The antiallodynic effects of Intrathecal cholinesterase inhibitors in a rat model of neuropathic pain
This study determined the effect of intrathecally administered cholinesterase inhibitors, edrophonium and neostigmine, on nerve injury-induced, touch-evoked allodynia and identified the pharmacologic characteristics of this action. Rats were prepared with tight ligation of the left L5 and L6 spinal...
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| Veröffentlicht in: | Anesthesiology (Philadelphia) 1999-02, Vol.90 (2), p.492-499 |
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| creator | HWANG, J.-H HWANG, K.-S LEEM, J.-K PARK, P.-H HAN, S.-M LEE, D.-M |
| description | This study determined the effect of intrathecally administered cholinesterase inhibitors, edrophonium and neostigmine, on nerve injury-induced, touch-evoked allodynia and identified the pharmacologic characteristics of this action.
Rats were prepared with tight ligation of the left L5 and L6 spinal nerves and with lumbar intrathecal catheters fitted for long-term monitoring. Edrophonium (3, 10, 30, or 100 microg) or neostigmine (0.3, 1, 3, or 10 microg) was administered intrathecally. Tactile allodynia and motor weakness were assessed. To evaluate the pharmacologic characteristics of the activity, a muscarinic receptor antagonist or a nicotinic receptor antagonist was administered intrathecally before edrophonium or neostigmine was injected. To compare the action of subtype antagonists, the M1 muscarinic receptor antagonist pirenzepine, the M2 antagonist methoctramine, the M3 antagonist 4-DAMP (diphenylacetoxy-N-methypiperidine), and the M4 antagonist tropicamide were administered intrathecally before cholinesterase inhibitors were injected.
Intrathecal edrophonium or neostigmine produced a dose-dependent antagonism of the touch-evoked allodynia. Neostigmine resulted in a moderate effect on motor weakness at doses of 3 and 10 microg. Pretreatment with intrathecal atropine but not mecamylamine yielded a complete antagonism of the effects of the cholinesterase inhibitors. In addition, antiallodynia produced by edrophonium (100 microg) was reversed by pretreatment with methoctramine, 4-DAMP, tropicamide, and pirenzepine. In the neostigmine (10 microg) group, only the M1 antagonist pirenzepine had a moderate effect on reversal of increased allodynic threshold.
These experiments suggest that intrathecal edrophonium or neostigmine produces an antagonism on touch-evoked allodynia at the spinal level in a rat model of neuropathic pain and that the antiallodynic action of cholinesterase inhibitors is probably mediated by a spinal muscarinic system, especially at the M1 receptor subtype. |
| doi_str_mv | 10.1097/00000542-199902000-00025 |
| format | Article |
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Rats were prepared with tight ligation of the left L5 and L6 spinal nerves and with lumbar intrathecal catheters fitted for long-term monitoring. Edrophonium (3, 10, 30, or 100 microg) or neostigmine (0.3, 1, 3, or 10 microg) was administered intrathecally. Tactile allodynia and motor weakness were assessed. To evaluate the pharmacologic characteristics of the activity, a muscarinic receptor antagonist or a nicotinic receptor antagonist was administered intrathecally before edrophonium or neostigmine was injected. To compare the action of subtype antagonists, the M1 muscarinic receptor antagonist pirenzepine, the M2 antagonist methoctramine, the M3 antagonist 4-DAMP (diphenylacetoxy-N-methypiperidine), and the M4 antagonist tropicamide were administered intrathecally before cholinesterase inhibitors were injected.
Intrathecal edrophonium or neostigmine produced a dose-dependent antagonism of the touch-evoked allodynia. Neostigmine resulted in a moderate effect on motor weakness at doses of 3 and 10 microg. Pretreatment with intrathecal atropine but not mecamylamine yielded a complete antagonism of the effects of the cholinesterase inhibitors. In addition, antiallodynia produced by edrophonium (100 microg) was reversed by pretreatment with methoctramine, 4-DAMP, tropicamide, and pirenzepine. In the neostigmine (10 microg) group, only the M1 antagonist pirenzepine had a moderate effect on reversal of increased allodynic threshold.
These experiments suggest that intrathecal edrophonium or neostigmine produces an antagonism on touch-evoked allodynia at the spinal level in a rat model of neuropathic pain and that the antiallodynic action of cholinesterase inhibitors is probably mediated by a spinal muscarinic system, especially at the M1 receptor subtype.</description><identifier>ISSN: 0003-3022</identifier><identifier>EISSN: 1528-1175</identifier><identifier>DOI: 10.1097/00000542-199902000-00025</identifier><identifier>PMID: 9952157</identifier><identifier>CODEN: ANESAV</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott</publisher><subject><![CDATA[Analgesics ; Animals ; Biological and medical sciences ; Cholinesterase Inhibitors - administration & dosage ; Edrophonium - administration & dosage ; Injections, Spinal ; Male ; Medical sciences ; Muscarinic Agonists - administration & dosage ; Muscarinic Antagonists - administration & dosage ; Neostigmine - administration & dosage ; Neuralgia - drug therapy ; Neuralgia - physiopathology ; Neuropharmacology ; Parasympathomimetics - administration & dosage ; Pharmacology. Drug treatments ; Rats ; Rats, Sprague-Dawley ; Receptors, Muscarinic - physiology]]></subject><ispartof>Anesthesiology (Philadelphia), 1999-02, Vol.90 (2), p.492-499</ispartof><rights>1999 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c405t-5a1615e27b4d5543b53851cf86d848fbda46c3adfcbb22c65ae10e0730cade913</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,781,785,27926,27927</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1687515$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9952157$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>HWANG, J.-H</creatorcontrib><creatorcontrib>HWANG, K.-S</creatorcontrib><creatorcontrib>LEEM, J.-K</creatorcontrib><creatorcontrib>PARK, P.-H</creatorcontrib><creatorcontrib>HAN, S.-M</creatorcontrib><creatorcontrib>LEE, D.-M</creatorcontrib><title>The antiallodynic effects of Intrathecal cholinesterase inhibitors in a rat model of neuropathic pain</title><title>Anesthesiology (Philadelphia)</title><addtitle>Anesthesiology</addtitle><description>This study determined the effect of intrathecally administered cholinesterase inhibitors, edrophonium and neostigmine, on nerve injury-induced, touch-evoked allodynia and identified the pharmacologic characteristics of this action.
Rats were prepared with tight ligation of the left L5 and L6 spinal nerves and with lumbar intrathecal catheters fitted for long-term monitoring. Edrophonium (3, 10, 30, or 100 microg) or neostigmine (0.3, 1, 3, or 10 microg) was administered intrathecally. Tactile allodynia and motor weakness were assessed. To evaluate the pharmacologic characteristics of the activity, a muscarinic receptor antagonist or a nicotinic receptor antagonist was administered intrathecally before edrophonium or neostigmine was injected. To compare the action of subtype antagonists, the M1 muscarinic receptor antagonist pirenzepine, the M2 antagonist methoctramine, the M3 antagonist 4-DAMP (diphenylacetoxy-N-methypiperidine), and the M4 antagonist tropicamide were administered intrathecally before cholinesterase inhibitors were injected.
Intrathecal edrophonium or neostigmine produced a dose-dependent antagonism of the touch-evoked allodynia. Neostigmine resulted in a moderate effect on motor weakness at doses of 3 and 10 microg. Pretreatment with intrathecal atropine but not mecamylamine yielded a complete antagonism of the effects of the cholinesterase inhibitors. In addition, antiallodynia produced by edrophonium (100 microg) was reversed by pretreatment with methoctramine, 4-DAMP, tropicamide, and pirenzepine. In the neostigmine (10 microg) group, only the M1 antagonist pirenzepine had a moderate effect on reversal of increased allodynic threshold.
These experiments suggest that intrathecal edrophonium or neostigmine produces an antagonism on touch-evoked allodynia at the spinal level in a rat model of neuropathic pain and that the antiallodynic action of cholinesterase inhibitors is probably mediated by a spinal muscarinic system, especially at the M1 receptor subtype.</description><subject>Analgesics</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Cholinesterase Inhibitors - administration & dosage</subject><subject>Edrophonium - administration & dosage</subject><subject>Injections, Spinal</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Muscarinic Agonists - administration & dosage</subject><subject>Muscarinic Antagonists - administration & dosage</subject><subject>Neostigmine - administration & dosage</subject><subject>Neuralgia - drug therapy</subject><subject>Neuralgia - physiopathology</subject><subject>Neuropharmacology</subject><subject>Parasympathomimetics - administration & dosage</subject><subject>Pharmacology. Drug treatments</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Receptors, Muscarinic - physiology</subject><issn>0003-3022</issn><issn>1528-1175</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1999</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkFtLxDAQhYMoul5-gpAH8a2aS6dtHkW8geCLPpdpOmEj3WRNug_-e7O6aiAkkznnZPgY41JcSWHaa7FdUKtKGmOEKkVVtoI9tpCgukrKFvbZorzpSguljthxzu-lbEF3h-zQGFAS2gWj1yVxDLPHaYrjZ_CWk3Nk58yj409hTjgvyeLE7TJOPlCeKWEm7sPSD36OKZcrR150fBVHmra-QJsU18VZ4tbowyk7cDhlOtudJ-zt_u719rF6fnl4ur15rmwtYK4AZSOBVDvUI0CthzIsSOu6Zuzqzg0j1o3VODo7DErZBpCkINFqYXEkI_UJu_zJXaf4sSmz9iufLU0TBoqb3DcGmrYxugi7H6FNMedErl8nv8L02UvRbwn3v4T7P8L9N-FiPd_9sRlWNP4Zd0hL_2LXx1y4uYTB-vyf33QtSNBfYUqErw</recordid><startdate>19990201</startdate><enddate>19990201</enddate><creator>HWANG, J.-H</creator><creator>HWANG, K.-S</creator><creator>LEEM, J.-K</creator><creator>PARK, P.-H</creator><creator>HAN, S.-M</creator><creator>LEE, D.-M</creator><general>Lippincott</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>19990201</creationdate><title>The antiallodynic effects of Intrathecal cholinesterase inhibitors in a rat model of neuropathic pain</title><author>HWANG, J.-H ; HWANG, K.-S ; LEEM, J.-K ; PARK, P.-H ; HAN, S.-M ; LEE, D.-M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c405t-5a1615e27b4d5543b53851cf86d848fbda46c3adfcbb22c65ae10e0730cade913</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1999</creationdate><topic>Analgesics</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Cholinesterase Inhibitors - administration & dosage</topic><topic>Edrophonium - administration & dosage</topic><topic>Injections, Spinal</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Muscarinic Agonists - administration & dosage</topic><topic>Muscarinic Antagonists - administration & dosage</topic><topic>Neostigmine - administration & dosage</topic><topic>Neuralgia - drug therapy</topic><topic>Neuralgia - physiopathology</topic><topic>Neuropharmacology</topic><topic>Parasympathomimetics - administration & dosage</topic><topic>Pharmacology. Drug treatments</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Receptors, Muscarinic - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>HWANG, J.-H</creatorcontrib><creatorcontrib>HWANG, K.-S</creatorcontrib><creatorcontrib>LEEM, J.-K</creatorcontrib><creatorcontrib>PARK, P.-H</creatorcontrib><creatorcontrib>HAN, S.-M</creatorcontrib><creatorcontrib>LEE, D.-M</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Anesthesiology (Philadelphia)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>HWANG, J.-H</au><au>HWANG, K.-S</au><au>LEEM, J.-K</au><au>PARK, P.-H</au><au>HAN, S.-M</au><au>LEE, D.-M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The antiallodynic effects of Intrathecal cholinesterase inhibitors in a rat model of neuropathic pain</atitle><jtitle>Anesthesiology (Philadelphia)</jtitle><addtitle>Anesthesiology</addtitle><date>1999-02-01</date><risdate>1999</risdate><volume>90</volume><issue>2</issue><spage>492</spage><epage>499</epage><pages>492-499</pages><issn>0003-3022</issn><eissn>1528-1175</eissn><coden>ANESAV</coden><abstract>This study determined the effect of intrathecally administered cholinesterase inhibitors, edrophonium and neostigmine, on nerve injury-induced, touch-evoked allodynia and identified the pharmacologic characteristics of this action.
Rats were prepared with tight ligation of the left L5 and L6 spinal nerves and with lumbar intrathecal catheters fitted for long-term monitoring. Edrophonium (3, 10, 30, or 100 microg) or neostigmine (0.3, 1, 3, or 10 microg) was administered intrathecally. Tactile allodynia and motor weakness were assessed. To evaluate the pharmacologic characteristics of the activity, a muscarinic receptor antagonist or a nicotinic receptor antagonist was administered intrathecally before edrophonium or neostigmine was injected. To compare the action of subtype antagonists, the M1 muscarinic receptor antagonist pirenzepine, the M2 antagonist methoctramine, the M3 antagonist 4-DAMP (diphenylacetoxy-N-methypiperidine), and the M4 antagonist tropicamide were administered intrathecally before cholinesterase inhibitors were injected.
Intrathecal edrophonium or neostigmine produced a dose-dependent antagonism of the touch-evoked allodynia. Neostigmine resulted in a moderate effect on motor weakness at doses of 3 and 10 microg. Pretreatment with intrathecal atropine but not mecamylamine yielded a complete antagonism of the effects of the cholinesterase inhibitors. In addition, antiallodynia produced by edrophonium (100 microg) was reversed by pretreatment with methoctramine, 4-DAMP, tropicamide, and pirenzepine. In the neostigmine (10 microg) group, only the M1 antagonist pirenzepine had a moderate effect on reversal of increased allodynic threshold.
These experiments suggest that intrathecal edrophonium or neostigmine produces an antagonism on touch-evoked allodynia at the spinal level in a rat model of neuropathic pain and that the antiallodynic action of cholinesterase inhibitors is probably mediated by a spinal muscarinic system, especially at the M1 receptor subtype.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott</pub><pmid>9952157</pmid><doi>10.1097/00000542-199902000-00025</doi><tpages>8</tpages></addata></record> |
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| subjects | Analgesics Animals Biological and medical sciences Cholinesterase Inhibitors - administration & dosage Edrophonium - administration & dosage Injections, Spinal Male Medical sciences Muscarinic Agonists - administration & dosage Muscarinic Antagonists - administration & dosage Neostigmine - administration & dosage Neuralgia - drug therapy Neuralgia - physiopathology Neuropharmacology Parasympathomimetics - administration & dosage Pharmacology. Drug treatments Rats Rats, Sprague-Dawley Receptors, Muscarinic - physiology |
| title | The antiallodynic effects of Intrathecal cholinesterase inhibitors in a rat model of neuropathic pain |
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