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Hiroshi Ueda - One of the best experts on this subject based on the ideXlab platform.
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increased expression of vanilloid receptor 1 on myelinated primary afferent neurons contributes to the antihyperalgesic effect of Capsaicin cream in diabetic neuropathic pain in mice
Journal of Pharmacology and Experimental Therapeutics, 2003Co-Authors: Harunor M Rashid, Makoto Inoue, Shiho Bakoshi, Hiroshi UedaAbstract:Topical Capsaicin is believed to alleviate pain by desensitizing the vanilloid receptor 1 (VR1) at the peripheral nerve endings. Here, we report that an up-regulation of VR1 expression on myelinated fibers contributes to the antihyperalgesic effect of Capsaicin cream in streptozotocin (STZ)-induced diabetic neuropathic pain. Intravenous injection of STZ (200 mg/kg) in mice caused rapid onset of diabetes within 24 h. Thermal and mechanical hyperalgesia developed by 3 days after STZ injection and persisted at all time points tested until 28 days. There was also hyperalgesic response to intraplantar (i.pl.) prostaglandin I2 (PGI2) agonist-induced nociception in such mice. Application of Capsaicin cream dose dependently reversed the thermal, mechanical, and PGI2 agonist-induced hyperalgesia observed in the diabetic mice. The i.pl. injection of Capsaicin solution (0.4 μg/20 μl) produced nociceptive biting-licking responses in control mice, and these responses were significantly increased in STZ-induced diabetic mice. After neonatal Capsaicin-treatment, which destroys most unmyelinated C-fibers, the i.pl. Capsaicin-induced biting-licking responses were almost abolished. However, in neonatal Capsaicin-treated diabetic mice, the i.pl. Capsaicin-induced biting-licking responses reappeared. The i.pl. Capsaicin-induced biting-licking responses were blocked by the competitive VR1 antagonist capsazepine. All these results suggest an increase in Capsaicin receptor on myelinated fibers due to diabetes. Finally, we confirmed the up-regulation of VR1 expression on myelinated primary afferent neurons of diabetic mice by immunohistochemistry. Together, our results suggest that increased expression of VR1 on myelinated fibers might contribute to the antihyperalgesic effect of topical Capsaicin in diabetic neuropathic pain.
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Novel Expression of Vanilloid Receptor 1 on Capsaicin-Insensitive Fibers Accounts for the Analgesic Effect of Capsaicin Cream in Neuropathic Pain
The Journal of pharmacology and experimental therapeutics, 2002Co-Authors: Harunor Rashid, Makoto Inoue, Saori Kondo, Toshiko Kawashima, Shiho Bakoshi, Hiroshi UedaAbstract:Here, we investigated the mechanism of the antihyperalgesic effect of Capsaicin cream in the nerve injury-induced neuropathic pain model in mice. In naive mice, application of Capsaicin cream onto footpad caused no significant changes in the thermal latency in contrast to the severe thermal hyperalgesia induced by a Capsaicin ointment. On the other hand, application of the cream 3 h before test concentration dependently reversed both thermal and mechanical hyperalgesia observed after partial sciatic nerve injury in mice. In algogenic-induced nociceptive flexion (ANF) test, application of 0.1% Capsaicin cream in naive mice blocked intraplantar (i.pl.) nociceptin- and ATP-induced flexion responses, whereas prostaglandin I2(PGI2) agonist-induced responses were unaffected. After nerve injury PGI2 agonist-induced flexion responses were hypersensitized, and Capsaicin cream concentration dependently blocked these hyperalgesic responses. Intraplantar injection of Capsaicin solution in ANF test also produced potent flexion responses in naive mice that were lost after neonatal Capsaicin-treatment. Partial sciatic nerve injury in neonatal Capsaicin-treated mice caused reappearance of i.pl. Capsaicin-induced flexion responses, suggesting novel expression of Capsaicin receptors due to injury. The PGI2agonist-induced responses were also hypersensitized in such injured mice. Capsaicin cream completely reversed both i.pl. Capsaicin- or i.pl. PGI2 agonist-induced hyperalgesia in neonatal Capsaicin-treated injured mice. Finally, novel expression of VR1 receptors on neonatal Capsaicin-insensitive neurons after nerve injury was confirmed by immunohistochemistry. The newly expressed VR1 receptors after nerve injury were mainly confined to A-fibers. Together, our results suggest that novel expression of Capsaicin receptors in neuropathic condition contributes to the analgesic effects of the Capsaicin cream.
Carlo Alberto Maggi - One of the best experts on this subject based on the ideXlab platform.
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Effect of capsazepine on the release of calcitonin gene‐related peptide‐like immunoreactivity (CGRP‐LI) induced by low pH, Capsaicin and potassium in rat soleus muscle
British Journal of Pharmacology, 1993Co-Authors: Paolo Santicioli, Stuart Bevan, Elena Del Bianco, Michela Figini, Carlo Alberto MaggiAbstract:1. We have determined the effect of the competitive antagonist capsazepine at the Capsaicin receptor on the release of calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) from rat isolated soleus muscle induced by Capsaicin (1 microM), by superfusion with low pH medium (pH 5) or by KCl (80 mM). 2. Each one of the three stimuli tested produced a marked CGRP-LI release. Total evoked release (fmol g-1) was 482 +/- 69, 169 +/- 20 and 253 +/- 43 for capsiacin, low pH medium and KCL, respectively. 3. Prior application of capsiacin (10 microM for 30 min followed by 30 min of washout) to produce capasaicin desensitization in vitro abolished CGRP-LI release induced by the three stimuli. 4. Capsazepine (1-100 microM, 45 min preincubation) inhibited the evoked CGRP-LI release. Capsaicin-induced release was significantly inhibited by 77, 92 and 96% with 10, 30 and 100 microM capsazepine, respectively. Low pH-induced release was inhibited by 78, 84, 88 and 93% with 3, 10, 30 and 100 microM capsazepine, respectively. KCl-induced release was significantly inhibited by 55 and 93% with 30 and 100 microM (but not with 10 microM) capsazepine, respectively. 5. These findings demonstrate that capsazepine prevents low pH- and Capsaicin-induced CGRP-LI release from rat soleus muscle at concentrations which do not affect the release evoked by KCl. These findings imply a relationship between the action of low pH and activation of the Capsaicin receptor. At high concentrations, capsazepine produces a nonspecific inhibitory effect on CGRP-LI release from peripheral endings of the Capsaicin-sensitive primary afferent neurone.
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effect of capsazepine on the release of calcitonin gene related peptide like immunoreactivity cgrp li induced by low ph Capsaicin and potassium in rat soleus muscle
British Journal of Pharmacology, 1993Co-Authors: Paolo Santicioli, Stuart Bevan, Elena Del Bianco, Michela Figini, Carlo Alberto MaggiAbstract:1. We have determined the effect of the competitive antagonist capsazepine at the Capsaicin receptor on the release of calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) from rat isolated soleus muscle induced by Capsaicin (1 microM), by superfusion with low pH medium (pH 5) or by KCl (80 mM). 2. Each one of the three stimuli tested produced a marked CGRP-LI release. Total evoked release (fmol g-1) was 482 +/- 69, 169 +/- 20 and 253 +/- 43 for capsiacin, low pH medium and KCL, respectively. 3. Prior application of capsiacin (10 microM for 30 min followed by 30 min of washout) to produce capasaicin desensitization in vitro abolished CGRP-LI release induced by the three stimuli. 4. Capsazepine (1-100 microM, 45 min preincubation) inhibited the evoked CGRP-LI release. Capsaicin-induced release was significantly inhibited by 77, 92 and 96% with 10, 30 and 100 microM capsazepine, respectively. Low pH-induced release was inhibited by 78, 84, 88 and 93% with 3, 10, 30 and 100 microM capsazepine, respectively. KCl-induced release was significantly inhibited by 55 and 93% with 30 and 100 microM (but not with 10 microM) capsazepine, respectively. 5. These findings demonstrate that capsazepine prevents low pH- and Capsaicin-induced CGRP-LI release from rat soleus muscle at concentrations which do not affect the release evoked by KCl. These findings imply a relationship between the action of low pH and activation of the Capsaicin receptor. At high concentrations, capsazepine produces a nonspecific inhibitory effect on CGRP-LI release from peripheral endings of the Capsaicin-sensitive primary afferent neurone.
Shiho Bakoshi - One of the best experts on this subject based on the ideXlab platform.
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increased expression of vanilloid receptor 1 on myelinated primary afferent neurons contributes to the antihyperalgesic effect of Capsaicin cream in diabetic neuropathic pain in mice
Journal of Pharmacology and Experimental Therapeutics, 2003Co-Authors: Harunor M Rashid, Makoto Inoue, Shiho Bakoshi, Hiroshi UedaAbstract:Topical Capsaicin is believed to alleviate pain by desensitizing the vanilloid receptor 1 (VR1) at the peripheral nerve endings. Here, we report that an up-regulation of VR1 expression on myelinated fibers contributes to the antihyperalgesic effect of Capsaicin cream in streptozotocin (STZ)-induced diabetic neuropathic pain. Intravenous injection of STZ (200 mg/kg) in mice caused rapid onset of diabetes within 24 h. Thermal and mechanical hyperalgesia developed by 3 days after STZ injection and persisted at all time points tested until 28 days. There was also hyperalgesic response to intraplantar (i.pl.) prostaglandin I2 (PGI2) agonist-induced nociception in such mice. Application of Capsaicin cream dose dependently reversed the thermal, mechanical, and PGI2 agonist-induced hyperalgesia observed in the diabetic mice. The i.pl. injection of Capsaicin solution (0.4 μg/20 μl) produced nociceptive biting-licking responses in control mice, and these responses were significantly increased in STZ-induced diabetic mice. After neonatal Capsaicin-treatment, which destroys most unmyelinated C-fibers, the i.pl. Capsaicin-induced biting-licking responses were almost abolished. However, in neonatal Capsaicin-treated diabetic mice, the i.pl. Capsaicin-induced biting-licking responses reappeared. The i.pl. Capsaicin-induced biting-licking responses were blocked by the competitive VR1 antagonist capsazepine. All these results suggest an increase in Capsaicin receptor on myelinated fibers due to diabetes. Finally, we confirmed the up-regulation of VR1 expression on myelinated primary afferent neurons of diabetic mice by immunohistochemistry. Together, our results suggest that increased expression of VR1 on myelinated fibers might contribute to the antihyperalgesic effect of topical Capsaicin in diabetic neuropathic pain.
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Novel Expression of Vanilloid Receptor 1 on Capsaicin-Insensitive Fibers Accounts for the Analgesic Effect of Capsaicin Cream in Neuropathic Pain
The Journal of pharmacology and experimental therapeutics, 2002Co-Authors: Harunor Rashid, Makoto Inoue, Saori Kondo, Toshiko Kawashima, Shiho Bakoshi, Hiroshi UedaAbstract:Here, we investigated the mechanism of the antihyperalgesic effect of Capsaicin cream in the nerve injury-induced neuropathic pain model in mice. In naive mice, application of Capsaicin cream onto footpad caused no significant changes in the thermal latency in contrast to the severe thermal hyperalgesia induced by a Capsaicin ointment. On the other hand, application of the cream 3 h before test concentration dependently reversed both thermal and mechanical hyperalgesia observed after partial sciatic nerve injury in mice. In algogenic-induced nociceptive flexion (ANF) test, application of 0.1% Capsaicin cream in naive mice blocked intraplantar (i.pl.) nociceptin- and ATP-induced flexion responses, whereas prostaglandin I2(PGI2) agonist-induced responses were unaffected. After nerve injury PGI2 agonist-induced flexion responses were hypersensitized, and Capsaicin cream concentration dependently blocked these hyperalgesic responses. Intraplantar injection of Capsaicin solution in ANF test also produced potent flexion responses in naive mice that were lost after neonatal Capsaicin-treatment. Partial sciatic nerve injury in neonatal Capsaicin-treated mice caused reappearance of i.pl. Capsaicin-induced flexion responses, suggesting novel expression of Capsaicin receptors due to injury. The PGI2agonist-induced responses were also hypersensitized in such injured mice. Capsaicin cream completely reversed both i.pl. Capsaicin- or i.pl. PGI2 agonist-induced hyperalgesia in neonatal Capsaicin-treated injured mice. Finally, novel expression of VR1 receptors on neonatal Capsaicin-insensitive neurons after nerve injury was confirmed by immunohistochemistry. The newly expressed VR1 receptors after nerve injury were mainly confined to A-fibers. Together, our results suggest that novel expression of Capsaicin receptors in neuropathic condition contributes to the analgesic effects of the Capsaicin cream.
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The effects of Capsaicin cream on prostaglandin-induced allodynia.
Anesthesia & Analgesia, 2001Co-Authors: Toshiaki Minami, Shiho Bakoshi, Hiroyuki Nakano, Onori Mine, Tadatoshi Muratani, Hidemaro MoriAbstract:UNLABELLED: Although intradermal injection of Capsaicin produces acute pain and secondary hyperalgesia, long-term topical application of Capsaicin cream has been used as a medication for pain relief in various pain conditions. We previously reported that intrathecal administration of prostaglandin (PG) E(2) and PGF(2alpha) into mice induced touch-evoked pain (allodynia) through Capsaicin-sensitive and Capsaicin-insensitive afferent fibers, respectively. To clarify the mechanism of an analgesic effect by Capsaicin cream, here we applied it to the tail and hind paws of mice and investigated its effects on PGE(2)- and PGF(2alpha)-induced allodynia. Twenty-four-hour pretreatment of mice with 0.025% or 0.05% Capsaicin cream markedly alleviated allodynia induced by PGE(2), but not by PGF(2alpha). These results suggest that the topical application of Capsaicin cream modulates Capsaicin-sensitive afferents and ameliorates allodynia evoked by PGE(2) at the spinal level. IMPLICATIONS: Topical application of Capsaicin cream alleviates touch-evoked pain induced by the intrathecal administration of prostaglandin E(2). This study may provide a rationale for the use of Capsaicin cream as a therapeutic drug for pain relief.
Rolf Håkanson - One of the best experts on this subject based on the ideXlab platform.
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Effects of ruthenium red and capsazepine on C-fibres in the rabbit iris.
British Journal of Pharmacology, 1993Co-Authors: Zun-yi Wang, Rolf HåkansonAbstract:1 We have investigated the effects of ruthenium red and capsazepine on a C-fibre-smooth muscle preparation (the rabbit isolated iris sphincter muscle). 2 Like Capsaicin, ruthenium red and capsazepine were found to produce contractions in a concentration-dependent manner. C-fibre activation was held to be responsible since the contractions could be inhibited by tachykinin receptor blockade. 3 Both ruthenium red and capsazepine inhibited Capsaicin-induced contractions concentration-dependently; the pIC50 values were 5.1 and 4.9, respectively. The contractions induced by bradykinin, which, like Capsaicin, acts by releasing tachykinins from C-fibres, were also inhibited by ruthenium red and capsazepine in a concentration-dependent manner; the pIC50 values were 4.1 and 4.6, respectively. 4 Electrically evoked, tachykinin-mediated contractions were inhibited by ruthenium red and capsazepine in a concentration-dependent manner; the pIC50 values were 4.3 and 4.5, respectively. 5 The contractile response to neurokinin A (NKA) was inhibited by capsazepine (and by Capsaicin), but not by ruthenium red, in a concentration-dependent manner; the pIC50 value was 4.3. 6 The results suggest that, besides their ability to antagonize Capsaicin, ruthenium red and capsazepine possess a weak Capsaicin-like effect. Conceivably, capsazepine interacts with binding sites for Capsaicin, acting as a partial agonist/antagonist, while ruthenium red interacts with Capsaicin-operated cation channels. The inhibition of electrically evoked- or bradykinin-induced responses by capsazepine and ruthenium red suggests that Capsaicin/capsazepine binding sites and Capsaicin-operated cation channels play a role in the process of transmitter release in response not only to Capsaicin but also to other C-fibre stimuli. In addition, capsazepine (and Capsaicin) may affect smooth muscle non-specifically since the response to NKA was also inhibited by this drug. The fact that ruthenium red did not affect the response to NKA provides further evidence that ruthenium red acts in a mode different from that of capsazepine.
Eran Goldin - One of the best experts on this subject based on the ideXlab platform.
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topical Capsaicin a novel and effective treatment for idiopathic intractable pruritus ani a randomised placebo controlled crossover study
Gut, 2003Co-Authors: Joseph Lysy, D Keret, Yardena Israelit, Avigail Shmueli, M Sistieryittah, N Straussliviatan, Victoria Mindrul, Eran GoldinAbstract:Purpose: Pruritus ani is a common and embarrassing proctological condition which can be very difficult to treat. We report the results of a double blind placebo controlled study of treatment with Capsaicin. Methods: Firstly, a pilot open study was carried out on five patients to establish which of two doses was the most acceptable by comparing effectiveness and side effects. Secondly, a double blind, placebo controlled, crossover study of topical Capsaicin was performed. This study involved two four week treatment phases separated by a one week washout phase. Forty four patients were randomised to receive locally either active Capsaicin (0.006%) or placebo (menthol 1%) ointment over a four week period (22 patients per group). After four weeks of treatment and a one week washout period, the placebo group began to receive Capsaicin while the treated group received placebo (menthol 1%) for another four weeks. At the end of the controlled study, responders from both groups continued with Capsaicin treatment in an open labelled manner. Results: Thirty one of 44 patients experienced relief during Capsaicin treatment periods and did not respond to menthol; all patients not responding to Capsaicin also failed on menthol (p<0.0001). In 13 patients, treatment with Capsaicin was unsuccessful: eight patients did not respond to Capsaicin treatment, one responded equally to Capsaicin and placebo, and four others dropped out because of side effects. During the follow up period (mean 10.9 (SD 5.8) months), 29 “responders” needed a mean application of Capsaicin every day (1.6 (SD 1.2); range 0.5–7 days) to remain symptom free (or nearly symptom free). Conclusion: Capsaicin is a new, safe, and highly effective treatment for severe intractable idiopathic pruritus ani.
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peri anal disease topical Capsaicin a novel and effective treatment for idiopathic intractable pruritus ani a randomised placebo controlled crossover study
2003Co-Authors: Joseph Lysy, D Keret, Yardena Israelit, Avigail Shmueli, M Sistieryittah, N Straussliviatan, Victoria Mindrul, Eran GoldinAbstract:Purpose: Pruritus ani is a common and embarrassing proctological condition which can be very difficult to treat. We report the results of a double blind placebo controlled study of treatment with Capsaicin. Methods: Firstly, a pilot open study was carried out on five patients to establish which of two doses was the most acceptable by comparing effectiveness and side effects. Secondly, a double blind, placebo controlled, crossover study of topical Capsaicin was performed. This study involved two four week treatment phases separated by a one week washout phase. Forty four patients were randomised to receive locally either active Capsaicin (0.006%) or placebo (menthol 1%) ointment over a four week period (22 patients per group). After four weeks of treatment and a one week washout period, the placebo group began to receive Capsaicin while the treated group received placebo (menthol 1%) for another four weeks. At the end of the controlled study, responders from both groups continued with Capsaicin treatment in an open labelled manner. Results: Thirty one of 44 patients experienced relief during Capsaicin treatment periods and did not respond to menthol; all patients not responding to Capsaicin also failed on menthol (p<0.0001). In 13 patients, treatment with Capsaicin was unsuccessful: eight patients did not respond to Capsaicin treatment, one responded equally to Capsaicin and placebo, and four others dropped out because of side effects. During the follow up period (mean 10.9 (SD 5.8) months), 29 “responders” needed a mean application of Capsaicin every day (1.6 (SD 1.2); range 0.5–7 days) to remain symptom free (or nearly symptom free). Conclusion: Capsaicin is a new, safe, and highly effective treatment for severe intractable idiopathic pruritus ani.
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topical Capsaicin is a novel and effective treatment for idiopathic intractable pruritus ani a randomized placebo controlled study
Gastroenterology, 2001Co-Authors: Joseph Lysy, Mima Sistieriittah, Yardena Israelit, Avigail Shmueli, Eran GoldinAbstract:Background: Pruritus ani is a common and embarrassing proctologic condition. The symptoms of idiopathic pruritus ani can be persistent and severe, and very difficult to treat. Capeaicin depletes Substance P from the peripheral neurons and is known to be effective in the treatment of pain, as well as of several itching cutaneous disorders, probable acting through this effect. Methods: A double-blind and placebo controlled study of topical Capsaicin in the treatment of idiopathic, intractable pruritus ani was carried out. Study Design: first, a pilot, open study was done on five patients to establish the best drug concentration. Secondly, 20 patients were randomized to receive locally either active(cepsaicin 0.006%) or placebo (white paraffin) ointement over a two month period. After the two months, the placebo group began to receive capssicin for two months, while the treated group continue the capeaicin t r e ~ only when symptoms recurred. Results: after the first two months, B patients in the treated group (80%) and none in the placebo group, were symptom free (p =0.005) Seven out of ten patients in the placebo group became symptom free when subsequently treated with capeain. Three patients dropped out because of perineal burning due to capeaicin, one in each treatment group and one in the pilot study group. During the four month follow up, "respooder" patients needed a mean single application of capseicin every four days to remain free of symptoms. Conclusions:Capsaicin is a new, safe and highly effective treatment for severe, inetractable idiopathic pruritus ani. Substance P probably plays a key role as a mediator in pruritus ani.
