The Experts below are selected from a list of 1260 Experts worldwide ranked by ideXlab platform
Rui-xin Zhang - One of the best experts on this subject based on the ideXlab platform.
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rostral ventromedial medulla μ but not κ opioid receptors are involved in electroacupuncture anti hyperalgesia in an inflammatory pain rat model
Brain Research, 2011Co-Authors: Yu Zhang, Brian Berman, Aihui Li, Rui-xin ZhangAbstract:Abstract It has been reported that intracerebroventricular injection of a μ receptor antagonist blocked 2 but not 100 Hz electroacupuncture (EA)-produced analgesia in an uninjured animal model. Because persistent pain changes neural response to external stimulation, we hypothesized that the mechanisms of EA anti-hyperalgesia may be different in persistent pain than in health. Hyperalgesia, decreased Paw Withdrawal Latency (PWL) to a noxious thermal stimulus, was induced by subcutaneously injecting complete Freund's adjuvant (CFA) into the hind Paws of rats. Selective antagonists against μ (CTOP: D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-ThrNH2, 6.25 nmol) and κ (Nor-BIN: nor-binaltorphimine, 10 nmol) opioid receptors were infused into the rostral ventromedial medulla (RVM) 10 min before a 30-min EA treatment at acupoint Huantiao (GB30) 1 h 30 min post-CFA. PWL was measured before and 2.5 post-CFA. Both 10 Hz and 100 Hz EA-produced anti-hyperalgesia were blocked by intra-RVM μ, but not κ, receptor antagonists. Double immunofluorescence staining demonstrated that μ receptor-containing neurons were GABAnergic and that GABAa receptor-containing neurons were serotonergic in the RVM. The results demonstrated an involvement of RVM μ, but not κ, receptors in EA-produced anti-hyperalgesia. In summary, EA may induce release of endogenous endomorphins that activate μ opioid receptors in GABAnergic neurons to suppress the release of GABA. This removes the tonic inhibition of GABA on serotonergic neurons in the RVM, and activation of these serotonergic neurons inhibits pain. EA may be used as complementary treatment for inflammatory pain.
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electroacupuncture attenuates bone cancer induced hyperalgesia and inhibits spinal preprodynorphin expression in a rat model
European Journal of Pain, 2008Co-Authors: Rui-xin Zhang, Ke Ren, Brian Berman, Bing Liu, Jian-tian Qiao, Linbo Wang, Jiajia Xin, Lixing LaoAbstract:Cancer pain impairs the quality of life of cancer patients, but opioid intervention can cause significant side effects that further decrease quality of life. Although electroacupuncture (EA) has been used to treat cancer pain, its mechanisms are largely unknown. To examine its effects and underlying mechanisms on cancer pain, we injected AT-3.1 prostate cancer cells into the tibia to induce bone cancer in the male Copenhagen rat. The resulting pain was treated with 10Hz/2mA/0.4ms pulse EA for 30min daily at the point equivalent to the human acupoint GB30 (Huantiao) between days 14 and 18 after the injection. For sham control, EA needles were inserted into GB30 without stimulation. Thermal hyperalgesia, a decrease in Paw Withdrawal Latency (PWL) to a noxious thermal stimulus, and mechanical hyperalgesia, a decrease in Paw Withdrawal pressure threshold (PWPT), was measured at baseline and 20min after the EA treatment. Preprodynorphin mRNA and dynorphin were determined by RT-PCR and immunohistochemistry, respectively. Thermal and mechanical hyperalgesia developed ipsilaterally between days 12 and 18 after cancer cell inoculation. EA significantly (P<0.05) attenuated this hyperalgesia, as shown by increased PWL and PWPT, and inhibited up-regulation of preprodynorphin mRNA and dynorphin compared to sham control. Intrathecal injection of antiserum against dynorphin A (1-17) also significantly inhibited the cancer-induced hyperalgesia. These results suggest that EA alleviates bone cancer pain at least in part by suppressing dynorphin expression, and they support the clinical use of EA in the treatment of cancer pain.
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anti hyperalgesic and anti inflammatory effects of the modified chinese herbal formula huo luo xiao ling dan hlxl in rats
The American Journal of Chinese Medicine, 2006Co-Authors: Lixing Lao, Rui-xin Zhang, Ke Ren, Arthur Yin Fan, Annan Zhou, David Y W Lee, Brian BermanAbstract:Chinese herbal medicine has been used for thousands of years in China and other Asian countries to treat a variety of inflammatory diseases. The classic Chinese herbal formula, Huo Luo Xiao Ling Dan (活络效灵丹, HLXL) is commonly used in traditional Chinese herbal medicine for the treatment of joint pain and other symptoms of arthritis. The present study is an investigation of the effects of a modified HLXL extract on persistent hyperalgesia and edema in rats with peripheral inflammation. Inflammation was induced by injecting complete Freund's adjuvant (CFA) into one hind Paw. Four dosages of the extract were compared to a vehicle control. Each was administered intragastrally (i.g.) daily for seven days beginning one day before CFA. Hyperalgesia was assessed using a Paw Withdrawal Latency (PWL) test and edema was determined by measuring Paw thickness at pre-CFA and 2 hours, 24 hours, and 5 days post-CFA. Immunohistochemistry was performed 2 hours post-CFA to determine spinal Fos protein expression. Adverse eff...
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a parametric study of electroacupuncture on persistent hyperalgesia and fos protein expression in rats
Brain Research, 2004Co-Authors: Lixing Lao, Rui-xin Zhang, Brian Berman, Grant Zhang, Xiaoya Wang, Ke RenAbstract:We previously reported the anti-hyperalgesia of electroacupuncture (EA) on persistent inflammatory pain in an unrestrained, unsedated, and conscious rat model. Using this model, induced by injecting complete Freund's adjuvant (CFA) into one hind Paw, we systematically evaluated the anti-hyperalgesia of EA stimulation parameters (frequency, intensity, treatment duration, and pulse width). We assessed hyperalgesia by Paw Withdrawal Latency (PWL) to a noxious thermal stimulus and found that 10- and 100-Hz EA frequencies at a current intensity of 3 mA produced the greatest anti-hyperalgesia, when compared to other parameters. Both frequencies significantly increased PWL in the early phases of hyperalgesia (2.5 and 24 h; p < 0.05), and 10 Hz EA also significantly increased PWL in later phases (5 to 7 days; p < 0.05). A sufficient but tolerable intensity of 3 mA was more effective than lower intensities (1-2 mA). A 20-min treatment produced better anti-hyperalgesia than longer and shorter (10 and 30 min) treatments. Acupoint specificity study demonstrated that GB30 produced significant EA anti-hyperalgesia, while Waiguan (TE5) and sham points, an abdominal point and a point at the opposite aspect of GB30, did not. The spinal Fos protein expression study demonstrated that the optimal EA selectively suppressed Fos expression in superficial laminae (I/II) and activated it in deeper laminae (III/IV) of the spinal dorsal horn. The results suggest that the EA anti-hyperalgesia is parameter-dependent and point-specific, and they provide important information for designing further clinical acupuncture research on persistent inflammatory pain.
Lixing Lao - One of the best experts on this subject based on the ideXlab platform.
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Open Access Electroacupuncture Inhibits Spinal Interleukin-17A to Alleviate Inflammatory Pain in a Rat Model
2016Co-Authors: Xianze Meng, Ke Ren, Lixing Lao, Xue-yong Shen, Brian M. Berman, Pin-kang WeiAbstract:Abstract: Although acupuncture analgesia has been reported in clinical trials, its mechanisms have been unclear. It was recently reported that spinal astrocytes-produced interleukin-17A (IL-17A) facilitates inflammatory pain. Hypothesizing that electroacupuncture (EA) would suppress inflammation-enhanced IL-17A synthesis to inhibit pain, we induced hyperalgesia, as measured by decreased Paw Withdrawal Latency (PWL) to a noxious thermal stimulus, by subcutaneously injecting complete Freund’s adjuvant (CFA, 0.08 ml, 40 µg Mycobacterium tuberculosis) into the hind Paws of rats, or intrathecal (i.t.) IL-17A (400 ng in 10 µl) into the lumbar spinal cord. We then gave EA at acupoint GB30 for two 20-min periods, once immediately after CFA or IL-17A administration and again 2 h post-injection. For sham control, EA needles were inserted into GB30 without stimulation. PWL was measured before and 2.5 and 24 h after injection. Spinal IL-17A, IL-17 receptor A (IL-17RA), and phosphorylated NR1, an essential subunit of the N-methyl D-aspartate receptor (NMDAR), were determined 24 h post-CFA or –IL-17A using immunohistochemistry and western blot. Compared to sham control, EA inhibited CFA-caused thermal hyperalgesia 2.5 and 24 h post-CFA and concurrently suppressed inflammation-enhanced IL-17A and IL-17RA synthesis and NR1 phosphorylation in the ipsilateral spinal cord. EA inhibited IL-17A-produced thermal hyperalgesia, IL-17RA synthesis and NR1 phosphorylation. Our data suggest that EA inhibits inflammatory pain by blocking spinal IL-17A synthesis. Since previous study shows that IL-17A is located i
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electroacupuncture attenuates bone cancer induced hyperalgesia and inhibits spinal preprodynorphin expression in a rat model
European Journal of Pain, 2008Co-Authors: Rui-xin Zhang, Ke Ren, Brian Berman, Bing Liu, Jian-tian Qiao, Linbo Wang, Jiajia Xin, Lixing LaoAbstract:Cancer pain impairs the quality of life of cancer patients, but opioid intervention can cause significant side effects that further decrease quality of life. Although electroacupuncture (EA) has been used to treat cancer pain, its mechanisms are largely unknown. To examine its effects and underlying mechanisms on cancer pain, we injected AT-3.1 prostate cancer cells into the tibia to induce bone cancer in the male Copenhagen rat. The resulting pain was treated with 10Hz/2mA/0.4ms pulse EA for 30min daily at the point equivalent to the human acupoint GB30 (Huantiao) between days 14 and 18 after the injection. For sham control, EA needles were inserted into GB30 without stimulation. Thermal hyperalgesia, a decrease in Paw Withdrawal Latency (PWL) to a noxious thermal stimulus, and mechanical hyperalgesia, a decrease in Paw Withdrawal pressure threshold (PWPT), was measured at baseline and 20min after the EA treatment. Preprodynorphin mRNA and dynorphin were determined by RT-PCR and immunohistochemistry, respectively. Thermal and mechanical hyperalgesia developed ipsilaterally between days 12 and 18 after cancer cell inoculation. EA significantly (P<0.05) attenuated this hyperalgesia, as shown by increased PWL and PWPT, and inhibited up-regulation of preprodynorphin mRNA and dynorphin compared to sham control. Intrathecal injection of antiserum against dynorphin A (1-17) also significantly inhibited the cancer-induced hyperalgesia. These results suggest that EA alleviates bone cancer pain at least in part by suppressing dynorphin expression, and they support the clinical use of EA in the treatment of cancer pain.
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anti hyperalgesic and anti inflammatory effects of the modified chinese herbal formula huo luo xiao ling dan hlxl in rats
The American Journal of Chinese Medicine, 2006Co-Authors: Lixing Lao, Rui-xin Zhang, Ke Ren, Arthur Yin Fan, Annan Zhou, David Y W Lee, Brian BermanAbstract:Chinese herbal medicine has been used for thousands of years in China and other Asian countries to treat a variety of inflammatory diseases. The classic Chinese herbal formula, Huo Luo Xiao Ling Dan (活络效灵丹, HLXL) is commonly used in traditional Chinese herbal medicine for the treatment of joint pain and other symptoms of arthritis. The present study is an investigation of the effects of a modified HLXL extract on persistent hyperalgesia and edema in rats with peripheral inflammation. Inflammation was induced by injecting complete Freund's adjuvant (CFA) into one hind Paw. Four dosages of the extract were compared to a vehicle control. Each was administered intragastrally (i.g.) daily for seven days beginning one day before CFA. Hyperalgesia was assessed using a Paw Withdrawal Latency (PWL) test and edema was determined by measuring Paw thickness at pre-CFA and 2 hours, 24 hours, and 5 days post-CFA. Immunohistochemistry was performed 2 hours post-CFA to determine spinal Fos protein expression. Adverse eff...
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a parametric study of electroacupuncture on persistent hyperalgesia and fos protein expression in rats
Brain Research, 2004Co-Authors: Lixing Lao, Rui-xin Zhang, Brian Berman, Grant Zhang, Xiaoya Wang, Ke RenAbstract:We previously reported the anti-hyperalgesia of electroacupuncture (EA) on persistent inflammatory pain in an unrestrained, unsedated, and conscious rat model. Using this model, induced by injecting complete Freund's adjuvant (CFA) into one hind Paw, we systematically evaluated the anti-hyperalgesia of EA stimulation parameters (frequency, intensity, treatment duration, and pulse width). We assessed hyperalgesia by Paw Withdrawal Latency (PWL) to a noxious thermal stimulus and found that 10- and 100-Hz EA frequencies at a current intensity of 3 mA produced the greatest anti-hyperalgesia, when compared to other parameters. Both frequencies significantly increased PWL in the early phases of hyperalgesia (2.5 and 24 h; p < 0.05), and 10 Hz EA also significantly increased PWL in later phases (5 to 7 days; p < 0.05). A sufficient but tolerable intensity of 3 mA was more effective than lower intensities (1-2 mA). A 20-min treatment produced better anti-hyperalgesia than longer and shorter (10 and 30 min) treatments. Acupoint specificity study demonstrated that GB30 produced significant EA anti-hyperalgesia, while Waiguan (TE5) and sham points, an abdominal point and a point at the opposite aspect of GB30, did not. The spinal Fos protein expression study demonstrated that the optimal EA selectively suppressed Fos expression in superficial laminae (I/II) and activated it in deeper laminae (III/IV) of the spinal dorsal horn. The results suggest that the EA anti-hyperalgesia is parameter-dependent and point-specific, and they provide important information for designing further clinical acupuncture research on persistent inflammatory pain.
Brian Berman - One of the best experts on this subject based on the ideXlab platform.
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rostral ventromedial medulla μ but not κ opioid receptors are involved in electroacupuncture anti hyperalgesia in an inflammatory pain rat model
Brain Research, 2011Co-Authors: Yu Zhang, Brian Berman, Aihui Li, Rui-xin ZhangAbstract:Abstract It has been reported that intracerebroventricular injection of a μ receptor antagonist blocked 2 but not 100 Hz electroacupuncture (EA)-produced analgesia in an uninjured animal model. Because persistent pain changes neural response to external stimulation, we hypothesized that the mechanisms of EA anti-hyperalgesia may be different in persistent pain than in health. Hyperalgesia, decreased Paw Withdrawal Latency (PWL) to a noxious thermal stimulus, was induced by subcutaneously injecting complete Freund's adjuvant (CFA) into the hind Paws of rats. Selective antagonists against μ (CTOP: D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-ThrNH2, 6.25 nmol) and κ (Nor-BIN: nor-binaltorphimine, 10 nmol) opioid receptors were infused into the rostral ventromedial medulla (RVM) 10 min before a 30-min EA treatment at acupoint Huantiao (GB30) 1 h 30 min post-CFA. PWL was measured before and 2.5 post-CFA. Both 10 Hz and 100 Hz EA-produced anti-hyperalgesia were blocked by intra-RVM μ, but not κ, receptor antagonists. Double immunofluorescence staining demonstrated that μ receptor-containing neurons were GABAnergic and that GABAa receptor-containing neurons were serotonergic in the RVM. The results demonstrated an involvement of RVM μ, but not κ, receptors in EA-produced anti-hyperalgesia. In summary, EA may induce release of endogenous endomorphins that activate μ opioid receptors in GABAnergic neurons to suppress the release of GABA. This removes the tonic inhibition of GABA on serotonergic neurons in the RVM, and activation of these serotonergic neurons inhibits pain. EA may be used as complementary treatment for inflammatory pain.
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electroacupuncture attenuates bone cancer induced hyperalgesia and inhibits spinal preprodynorphin expression in a rat model
European Journal of Pain, 2008Co-Authors: Rui-xin Zhang, Ke Ren, Brian Berman, Bing Liu, Jian-tian Qiao, Linbo Wang, Jiajia Xin, Lixing LaoAbstract:Cancer pain impairs the quality of life of cancer patients, but opioid intervention can cause significant side effects that further decrease quality of life. Although electroacupuncture (EA) has been used to treat cancer pain, its mechanisms are largely unknown. To examine its effects and underlying mechanisms on cancer pain, we injected AT-3.1 prostate cancer cells into the tibia to induce bone cancer in the male Copenhagen rat. The resulting pain was treated with 10Hz/2mA/0.4ms pulse EA for 30min daily at the point equivalent to the human acupoint GB30 (Huantiao) between days 14 and 18 after the injection. For sham control, EA needles were inserted into GB30 without stimulation. Thermal hyperalgesia, a decrease in Paw Withdrawal Latency (PWL) to a noxious thermal stimulus, and mechanical hyperalgesia, a decrease in Paw Withdrawal pressure threshold (PWPT), was measured at baseline and 20min after the EA treatment. Preprodynorphin mRNA and dynorphin were determined by RT-PCR and immunohistochemistry, respectively. Thermal and mechanical hyperalgesia developed ipsilaterally between days 12 and 18 after cancer cell inoculation. EA significantly (P<0.05) attenuated this hyperalgesia, as shown by increased PWL and PWPT, and inhibited up-regulation of preprodynorphin mRNA and dynorphin compared to sham control. Intrathecal injection of antiserum against dynorphin A (1-17) also significantly inhibited the cancer-induced hyperalgesia. These results suggest that EA alleviates bone cancer pain at least in part by suppressing dynorphin expression, and they support the clinical use of EA in the treatment of cancer pain.
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anti hyperalgesic and anti inflammatory effects of the modified chinese herbal formula huo luo xiao ling dan hlxl in rats
The American Journal of Chinese Medicine, 2006Co-Authors: Lixing Lao, Rui-xin Zhang, Ke Ren, Arthur Yin Fan, Annan Zhou, David Y W Lee, Brian BermanAbstract:Chinese herbal medicine has been used for thousands of years in China and other Asian countries to treat a variety of inflammatory diseases. The classic Chinese herbal formula, Huo Luo Xiao Ling Dan (活络效灵丹, HLXL) is commonly used in traditional Chinese herbal medicine for the treatment of joint pain and other symptoms of arthritis. The present study is an investigation of the effects of a modified HLXL extract on persistent hyperalgesia and edema in rats with peripheral inflammation. Inflammation was induced by injecting complete Freund's adjuvant (CFA) into one hind Paw. Four dosages of the extract were compared to a vehicle control. Each was administered intragastrally (i.g.) daily for seven days beginning one day before CFA. Hyperalgesia was assessed using a Paw Withdrawal Latency (PWL) test and edema was determined by measuring Paw thickness at pre-CFA and 2 hours, 24 hours, and 5 days post-CFA. Immunohistochemistry was performed 2 hours post-CFA to determine spinal Fos protein expression. Adverse eff...
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a parametric study of electroacupuncture on persistent hyperalgesia and fos protein expression in rats
Brain Research, 2004Co-Authors: Lixing Lao, Rui-xin Zhang, Brian Berman, Grant Zhang, Xiaoya Wang, Ke RenAbstract:We previously reported the anti-hyperalgesia of electroacupuncture (EA) on persistent inflammatory pain in an unrestrained, unsedated, and conscious rat model. Using this model, induced by injecting complete Freund's adjuvant (CFA) into one hind Paw, we systematically evaluated the anti-hyperalgesia of EA stimulation parameters (frequency, intensity, treatment duration, and pulse width). We assessed hyperalgesia by Paw Withdrawal Latency (PWL) to a noxious thermal stimulus and found that 10- and 100-Hz EA frequencies at a current intensity of 3 mA produced the greatest anti-hyperalgesia, when compared to other parameters. Both frequencies significantly increased PWL in the early phases of hyperalgesia (2.5 and 24 h; p < 0.05), and 10 Hz EA also significantly increased PWL in later phases (5 to 7 days; p < 0.05). A sufficient but tolerable intensity of 3 mA was more effective than lower intensities (1-2 mA). A 20-min treatment produced better anti-hyperalgesia than longer and shorter (10 and 30 min) treatments. Acupoint specificity study demonstrated that GB30 produced significant EA anti-hyperalgesia, while Waiguan (TE5) and sham points, an abdominal point and a point at the opposite aspect of GB30, did not. The spinal Fos protein expression study demonstrated that the optimal EA selectively suppressed Fos expression in superficial laminae (I/II) and activated it in deeper laminae (III/IV) of the spinal dorsal horn. The results suggest that the EA anti-hyperalgesia is parameter-dependent and point-specific, and they provide important information for designing further clinical acupuncture research on persistent inflammatory pain.
Tony L Yaksh - One of the best experts on this subject based on the ideXlab platform.
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characterization of muscarinic receptor subtypes that mediate antinociception in the rat spinal cord
Anesthesia & Analgesia, 1997Co-Authors: Mohamed Naguib, Tony L YakshAbstract:Spinal cholinergic receptors are involved in mediating antinociceptive effects.To characterize the receptor subtypes modulating nociceptive transmission, we first determined the antinociceptive effects of intrathecally administered muscarinic agonists (McN-A-343 and carbachol) and a cholinesterase inhibitor (neostigmine) in rats. The antagonist potencies of muscarinic antagonists with different preferences for muscarinic receptors [atropine, pirenzepine (M1), methoctramine (M2), and 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP; M3)] were then examined for McN-A-343, carbachol, and neostigmine. After determining the time of peak effect for each antagonist, the just maximally effective (JME) dose of each agonist was given in conjunction with one of the several doses of the antagonists. The three agents produced a dose-dependent increase in Paw Withdrawal Latency, with the following 50% effective dose and the following JME doses: neostigmine 6 and 14 nmol, carbachol 29 and 110 nmol, and McN-A-343 354 and 630 nmol. The rank of order of potency (and median infective dose in nanomoles) for the antagonists was: neostigmine = (atropine 14 > 4-DAMP 44 >> methoctramine >137, and pirenzepine >236); carbachol = (pirenzepine 0.5 = atropine 0.6 > 4-DAMP 5 >> methoctramine >137); McN-A-343 = (pirenzepine 0.5 > atropine 3 > 4-DAMP 6 >> methoctramine >137). Our results suggest that the M1 and possibly the M3 muscarinic receptors mediate spinal antinociception in the rat. Implications: Spinal muscarinic agonists, such as carbachol and the cholinesterase inhibitor neostigmine, induce a potent analgesia in the rat. Using selective receptor antagonists, we have shown that these effects are likely mediated by spinal M1 and/or M3 receptor subtypes. (Anesth Analg 1997;85:847-53)
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spinal pharmacology of thermal hyperesthesia induced by constriction injury of sciatic nerve excitatory amino acid antagonists
Pain, 1992Co-Authors: Tatsuo Yamamoto, Tony L YakshAbstract:Abstract This study evaluated the effects of spinally administered excitatory amino acid antagonists on the thermal hyperesthetic state induced by unilateral partial ligation of the sciatic nerve in the rat. The measured response was the Latency to Paw Withdrawal of each hind Paw after application of a focused heat lamp on the plantar surface of the Paw through a glass plate upon which the animal stood. In this work, antagonists (MK801, dl -2-amino-5-phosphonovalerate, ketamine) of the N- methyl- d -aspartate receptor (NMDA), the glycine potentiation site at the NMDA receptor (5-chloro-indole-2-carboxylic acid) and non-NMDA receptor (kynurenic acid: g- d -glutamylaminomethyl sulphonate) were injected through chronically implanted lumbar intrathecal catheters in normal rats (no lesions) and in rats with unilateral constriction injury. In the normal rat study, NMDA and non-NMDA antagonists had little effect upon Paw Withdrawal Latency at intrathecal doses which did not produce readily detectable motor weakness. In the hyperesthetic rat study, NMDA antagonists would temporarily eliminate the hyperesthetic state at doses below those which altered the response Latency of the normal Paw or which altered motor function. These results suggested that spinal NMDA receptors play an important role in the hyperesthetic state induced by peripheral nerve injury.
Ke Ren - One of the best experts on this subject based on the ideXlab platform.
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Open Access Electroacupuncture Inhibits Spinal Interleukin-17A to Alleviate Inflammatory Pain in a Rat Model
2016Co-Authors: Xianze Meng, Ke Ren, Lixing Lao, Xue-yong Shen, Brian M. Berman, Pin-kang WeiAbstract:Abstract: Although acupuncture analgesia has been reported in clinical trials, its mechanisms have been unclear. It was recently reported that spinal astrocytes-produced interleukin-17A (IL-17A) facilitates inflammatory pain. Hypothesizing that electroacupuncture (EA) would suppress inflammation-enhanced IL-17A synthesis to inhibit pain, we induced hyperalgesia, as measured by decreased Paw Withdrawal Latency (PWL) to a noxious thermal stimulus, by subcutaneously injecting complete Freund’s adjuvant (CFA, 0.08 ml, 40 µg Mycobacterium tuberculosis) into the hind Paws of rats, or intrathecal (i.t.) IL-17A (400 ng in 10 µl) into the lumbar spinal cord. We then gave EA at acupoint GB30 for two 20-min periods, once immediately after CFA or IL-17A administration and again 2 h post-injection. For sham control, EA needles were inserted into GB30 without stimulation. PWL was measured before and 2.5 and 24 h after injection. Spinal IL-17A, IL-17 receptor A (IL-17RA), and phosphorylated NR1, an essential subunit of the N-methyl D-aspartate receptor (NMDAR), were determined 24 h post-CFA or –IL-17A using immunohistochemistry and western blot. Compared to sham control, EA inhibited CFA-caused thermal hyperalgesia 2.5 and 24 h post-CFA and concurrently suppressed inflammation-enhanced IL-17A and IL-17RA synthesis and NR1 phosphorylation in the ipsilateral spinal cord. EA inhibited IL-17A-produced thermal hyperalgesia, IL-17RA synthesis and NR1 phosphorylation. Our data suggest that EA inhibits inflammatory pain by blocking spinal IL-17A synthesis. Since previous study shows that IL-17A is located i
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electroacupuncture attenuates bone cancer induced hyperalgesia and inhibits spinal preprodynorphin expression in a rat model
European Journal of Pain, 2008Co-Authors: Rui-xin Zhang, Ke Ren, Brian Berman, Bing Liu, Jian-tian Qiao, Linbo Wang, Jiajia Xin, Lixing LaoAbstract:Cancer pain impairs the quality of life of cancer patients, but opioid intervention can cause significant side effects that further decrease quality of life. Although electroacupuncture (EA) has been used to treat cancer pain, its mechanisms are largely unknown. To examine its effects and underlying mechanisms on cancer pain, we injected AT-3.1 prostate cancer cells into the tibia to induce bone cancer in the male Copenhagen rat. The resulting pain was treated with 10Hz/2mA/0.4ms pulse EA for 30min daily at the point equivalent to the human acupoint GB30 (Huantiao) between days 14 and 18 after the injection. For sham control, EA needles were inserted into GB30 without stimulation. Thermal hyperalgesia, a decrease in Paw Withdrawal Latency (PWL) to a noxious thermal stimulus, and mechanical hyperalgesia, a decrease in Paw Withdrawal pressure threshold (PWPT), was measured at baseline and 20min after the EA treatment. Preprodynorphin mRNA and dynorphin were determined by RT-PCR and immunohistochemistry, respectively. Thermal and mechanical hyperalgesia developed ipsilaterally between days 12 and 18 after cancer cell inoculation. EA significantly (P<0.05) attenuated this hyperalgesia, as shown by increased PWL and PWPT, and inhibited up-regulation of preprodynorphin mRNA and dynorphin compared to sham control. Intrathecal injection of antiserum against dynorphin A (1-17) also significantly inhibited the cancer-induced hyperalgesia. These results suggest that EA alleviates bone cancer pain at least in part by suppressing dynorphin expression, and they support the clinical use of EA in the treatment of cancer pain.
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anti hyperalgesic and anti inflammatory effects of the modified chinese herbal formula huo luo xiao ling dan hlxl in rats
The American Journal of Chinese Medicine, 2006Co-Authors: Lixing Lao, Rui-xin Zhang, Ke Ren, Arthur Yin Fan, Annan Zhou, David Y W Lee, Brian BermanAbstract:Chinese herbal medicine has been used for thousands of years in China and other Asian countries to treat a variety of inflammatory diseases. The classic Chinese herbal formula, Huo Luo Xiao Ling Dan (活络效灵丹, HLXL) is commonly used in traditional Chinese herbal medicine for the treatment of joint pain and other symptoms of arthritis. The present study is an investigation of the effects of a modified HLXL extract on persistent hyperalgesia and edema in rats with peripheral inflammation. Inflammation was induced by injecting complete Freund's adjuvant (CFA) into one hind Paw. Four dosages of the extract were compared to a vehicle control. Each was administered intragastrally (i.g.) daily for seven days beginning one day before CFA. Hyperalgesia was assessed using a Paw Withdrawal Latency (PWL) test and edema was determined by measuring Paw thickness at pre-CFA and 2 hours, 24 hours, and 5 days post-CFA. Immunohistochemistry was performed 2 hours post-CFA to determine spinal Fos protein expression. Adverse eff...
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a parametric study of electroacupuncture on persistent hyperalgesia and fos protein expression in rats
Brain Research, 2004Co-Authors: Lixing Lao, Rui-xin Zhang, Brian Berman, Grant Zhang, Xiaoya Wang, Ke RenAbstract:We previously reported the anti-hyperalgesia of electroacupuncture (EA) on persistent inflammatory pain in an unrestrained, unsedated, and conscious rat model. Using this model, induced by injecting complete Freund's adjuvant (CFA) into one hind Paw, we systematically evaluated the anti-hyperalgesia of EA stimulation parameters (frequency, intensity, treatment duration, and pulse width). We assessed hyperalgesia by Paw Withdrawal Latency (PWL) to a noxious thermal stimulus and found that 10- and 100-Hz EA frequencies at a current intensity of 3 mA produced the greatest anti-hyperalgesia, when compared to other parameters. Both frequencies significantly increased PWL in the early phases of hyperalgesia (2.5 and 24 h; p < 0.05), and 10 Hz EA also significantly increased PWL in later phases (5 to 7 days; p < 0.05). A sufficient but tolerable intensity of 3 mA was more effective than lower intensities (1-2 mA). A 20-min treatment produced better anti-hyperalgesia than longer and shorter (10 and 30 min) treatments. Acupoint specificity study demonstrated that GB30 produced significant EA anti-hyperalgesia, while Waiguan (TE5) and sham points, an abdominal point and a point at the opposite aspect of GB30, did not. The spinal Fos protein expression study demonstrated that the optimal EA selectively suppressed Fos expression in superficial laminae (I/II) and activated it in deeper laminae (III/IV) of the spinal dorsal horn. The results suggest that the EA anti-hyperalgesia is parameter-dependent and point-specific, and they provide important information for designing further clinical acupuncture research on persistent inflammatory pain.