Bilateral analgesic effects of abobotulinumtoxinA (Dysport®) following unilateral administration in the rat
Background In addition to inhibition of muscle and glandular hyperactivity, botulinum neurotoxin (BoNT) type A also interferes with pain processing. Previously, in a rat model of paclitaxel‐induced polyneuropathy, abobotulinumtoxinA (aboBoNT‐A) elicited analgesic effects not only in the injected paw...
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| Veröffentlicht in: | European journal of pain 2017-05, Vol.21 (5), p.927-937 |
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| creator | Favre‐Guilmard, C. Chabrier, P.‐E. Kalinichev, M. |
| description | Background
In addition to inhibition of muscle and glandular hyperactivity, botulinum neurotoxin (BoNT) type A also interferes with pain processing. Previously, in a rat model of paclitaxel‐induced polyneuropathy, abobotulinumtoxinA (aboBoNT‐A) elicited analgesic effects not only in the injected paw, but also in the contralateral, non‐injected paw.
Methods
Here, we assessed bilateral analgesic effects of unilateral aboBoNT‐A in several chronic pain models in Sprague‐Dawley rats. Effects of aboBoNT‐A on the paw withdrawal threshold in response to mechanical pressure was assessed in models of streptozotocin‐induced diabetic polyneuropathy, chronic constriction injury (CCI)‐associated mononeuropathy, and bilateral carrageenan‐induced inflammatory pain.
Results
In diabetic polyneuropathy, aboBoNT‐A (15, 20 U/kg) reversed hyperalgesia in the toxin‐injected and non‐injected paws. In unilateral CCI‐exposed animals, 20 U/kg aboBoNT‐A given ipsilateral to the injury reversed mechanical hyperalgesia, while 30 U/kg aboBoNT‐A given contralateral to the injury had no effect. In carrageenan‐induced bilateral inflammatory pain, aboBoNT‐A (20, 30 U/kg) reversed hyperalgesia in both toxin‐injected and non‐injected paws.
Discussion
These results suggest that unilateral administration of aboBoNT‐A results in bilateral reduction in mechanical hyperalgesia across neuropathic and inflammatory pain conditions, bilateral activation of sensory neurons being prerequisite for its expression. Future studies involving effects on other sensory modalities as well as those evaluating diffusion and migration of the toxin away from the injection site can shed light on mechanisms of this phenomenon.
Significance
The results expand evidence on bilateral analgesic effects of aboBoNT‐A following unilateral administration across pain modalities, as the phenomenon is seen in more than one model of polyneuropathy as well as in a model of chronic inflammatory pain when the latter is rendered bilateral. The mechanism of bilateral analgesic effects of aboBoNT‐A may require activation of the peripheral sensory neurons and involve retrograde axonal transport of the toxin into the spinal cord. |
| doi_str_mv | 10.1002/ejp.995 |
| format | Article |
| fullrecord | <record><control><sourceid>wiley_cross</sourceid><recordid>TN_cdi_crossref_primary_10_1002_ejp_995</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>EJP995</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3175-35f03d16b4d7014b03dd1bf5bf347a59dd8f708ee39a2026aada83080690f1cc3</originalsourceid><addsrcrecordid>eNp1kEtOwzAURS0EoqUgdoA8A4RSnuN8h20pP1WCAYwjJ7aLK8eOYkelm2IRrIxU5TNi9N6Vjs7gIHRKYEwAwmuxasZ5Hu-hIYlpGIQkyvf7H3IIaAZkgI6cWwFAlAI9RIMwCxMKBIZIT5VmXrRMY2aYXgqnKiykFJV32ErMSlta32llutrbd2Um-OJm4xrb-s-PSyyt1natzBJ35k_Ea2WU8y3zyhqsDPZvAvfrGB1Ipp04-b4j9Ho7f5ndB4unu4fZZBFUlKRxQGMJlJOkjHgKJCr7wUkp41LSKGVxznkmU8iEoDkLIUwY4yyjkEGSgyRVRUfofOetWutcK2TRtKpm7aYgUGx7FX2vou_Vk2c7sunKWvBf7idQD1ztgLXSYvOfp5g_Pm91X3s7doQ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Bilateral analgesic effects of abobotulinumtoxinA (Dysport®) following unilateral administration in the rat</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><creator>Favre‐Guilmard, C. ; Chabrier, P.‐E. ; Kalinichev, M.</creator><creatorcontrib>Favre‐Guilmard, C. ; Chabrier, P.‐E. ; Kalinichev, M.</creatorcontrib><description>Background
In addition to inhibition of muscle and glandular hyperactivity, botulinum neurotoxin (BoNT) type A also interferes with pain processing. Previously, in a rat model of paclitaxel‐induced polyneuropathy, abobotulinumtoxinA (aboBoNT‐A) elicited analgesic effects not only in the injected paw, but also in the contralateral, non‐injected paw.
Methods
Here, we assessed bilateral analgesic effects of unilateral aboBoNT‐A in several chronic pain models in Sprague‐Dawley rats. Effects of aboBoNT‐A on the paw withdrawal threshold in response to mechanical pressure was assessed in models of streptozotocin‐induced diabetic polyneuropathy, chronic constriction injury (CCI)‐associated mononeuropathy, and bilateral carrageenan‐induced inflammatory pain.
Results
In diabetic polyneuropathy, aboBoNT‐A (15, 20 U/kg) reversed hyperalgesia in the toxin‐injected and non‐injected paws. In unilateral CCI‐exposed animals, 20 U/kg aboBoNT‐A given ipsilateral to the injury reversed mechanical hyperalgesia, while 30 U/kg aboBoNT‐A given contralateral to the injury had no effect. In carrageenan‐induced bilateral inflammatory pain, aboBoNT‐A (20, 30 U/kg) reversed hyperalgesia in both toxin‐injected and non‐injected paws.
Discussion
These results suggest that unilateral administration of aboBoNT‐A results in bilateral reduction in mechanical hyperalgesia across neuropathic and inflammatory pain conditions, bilateral activation of sensory neurons being prerequisite for its expression. Future studies involving effects on other sensory modalities as well as those evaluating diffusion and migration of the toxin away from the injection site can shed light on mechanisms of this phenomenon.
Significance
The results expand evidence on bilateral analgesic effects of aboBoNT‐A following unilateral administration across pain modalities, as the phenomenon is seen in more than one model of polyneuropathy as well as in a model of chronic inflammatory pain when the latter is rendered bilateral. The mechanism of bilateral analgesic effects of aboBoNT‐A may require activation of the peripheral sensory neurons and involve retrograde axonal transport of the toxin into the spinal cord.</description><identifier>ISSN: 1090-3801</identifier><identifier>EISSN: 1532-2149</identifier><identifier>DOI: 10.1002/ejp.995</identifier><identifier>PMID: 28263010</identifier><language>eng</language><publisher>England</publisher><subject>Analgesics - pharmacology ; Analgesics - therapeutic use ; Animals ; Botulinum Toxins, Type A - pharmacology ; Botulinum Toxins, Type A - therapeutic use ; Chronic Pain - drug therapy ; Chronic Pain - physiopathology ; Diabetic Neuropathies - drug therapy ; Diabetic Neuropathies - physiopathology ; Disease Models, Animal ; Hyperalgesia - drug therapy ; Hyperalgesia - physiopathology ; Inflammation - drug therapy ; Inflammation - physiopathology ; Male ; Pain Threshold - drug effects ; Pain Threshold - physiology ; Polyneuropathies - drug therapy ; Polyneuropathies - physiopathology ; Rats ; Rats, Sprague-Dawley ; Spinal Cord - drug effects ; Spinal Cord - physiopathology</subject><ispartof>European journal of pain, 2017-05, Vol.21 (5), p.927-937</ispartof><rights>2017 European Pain Federation ‐ EFIC</rights><rights>2017 European Pain Federation - EFIC®.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3175-35f03d16b4d7014b03dd1bf5bf347a59dd8f708ee39a2026aada83080690f1cc3</citedby><cites>FETCH-LOGICAL-c3175-35f03d16b4d7014b03dd1bf5bf347a59dd8f708ee39a2026aada83080690f1cc3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fejp.995$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fejp.995$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28263010$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Favre‐Guilmard, C.</creatorcontrib><creatorcontrib>Chabrier, P.‐E.</creatorcontrib><creatorcontrib>Kalinichev, M.</creatorcontrib><title>Bilateral analgesic effects of abobotulinumtoxinA (Dysport®) following unilateral administration in the rat</title><title>European journal of pain</title><addtitle>Eur J Pain</addtitle><description>Background
In addition to inhibition of muscle and glandular hyperactivity, botulinum neurotoxin (BoNT) type A also interferes with pain processing. Previously, in a rat model of paclitaxel‐induced polyneuropathy, abobotulinumtoxinA (aboBoNT‐A) elicited analgesic effects not only in the injected paw, but also in the contralateral, non‐injected paw.
Methods
Here, we assessed bilateral analgesic effects of unilateral aboBoNT‐A in several chronic pain models in Sprague‐Dawley rats. Effects of aboBoNT‐A on the paw withdrawal threshold in response to mechanical pressure was assessed in models of streptozotocin‐induced diabetic polyneuropathy, chronic constriction injury (CCI)‐associated mononeuropathy, and bilateral carrageenan‐induced inflammatory pain.
Results
In diabetic polyneuropathy, aboBoNT‐A (15, 20 U/kg) reversed hyperalgesia in the toxin‐injected and non‐injected paws. In unilateral CCI‐exposed animals, 20 U/kg aboBoNT‐A given ipsilateral to the injury reversed mechanical hyperalgesia, while 30 U/kg aboBoNT‐A given contralateral to the injury had no effect. In carrageenan‐induced bilateral inflammatory pain, aboBoNT‐A (20, 30 U/kg) reversed hyperalgesia in both toxin‐injected and non‐injected paws.
Discussion
These results suggest that unilateral administration of aboBoNT‐A results in bilateral reduction in mechanical hyperalgesia across neuropathic and inflammatory pain conditions, bilateral activation of sensory neurons being prerequisite for its expression. Future studies involving effects on other sensory modalities as well as those evaluating diffusion and migration of the toxin away from the injection site can shed light on mechanisms of this phenomenon.
Significance
The results expand evidence on bilateral analgesic effects of aboBoNT‐A following unilateral administration across pain modalities, as the phenomenon is seen in more than one model of polyneuropathy as well as in a model of chronic inflammatory pain when the latter is rendered bilateral. The mechanism of bilateral analgesic effects of aboBoNT‐A may require activation of the peripheral sensory neurons and involve retrograde axonal transport of the toxin into the spinal cord.</description><subject>Analgesics - pharmacology</subject><subject>Analgesics - therapeutic use</subject><subject>Animals</subject><subject>Botulinum Toxins, Type A - pharmacology</subject><subject>Botulinum Toxins, Type A - therapeutic use</subject><subject>Chronic Pain - drug therapy</subject><subject>Chronic Pain - physiopathology</subject><subject>Diabetic Neuropathies - drug therapy</subject><subject>Diabetic Neuropathies - physiopathology</subject><subject>Disease Models, Animal</subject><subject>Hyperalgesia - drug therapy</subject><subject>Hyperalgesia - physiopathology</subject><subject>Inflammation - drug therapy</subject><subject>Inflammation - physiopathology</subject><subject>Male</subject><subject>Pain Threshold - drug effects</subject><subject>Pain Threshold - physiology</subject><subject>Polyneuropathies - drug therapy</subject><subject>Polyneuropathies - physiopathology</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Spinal Cord - drug effects</subject><subject>Spinal Cord - physiopathology</subject><issn>1090-3801</issn><issn>1532-2149</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kEtOwzAURS0EoqUgdoA8A4RSnuN8h20pP1WCAYwjJ7aLK8eOYkelm2IRrIxU5TNi9N6Vjs7gIHRKYEwAwmuxasZ5Hu-hIYlpGIQkyvf7H3IIaAZkgI6cWwFAlAI9RIMwCxMKBIZIT5VmXrRMY2aYXgqnKiykFJV32ErMSlta32llutrbd2Um-OJm4xrb-s-PSyyt1natzBJ35k_Ea2WU8y3zyhqsDPZvAvfrGB1Ipp04-b4j9Ho7f5ndB4unu4fZZBFUlKRxQGMJlJOkjHgKJCr7wUkp41LSKGVxznkmU8iEoDkLIUwY4yyjkEGSgyRVRUfofOetWutcK2TRtKpm7aYgUGx7FX2vou_Vk2c7sunKWvBf7idQD1ztgLXSYvOfp5g_Pm91X3s7doQ</recordid><startdate>201705</startdate><enddate>201705</enddate><creator>Favre‐Guilmard, C.</creator><creator>Chabrier, P.‐E.</creator><creator>Kalinichev, M.</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope></search><sort><creationdate>201705</creationdate><title>Bilateral analgesic effects of abobotulinumtoxinA (Dysport®) following unilateral administration in the rat</title><author>Favre‐Guilmard, C. ; Chabrier, P.‐E. ; Kalinichev, M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3175-35f03d16b4d7014b03dd1bf5bf347a59dd8f708ee39a2026aada83080690f1cc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Analgesics - pharmacology</topic><topic>Analgesics - therapeutic use</topic><topic>Animals</topic><topic>Botulinum Toxins, Type A - pharmacology</topic><topic>Botulinum Toxins, Type A - therapeutic use</topic><topic>Chronic Pain - drug therapy</topic><topic>Chronic Pain - physiopathology</topic><topic>Diabetic Neuropathies - drug therapy</topic><topic>Diabetic Neuropathies - physiopathology</topic><topic>Disease Models, Animal</topic><topic>Hyperalgesia - drug therapy</topic><topic>Hyperalgesia - physiopathology</topic><topic>Inflammation - drug therapy</topic><topic>Inflammation - physiopathology</topic><topic>Male</topic><topic>Pain Threshold - drug effects</topic><topic>Pain Threshold - physiology</topic><topic>Polyneuropathies - drug therapy</topic><topic>Polyneuropathies - physiopathology</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Spinal Cord - drug effects</topic><topic>Spinal Cord - physiopathology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Favre‐Guilmard, C.</creatorcontrib><creatorcontrib>Chabrier, P.‐E.</creatorcontrib><creatorcontrib>Kalinichev, M.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>European journal of pain</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Favre‐Guilmard, C.</au><au>Chabrier, P.‐E.</au><au>Kalinichev, M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Bilateral analgesic effects of abobotulinumtoxinA (Dysport®) following unilateral administration in the rat</atitle><jtitle>European journal of pain</jtitle><addtitle>Eur J Pain</addtitle><date>2017-05</date><risdate>2017</risdate><volume>21</volume><issue>5</issue><spage>927</spage><epage>937</epage><pages>927-937</pages><issn>1090-3801</issn><eissn>1532-2149</eissn><abstract>Background
In addition to inhibition of muscle and glandular hyperactivity, botulinum neurotoxin (BoNT) type A also interferes with pain processing. Previously, in a rat model of paclitaxel‐induced polyneuropathy, abobotulinumtoxinA (aboBoNT‐A) elicited analgesic effects not only in the injected paw, but also in the contralateral, non‐injected paw.
Methods
Here, we assessed bilateral analgesic effects of unilateral aboBoNT‐A in several chronic pain models in Sprague‐Dawley rats. Effects of aboBoNT‐A on the paw withdrawal threshold in response to mechanical pressure was assessed in models of streptozotocin‐induced diabetic polyneuropathy, chronic constriction injury (CCI)‐associated mononeuropathy, and bilateral carrageenan‐induced inflammatory pain.
Results
In diabetic polyneuropathy, aboBoNT‐A (15, 20 U/kg) reversed hyperalgesia in the toxin‐injected and non‐injected paws. In unilateral CCI‐exposed animals, 20 U/kg aboBoNT‐A given ipsilateral to the injury reversed mechanical hyperalgesia, while 30 U/kg aboBoNT‐A given contralateral to the injury had no effect. In carrageenan‐induced bilateral inflammatory pain, aboBoNT‐A (20, 30 U/kg) reversed hyperalgesia in both toxin‐injected and non‐injected paws.
Discussion
These results suggest that unilateral administration of aboBoNT‐A results in bilateral reduction in mechanical hyperalgesia across neuropathic and inflammatory pain conditions, bilateral activation of sensory neurons being prerequisite for its expression. Future studies involving effects on other sensory modalities as well as those evaluating diffusion and migration of the toxin away from the injection site can shed light on mechanisms of this phenomenon.
Significance
The results expand evidence on bilateral analgesic effects of aboBoNT‐A following unilateral administration across pain modalities, as the phenomenon is seen in more than one model of polyneuropathy as well as in a model of chronic inflammatory pain when the latter is rendered bilateral. The mechanism of bilateral analgesic effects of aboBoNT‐A may require activation of the peripheral sensory neurons and involve retrograde axonal transport of the toxin into the spinal cord.</abstract><cop>England</cop><pmid>28263010</pmid><doi>10.1002/ejp.995</doi><tpages>11</tpages></addata></record> |
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| ispartof | European journal of pain, 2017-05, Vol.21 (5), p.927-937 |
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| source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | Analgesics - pharmacology Analgesics - therapeutic use Animals Botulinum Toxins, Type A - pharmacology Botulinum Toxins, Type A - therapeutic use Chronic Pain - drug therapy Chronic Pain - physiopathology Diabetic Neuropathies - drug therapy Diabetic Neuropathies - physiopathology Disease Models, Animal Hyperalgesia - drug therapy Hyperalgesia - physiopathology Inflammation - drug therapy Inflammation - physiopathology Male Pain Threshold - drug effects Pain Threshold - physiology Polyneuropathies - drug therapy Polyneuropathies - physiopathology Rats Rats, Sprague-Dawley Spinal Cord - drug effects Spinal Cord - physiopathology |
| title | Bilateral analgesic effects of abobotulinumtoxinA (Dysport®) following unilateral administration in the rat |
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