In Vivo Calcium Imaging Visualizes Incision-Induced Primary Afferent Sensitization and Its Amelioration by Capsaicin Pretreatment

Previous studies have shown that infiltration of capsaicin into the surgical site can prevent incision-induced spontaneous pain like behaviors and heat hyperalgesia. In the present study, we aimed to monitor primary sensory neuron Ca activity in the intact dorsal root ganglia (DRG) using Pirt-GCaMP3...

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Veröffentlicht in:The Journal of neuroscience 2021-10, Vol.41 (41), p.8494-8507
Hauptverfasser: Ishida, Hirotake, Zhang, Yan, Gomez, Ruben, Shannonhouse, John, Son, Hyeonwi, Banik, Ratan, Kim, Yu Shin
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container_issue 41
container_start_page 8494
container_title The Journal of neuroscience
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creator Ishida, Hirotake
Zhang, Yan
Gomez, Ruben
Shannonhouse, John
Son, Hyeonwi
Banik, Ratan
Kim, Yu Shin
description Previous studies have shown that infiltration of capsaicin into the surgical site can prevent incision-induced spontaneous pain like behaviors and heat hyperalgesia. In the present study, we aimed to monitor primary sensory neuron Ca activity in the intact dorsal root ganglia (DRG) using Pirt-GCaMP3 male and female mice pretreated with capsaicin or vehicle before the plantar incision. Intraplantar injection of capsaicin (0.05%) significantly attenuated spontaneous pain, mechanical, and heat hypersensitivity after plantar incision. The Ca response in DRG and in spinal cord was significantly enhanced in the ipsilateral side compared with contralateral side or naive control. Primary sensory nerve fiber length was significantly decreased in the incision skin area in capsaicin-pretreated animals detected by immunohistochemistry and placental alkaline phosphatase (PLAP) staining. Thus, capsaicin pretreatment attenuates incisional pain by suppressing Ca response because of degeneration of primary sensory nerve fibers in the skin. Postoperative surgery pain is a major health and economic problem worldwide with ∼235 million major surgical procedures annually. Approximately 50% of these patients report uncontrolled or poorly controlled postoperative pain. However, mechanistic studies of postoperative surgery pain in primary sensory neurons have been limited to models or small numbers of neurons. Using an innovative, distinctive, and interdisciplinary populational dorsal root ganglia (DRG) imaging (>1800 neurons/DRG) approach, we revealed increased DRG neuronal Ca activity from postoperative pain mouse model. This indicates widespread DRG primary sensory neuron plasticity. Increased neuronal Ca activity occurs among various sizes of neurons but mostly in small-diameter and medium-diameter nociceptors. Capsaicin pretreatment as a therapeutic option significantly attenuates Ca activity and postoperative pain.
doi_str_mv 10.1523/JNEUROSCI.0457-21.2021
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In the present study, we aimed to monitor primary sensory neuron Ca activity in the intact dorsal root ganglia (DRG) using Pirt-GCaMP3 male and female mice pretreated with capsaicin or vehicle before the plantar incision. Intraplantar injection of capsaicin (0.05%) significantly attenuated spontaneous pain, mechanical, and heat hypersensitivity after plantar incision. The Ca response in DRG and in spinal cord was significantly enhanced in the ipsilateral side compared with contralateral side or naive control. Primary sensory nerve fiber length was significantly decreased in the incision skin area in capsaicin-pretreated animals detected by immunohistochemistry and placental alkaline phosphatase (PLAP) staining. Thus, capsaicin pretreatment attenuates incisional pain by suppressing Ca response because of degeneration of primary sensory nerve fibers in the skin. Postoperative surgery pain is a major health and economic problem worldwide with ∼235 million major surgical procedures annually. Approximately 50% of these patients report uncontrolled or poorly controlled postoperative pain. However, mechanistic studies of postoperative surgery pain in primary sensory neurons have been limited to models or small numbers of neurons. Using an innovative, distinctive, and interdisciplinary populational dorsal root ganglia (DRG) imaging (&gt;1800 neurons/DRG) approach, we revealed increased DRG neuronal Ca activity from postoperative pain mouse model. This indicates widespread DRG primary sensory neuron plasticity. Increased neuronal Ca activity occurs among various sizes of neurons but mostly in small-diameter and medium-diameter nociceptors. Capsaicin pretreatment as a therapeutic option significantly attenuates Ca activity and postoperative pain.</description><identifier>ISSN: 0270-6474</identifier><identifier>EISSN: 1529-2401</identifier><identifier>DOI: 10.1523/JNEUROSCI.0457-21.2021</identifier><identifier>PMID: 34452938</identifier><language>eng</language><publisher>United States: Society for Neuroscience</publisher><subject>Afferent Pathways - chemistry ; Afferent Pathways - drug effects ; Afferent Pathways - metabolism ; Alkaline phosphatase ; Animal models ; Animals ; Attenuation ; Calcium - metabolism ; Calcium imaging ; Calcium ions ; Capsaicin ; Capsaicin - administration &amp; dosage ; Degeneration ; Dorsal root ganglia ; Female ; Fibers ; Ganglia ; Ganglia, Spinal - chemistry ; Ganglia, Spinal - metabolism ; Hindlimb - innervation ; Hindlimb - metabolism ; Hyperalgesia - metabolism ; Hyperalgesia - prevention &amp; control ; Hypersensitivity ; Immunohistochemistry ; Male ; Mice ; Mice, Inbred C57BL ; Neurons ; Nociceptors ; Pain ; Pain perception ; Pain, Postoperative - metabolism ; Pain, Postoperative - prevention &amp; control ; Placental alkaline phosphatase ; Plantar Plate - chemistry ; Plantar Plate - innervation ; Plantar Plate - metabolism ; Pretreatment ; Sensory neurons ; Sensory System Agents - administration &amp; dosage ; Skin ; Spinal cord ; Surgery ; Surgical Wound - metabolism</subject><ispartof>The Journal of neuroscience, 2021-10, Vol.41 (41), p.8494-8507</ispartof><rights>Copyright © 2021 the authors.</rights><rights>Copyright Society for Neuroscience Oct 13, 2021</rights><rights>Copyright © 2021 the authors 2021</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c394t-1d74b1d658391cb4d79e57f578b8e7c348e7f94ee9ff14397abb60263b3d5db53</citedby><cites>FETCH-LOGICAL-c394t-1d74b1d658391cb4d79e57f578b8e7c348e7f94ee9ff14397abb60263b3d5db53</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/PMC8513701/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8513701/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34452938$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ishida, Hirotake</creatorcontrib><creatorcontrib>Zhang, Yan</creatorcontrib><creatorcontrib>Gomez, Ruben</creatorcontrib><creatorcontrib>Shannonhouse, John</creatorcontrib><creatorcontrib>Son, Hyeonwi</creatorcontrib><creatorcontrib>Banik, Ratan</creatorcontrib><creatorcontrib>Kim, Yu Shin</creatorcontrib><title>In Vivo Calcium Imaging Visualizes Incision-Induced Primary Afferent Sensitization and Its Amelioration by Capsaicin Pretreatment</title><title>The Journal of neuroscience</title><addtitle>J Neurosci</addtitle><description>Previous studies have shown that infiltration of capsaicin into the surgical site can prevent incision-induced spontaneous pain like behaviors and heat hyperalgesia. In the present study, we aimed to monitor primary sensory neuron Ca activity in the intact dorsal root ganglia (DRG) using Pirt-GCaMP3 male and female mice pretreated with capsaicin or vehicle before the plantar incision. Intraplantar injection of capsaicin (0.05%) significantly attenuated spontaneous pain, mechanical, and heat hypersensitivity after plantar incision. The Ca response in DRG and in spinal cord was significantly enhanced in the ipsilateral side compared with contralateral side or naive control. Primary sensory nerve fiber length was significantly decreased in the incision skin area in capsaicin-pretreated animals detected by immunohistochemistry and placental alkaline phosphatase (PLAP) staining. Thus, capsaicin pretreatment attenuates incisional pain by suppressing Ca response because of degeneration of primary sensory nerve fibers in the skin. Postoperative surgery pain is a major health and economic problem worldwide with ∼235 million major surgical procedures annually. Approximately 50% of these patients report uncontrolled or poorly controlled postoperative pain. However, mechanistic studies of postoperative surgery pain in primary sensory neurons have been limited to models or small numbers of neurons. Using an innovative, distinctive, and interdisciplinary populational dorsal root ganglia (DRG) imaging (&gt;1800 neurons/DRG) approach, we revealed increased DRG neuronal Ca activity from postoperative pain mouse model. This indicates widespread DRG primary sensory neuron plasticity. Increased neuronal Ca activity occurs among various sizes of neurons but mostly in small-diameter and medium-diameter nociceptors. 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control</subject><subject>Placental alkaline phosphatase</subject><subject>Plantar Plate - chemistry</subject><subject>Plantar Plate - innervation</subject><subject>Plantar Plate - metabolism</subject><subject>Pretreatment</subject><subject>Sensory neurons</subject><subject>Sensory System Agents - administration &amp; dosage</subject><subject>Skin</subject><subject>Spinal cord</subject><subject>Surgery</subject><subject>Surgical Wound - metabolism</subject><issn>0270-6474</issn><issn>1529-2401</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkctu1DAUhi0EotPCK1SW2LDJ4GucbJBGo0KDKoooZWv5lsFVYg92Uqnd9c3r0bSjwsaWzvnOfy4_AKcYLTEn9NO372fXPy-v1t0SMS4qgpcEEfwKLEq2rQhD-DVYICJQVTPBjsBxzjcIIYGweAuOKGMFo80CPHQB_va3Ea7VYPw8wm5UGx82JZhnNfh7l2EXjM8-hqoLdjbOwh_JjyrdwVXfu-TCBK9cyH7y92oqGFTBwm7KcDW6wce0D-q70mKblTc-FAE3JaemsRS_A296NWT3_uk_Addfzn6tz6uLy6_denVRGdqyqcJWMI1tzRvaYqOZFa3jouei0Y0ThrLy9i1zru17zGgrlNY1IjXV1HKrOT0Bn_e621mPzprSOqlBbve7yKi8_DcT_B-5ibey4ZiWuxWBj08CKf6dXZ7k6LNxw6CCi3OWhNc1KoenO_TDf-hNnFMo6xWqobxFQrBC1XvKpJhzcv1hGIzkzmV5cFnuXJYEy53LpfD05SqHsmdb6SOix6bg</recordid><startdate>20211013</startdate><enddate>20211013</enddate><creator>Ishida, Hirotake</creator><creator>Zhang, Yan</creator><creator>Gomez, Ruben</creator><creator>Shannonhouse, John</creator><creator>Son, Hyeonwi</creator><creator>Banik, Ratan</creator><creator>Kim, Yu Shin</creator><general>Society for Neuroscience</general><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>7QG</scope><scope>7QR</scope><scope>7TK</scope><scope>7U7</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20211013</creationdate><title>In Vivo Calcium Imaging Visualizes Incision-Induced Primary Afferent Sensitization and Its Amelioration by Capsaicin Pretreatment</title><author>Ishida, Hirotake ; 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Capsaicin pretreatment as a therapeutic option significantly attenuates Ca activity and postoperative pain.</abstract><cop>United States</cop><pub>Society for Neuroscience</pub><pmid>34452938</pmid><doi>10.1523/JNEUROSCI.0457-21.2021</doi><tpages>14</tpages></addata></record>
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subjects Afferent Pathways - chemistry
Afferent Pathways - drug effects
Afferent Pathways - metabolism
Alkaline phosphatase
Animal models
Animals
Attenuation
Calcium - metabolism
Calcium imaging
Calcium ions
Capsaicin
Capsaicin - administration & dosage
Degeneration
Dorsal root ganglia
Female
Fibers
Ganglia
Ganglia, Spinal - chemistry
Ganglia, Spinal - metabolism
Hindlimb - innervation
Hindlimb - metabolism
Hyperalgesia - metabolism
Hyperalgesia - prevention & control
Hypersensitivity
Immunohistochemistry
Male
Mice
Mice, Inbred C57BL
Neurons
Nociceptors
Pain
Pain perception
Pain, Postoperative - metabolism
Pain, Postoperative - prevention & control
Placental alkaline phosphatase
Plantar Plate - chemistry
Plantar Plate - innervation
Plantar Plate - metabolism
Pretreatment
Sensory neurons
Sensory System Agents - administration & dosage
Skin
Spinal cord
Surgery
Surgical Wound - metabolism
title In Vivo Calcium Imaging Visualizes Incision-Induced Primary Afferent Sensitization and Its Amelioration by Capsaicin Pretreatment
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