The effects of pregabalin and the glial attenuator minocycline on the response to intradermal capsaicin in patients with unilateral sciatica
Patients with unilateral sciatica have heightened responses to intradermal capsaicin compared to pain-free volunteers. No studies have investigated whether this pain model can screen for novel anti-neuropathic agents in patients with pre-existing neuropathic pain syndromes. This study compared the e...
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| description | Patients with unilateral sciatica have heightened responses to intradermal capsaicin compared to pain-free volunteers. No studies have investigated whether this pain model can screen for novel anti-neuropathic agents in patients with pre-existing neuropathic pain syndromes.
This study compared the effects of pregabalin (300 mg) and the tetracycline antibiotic and glial attenuator minocycline (400 mg) on capsaicin-induced spontaneous pain, flare, allodynia and hyperalgesia in patients with unilateral sciatica on both their affected and unaffected leg.
Eighteen patients with unilateral sciatica completed this randomised, double-blind, placebo-controlled, three-way cross-over study. Participants received a 10 µg dose of capsaicin into the middle section of their calf on both their affected and unaffected leg, separated by an interval of 75 min. Capsaicin-induced spontaneous pain, flare, allodynia and hyperalgesia were recorded pre-injection and at 5, 20, 40, 60 and 90 min post-injection. Minocycline tended to reduce pre-capsaicin injection values of hyperalgesia in the affected leg by 28% (95% CI 0% to 56%). The area under the effect time curves for capsaicin-induced spontaneous pain, flare, allodynia and hyperalgesia were not affected by either treatment compared to placebo. Significant limb differences were observed for flare (AUC) (-38% in affected leg, 95% CI for difference -19% to -52%). Both hand dominance and sex were significant covariates of response to capsaicin.
It cannot be concluded that minocycline is unsuitable for further evaluation as an anti-neuropathic pain drug as pregabalin, our positive control, failed to reduce capsaicin-induced neuropathic pain. However, the anti-hyperalgesic effect of minocycline observed pre-capsaicin injection is promising pilot information to support ongoing research into glial-mediated treatments for neuropathic pain. The differences in flare response between limbs may represent a useful biomarker to further investigate neuropathic pain. Inclusion of a positive control is imperative for the assessment of novel therapies for neuropathic pain. |
| doi_str_mv | 10.1371/journal.pone.0038525 |
| format | Article |
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This study compared the effects of pregabalin (300 mg) and the tetracycline antibiotic and glial attenuator minocycline (400 mg) on capsaicin-induced spontaneous pain, flare, allodynia and hyperalgesia in patients with unilateral sciatica on both their affected and unaffected leg.
Eighteen patients with unilateral sciatica completed this randomised, double-blind, placebo-controlled, three-way cross-over study. Participants received a 10 µg dose of capsaicin into the middle section of their calf on both their affected and unaffected leg, separated by an interval of 75 min. Capsaicin-induced spontaneous pain, flare, allodynia and hyperalgesia were recorded pre-injection and at 5, 20, 40, 60 and 90 min post-injection. Minocycline tended to reduce pre-capsaicin injection values of hyperalgesia in the affected leg by 28% (95% CI 0% to 56%). The area under the effect time curves for capsaicin-induced spontaneous pain, flare, allodynia and hyperalgesia were not affected by either treatment compared to placebo. Significant limb differences were observed for flare (AUC) (-38% in affected leg, 95% CI for difference -19% to -52%). Both hand dominance and sex were significant covariates of response to capsaicin.
It cannot be concluded that minocycline is unsuitable for further evaluation as an anti-neuropathic pain drug as pregabalin, our positive control, failed to reduce capsaicin-induced neuropathic pain. However, the anti-hyperalgesic effect of minocycline observed pre-capsaicin injection is promising pilot information to support ongoing research into glial-mediated treatments for neuropathic pain. The differences in flare response between limbs may represent a useful biomarker to further investigate neuropathic pain. Inclusion of a positive control is imperative for the assessment of novel therapies for neuropathic pain.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0038525</identifier><identifier>PMID: 22685578</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adult ; Analysis of Variance ; Antibiotics ; Biology ; Biomarkers ; Birth control ; Capsaicin ; Care and treatment ; Clinical trials ; Comparative analysis ; Cross-Over Studies ; Diabetes ; Discipline ; Double-Blind Method ; Drug dosages ; Drug Therapy, Combination ; Ethics ; Female ; gamma-Aminobutyric Acid - analogs & derivatives ; gamma-Aminobutyric Acid - therapeutic use ; Health care ; Hospitals ; Humans ; Hyperalgesia ; Hyperalgesia - chemically induced ; Hyperalgesia - physiopathology ; Hyperalgesia - prevention & control ; Injection ; Injections, Intradermal ; Leg ; Male ; Medical research ; Medicine ; Middle Aged ; Minocycline ; Minocycline - therapeutic use ; Nervous system ; Neuralgia ; Neuronal-glial interactions ; Neuropathy ; Pain ; Pain - chemically induced ; Pain - physiopathology ; Pain - prevention & control ; Pain management ; Pain perception ; Patients ; Phenols (Class of compounds) ; Pregabalin ; Sciatica ; Sciatica - drug therapy ; Sciatica - physiopathology ; Spinal cord injuries ; Time Factors ; Treatment Outcome ; Womens health</subject><ispartof>PloS one, 2012-06, Vol.7 (6), p.e38525</ispartof><rights>COPYRIGHT 2012 Public Library of Science</rights><rights>2012 Sumracki et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Sumracki et al. 2012</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-b9786640363ec88de78347ce1a180881e01a4930273ef4434ac8034c0236b7593</citedby><cites>FETCH-LOGICAL-c692t-b9786640363ec88de78347ce1a180881e01a4930273ef4434ac8034c0236b7593</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3369912/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3369912/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22685578$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sumracki, Nicole M</creatorcontrib><creatorcontrib>Hutchinson, Mark R</creatorcontrib><creatorcontrib>Gentgall, Melanie</creatorcontrib><creatorcontrib>Briggs, Nancy</creatorcontrib><creatorcontrib>Williams, Desmond B</creatorcontrib><creatorcontrib>Rolan, Paul</creatorcontrib><title>The effects of pregabalin and the glial attenuator minocycline on the response to intradermal capsaicin in patients with unilateral sciatica</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Patients with unilateral sciatica have heightened responses to intradermal capsaicin compared to pain-free volunteers. No studies have investigated whether this pain model can screen for novel anti-neuropathic agents in patients with pre-existing neuropathic pain syndromes.
This study compared the effects of pregabalin (300 mg) and the tetracycline antibiotic and glial attenuator minocycline (400 mg) on capsaicin-induced spontaneous pain, flare, allodynia and hyperalgesia in patients with unilateral sciatica on both their affected and unaffected leg.
Eighteen patients with unilateral sciatica completed this randomised, double-blind, placebo-controlled, three-way cross-over study. Participants received a 10 µg dose of capsaicin into the middle section of their calf on both their affected and unaffected leg, separated by an interval of 75 min. Capsaicin-induced spontaneous pain, flare, allodynia and hyperalgesia were recorded pre-injection and at 5, 20, 40, 60 and 90 min post-injection. Minocycline tended to reduce pre-capsaicin injection values of hyperalgesia in the affected leg by 28% (95% CI 0% to 56%). The area under the effect time curves for capsaicin-induced spontaneous pain, flare, allodynia and hyperalgesia were not affected by either treatment compared to placebo. Significant limb differences were observed for flare (AUC) (-38% in affected leg, 95% CI for difference -19% to -52%). Both hand dominance and sex were significant covariates of response to capsaicin.
It cannot be concluded that minocycline is unsuitable for further evaluation as an anti-neuropathic pain drug as pregabalin, our positive control, failed to reduce capsaicin-induced neuropathic pain. However, the anti-hyperalgesic effect of minocycline observed pre-capsaicin injection is promising pilot information to support ongoing research into glial-mediated treatments for neuropathic pain. The differences in flare response between limbs may represent a useful biomarker to further investigate neuropathic pain. Inclusion of a positive control is imperative for the assessment of novel therapies for neuropathic pain.</description><subject>Adult</subject><subject>Analysis of Variance</subject><subject>Antibiotics</subject><subject>Biology</subject><subject>Biomarkers</subject><subject>Birth control</subject><subject>Capsaicin</subject><subject>Care and treatment</subject><subject>Clinical trials</subject><subject>Comparative analysis</subject><subject>Cross-Over Studies</subject><subject>Diabetes</subject><subject>Discipline</subject><subject>Double-Blind Method</subject><subject>Drug dosages</subject><subject>Drug Therapy, Combination</subject><subject>Ethics</subject><subject>Female</subject><subject>gamma-Aminobutyric Acid - analogs & derivatives</subject><subject>gamma-Aminobutyric Acid - therapeutic use</subject><subject>Health care</subject><subject>Hospitals</subject><subject>Humans</subject><subject>Hyperalgesia</subject><subject>Hyperalgesia - chemically induced</subject><subject>Hyperalgesia - physiopathology</subject><subject>Hyperalgesia - prevention & control</subject><subject>Injection</subject><subject>Injections, Intradermal</subject><subject>Leg</subject><subject>Male</subject><subject>Medical research</subject><subject>Medicine</subject><subject>Middle Aged</subject><subject>Minocycline</subject><subject>Minocycline - therapeutic use</subject><subject>Nervous system</subject><subject>Neuralgia</subject><subject>Neuronal-glial interactions</subject><subject>Neuropathy</subject><subject>Pain</subject><subject>Pain - chemically induced</subject><subject>Pain - physiopathology</subject><subject>Pain - prevention & control</subject><subject>Pain management</subject><subject>Pain perception</subject><subject>Patients</subject><subject>Phenols (Class of compounds)</subject><subject>Pregabalin</subject><subject>Sciatica</subject><subject>Sciatica - drug therapy</subject><subject>Sciatica - physiopathology</subject><subject>Spinal cord 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effects of pregabalin and the glial attenuator minocycline on the response to intradermal capsaicin in patients with unilateral sciatica</title><author>Sumracki, Nicole M ; Hutchinson, Mark R ; Gentgall, Melanie ; Briggs, Nancy ; Williams, Desmond B ; Rolan, Paul</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-b9786640363ec88de78347ce1a180881e01a4930273ef4434ac8034c0236b7593</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Adult</topic><topic>Analysis of Variance</topic><topic>Antibiotics</topic><topic>Biology</topic><topic>Biomarkers</topic><topic>Birth control</topic><topic>Capsaicin</topic><topic>Care and treatment</topic><topic>Clinical trials</topic><topic>Comparative analysis</topic><topic>Cross-Over Studies</topic><topic>Diabetes</topic><topic>Discipline</topic><topic>Double-Blind Method</topic><topic>Drug dosages</topic><topic>Drug Therapy, 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One</addtitle><date>2012-06-07</date><risdate>2012</risdate><volume>7</volume><issue>6</issue><spage>e38525</spage><pages>e38525-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Patients with unilateral sciatica have heightened responses to intradermal capsaicin compared to pain-free volunteers. No studies have investigated whether this pain model can screen for novel anti-neuropathic agents in patients with pre-existing neuropathic pain syndromes.
This study compared the effects of pregabalin (300 mg) and the tetracycline antibiotic and glial attenuator minocycline (400 mg) on capsaicin-induced spontaneous pain, flare, allodynia and hyperalgesia in patients with unilateral sciatica on both their affected and unaffected leg.
Eighteen patients with unilateral sciatica completed this randomised, double-blind, placebo-controlled, three-way cross-over study. Participants received a 10 µg dose of capsaicin into the middle section of their calf on both their affected and unaffected leg, separated by an interval of 75 min. Capsaicin-induced spontaneous pain, flare, allodynia and hyperalgesia were recorded pre-injection and at 5, 20, 40, 60 and 90 min post-injection. Minocycline tended to reduce pre-capsaicin injection values of hyperalgesia in the affected leg by 28% (95% CI 0% to 56%). The area under the effect time curves for capsaicin-induced spontaneous pain, flare, allodynia and hyperalgesia were not affected by either treatment compared to placebo. Significant limb differences were observed for flare (AUC) (-38% in affected leg, 95% CI for difference -19% to -52%). Both hand dominance and sex were significant covariates of response to capsaicin.
It cannot be concluded that minocycline is unsuitable for further evaluation as an anti-neuropathic pain drug as pregabalin, our positive control, failed to reduce capsaicin-induced neuropathic pain. However, the anti-hyperalgesic effect of minocycline observed pre-capsaicin injection is promising pilot information to support ongoing research into glial-mediated treatments for neuropathic pain. The differences in flare response between limbs may represent a useful biomarker to further investigate neuropathic pain. Inclusion of a positive control is imperative for the assessment of novel therapies for neuropathic pain.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>22685578</pmid><doi>10.1371/journal.pone.0038525</doi><tpages>e38525</tpages><oa>free_for_read</oa></addata></record> |
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| recordid | cdi_plos_journals_1325024422 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Adult Analysis of Variance Antibiotics Biology Biomarkers Birth control Capsaicin Care and treatment Clinical trials Comparative analysis Cross-Over Studies Diabetes Discipline Double-Blind Method Drug dosages Drug Therapy, Combination Ethics Female gamma-Aminobutyric Acid - analogs & derivatives gamma-Aminobutyric Acid - therapeutic use Health care Hospitals Humans Hyperalgesia Hyperalgesia - chemically induced Hyperalgesia - physiopathology Hyperalgesia - prevention & control Injection Injections, Intradermal Leg Male Medical research Medicine Middle Aged Minocycline Minocycline - therapeutic use Nervous system Neuralgia Neuronal-glial interactions Neuropathy Pain Pain - chemically induced Pain - physiopathology Pain - prevention & control Pain management Pain perception Patients Phenols (Class of compounds) Pregabalin Sciatica Sciatica - drug therapy Sciatica - physiopathology Spinal cord injuries Time Factors Treatment Outcome Womens health |
| title | The effects of pregabalin and the glial attenuator minocycline on the response to intradermal capsaicin in patients with unilateral sciatica |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-06T23%3A24%3A36IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=The%20effects%20of%20pregabalin%20and%20the%20glial%20attenuator%20minocycline%20on%20the%20response%20to%20intradermal%20capsaicin%20in%20patients%20with%20unilateral%20sciatica&rft.jtitle=PloS%20one&rft.au=Sumracki,%20Nicole%20M&rft.date=2012-06-07&rft.volume=7&rft.issue=6&rft.spage=e38525&rft.pages=e38525-&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0038525&rft_dat=%3Cgale_plos_%3EA477115303%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1325024422&rft_id=info:pmid/22685578&rft_galeid=A477115303&rft_doaj_id=oai_doaj_org_article_e90d9338a4cb4f03a148f19684538e3d&rfr_iscdi=true |