitor, Iornoxicam, was purchased from Nycomed Pharmaceutical （Austria）; rabbit anti-GAP-43, and rabbit anti-NGF polyclonal antibodies were purchased from Boster, Wuhan, China. METHODS： A total of 50 adult, Wistar rats were randomly assigned to four groups： normal control （n = 5）, model （n = 15）, normal saline control （n = 15）, and Iornoxicam treatment （n =15）. With exception of the control group, the sciatic nerve of all rats was loosely ligated to establish a model of chronic constriction injury. The model rats were divided into three subgroups according to varying post-operative survival periods： 3, 7 and 14 days （n = 5）, respectively. Rats in the Iornoxicam treatment group were intraperitoneally injected with 1.3 mg/kg lornoxicam every 12 hours throughout the entire experimental procedure. Rats in the normal saline control group were intraperitoneally injected with 1.3 mL/kg saline. MAIN OUTCOME MEASURES： Immunohistochemistry revealed expression of GAP-43 and NGF in the L5 dorsal root ganglions. Mechanical withdrawal threshold and thermal withdrawal latency were used to observe neurological behavioral changes in rats. RESULTS： The relative gray values of GAP-43- and NGF-positive neurons in the model group were remarkably increased compared with the normal control rats （P 〈 0.01）, while the relative gray values in the Iomoxicam treatment group were significantly less than the model and normal saline control groups （P 〈 0.01）. Mechanical withdrawal threshold and thermal withdrawal latency gradually decreased with increasing injury time in the model, normal saline control, and Iornoxicam treatment groups, and were significantly less than the normal control group （P 〈 0.05）. In addition, mechanical withdrawal threshold and thermal withdrawal latency were significantly greater in the Iornoxicam treatment group compared with the model and normal saline control groups （P 〈 0.05）. CONCLUSION： Intraperitoneal injection of the COX-2 inhibitor Iornoxicam attenuated mechanical and thermal hyperalgesia induced by sciatic nerve chronic constriction injury and inhibited the increased expression of GAP-43 and NGF.
