Sex Dimorphism in Resolvin D5-induced Analgesia in Rat Models of Trigeminal Pain
•Antihyperalgesic effect of resolvin D5 (RvD5) on trigeminal neuropathic pain in females and males.•RvD5 decreased IL-6 levels only in male rats.•RvD5 reduced acute nociceptive and inflammatory pain only in male rats. Resolvin D5 (RvD5) is a specialized pro-resolving lipid mediator with potent anti-...
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| Veröffentlicht in: | The journal of pain 2023-05, Vol.24 (5), p.717-729 |
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| creator | Baggio, Darciane F. da Luz, Fernanda M.R. Lopes, Raphael V. Ferreira, Luiz E.N. Araya, Erika I. Chichorro, Juliana G. |
| description | •Antihyperalgesic effect of resolvin D5 (RvD5) on trigeminal neuropathic pain in females and males.•RvD5 decreased IL-6 levels only in male rats.•RvD5 reduced acute nociceptive and inflammatory pain only in male rats.
Resolvin D5 (RvD5) is a specialized pro-resolving lipid mediator with potent anti-inflammatory and analgesic properties. Orofacial pain conditions, especially those that are chronic, present clinical challenges in terms of pharmacological management. Thus, new therapeutic options are clearly warranted. Herein, we investigated the antinociceptive effect of RvD5 in the chronic constriction injury of the infraorbital nerve (CCI-ION) model and in the orofacial formalin test in female and male Wistar rats. Our results indicated that repeated subarachnoid medullary injections of RvD5 at 10 ng resulted in a significant reduction of heat and mechanical hyperalgesia induced by the CCI-ION in male and female rats, but males were more sensitive to RvD5 effects. In addition, after CCI-ION, interleukin-6 (IL-6) level was increased in the trigeminal nucleus caudalis of male, but not female rats, which was reduced by RvD5 repeated treatment. No changes in the levels of IL-1β were found. Minocycline blocked the effect of RvD5 in male rats but failed to affect RvD5 antinociceptive effect in females. Moreover, a single medullary injection of RvD5 caused a significant reduction of formalin-induced facial grooming, in phases I and II of the test, but only in male rats. This study demonstrated for the first time the analgesic effect of RvD5 in trigeminal pain models, and corroborated previous evidence of sex dichotomy, with a greater effect in males. This article presents a translational potential of RvD5 for targeted therapies aiming at the control of acute and chronic trigeminal pain, but further studies are needed to elucidate its sex-related mechanisms.
This study demonstrated that RvD5 may provide the benefits for trigeminal neuropathic pain treatment in male and female rats, but its effect on inflammatory orofacial pain seems to be restricted only to males. Also, it provided the evidence for sex dichotomy in the mechanisms related to the antinociceptive effect of RvD5.
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| doi_str_mv | 10.1016/j.jpain.2022.12.013 |
| format | Article |
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Resolvin D5 (RvD5) is a specialized pro-resolving lipid mediator with potent anti-inflammatory and analgesic properties. Orofacial pain conditions, especially those that are chronic, present clinical challenges in terms of pharmacological management. Thus, new therapeutic options are clearly warranted. Herein, we investigated the antinociceptive effect of RvD5 in the chronic constriction injury of the infraorbital nerve (CCI-ION) model and in the orofacial formalin test in female and male Wistar rats. Our results indicated that repeated subarachnoid medullary injections of RvD5 at 10 ng resulted in a significant reduction of heat and mechanical hyperalgesia induced by the CCI-ION in male and female rats, but males were more sensitive to RvD5 effects. In addition, after CCI-ION, interleukin-6 (IL-6) level was increased in the trigeminal nucleus caudalis of male, but not female rats, which was reduced by RvD5 repeated treatment. No changes in the levels of IL-1β were found. Minocycline blocked the effect of RvD5 in male rats but failed to affect RvD5 antinociceptive effect in females. Moreover, a single medullary injection of RvD5 caused a significant reduction of formalin-induced facial grooming, in phases I and II of the test, but only in male rats. This study demonstrated for the first time the analgesic effect of RvD5 in trigeminal pain models, and corroborated previous evidence of sex dichotomy, with a greater effect in males. This article presents a translational potential of RvD5 for targeted therapies aiming at the control of acute and chronic trigeminal pain, but further studies are needed to elucidate its sex-related mechanisms.
This study demonstrated that RvD5 may provide the benefits for trigeminal neuropathic pain treatment in male and female rats, but its effect on inflammatory orofacial pain seems to be restricted only to males. Also, it provided the evidence for sex dichotomy in the mechanisms related to the antinociceptive effect of RvD5.
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Resolvin D5 (RvD5) is a specialized pro-resolving lipid mediator with potent anti-inflammatory and analgesic properties. Orofacial pain conditions, especially those that are chronic, present clinical challenges in terms of pharmacological management. Thus, new therapeutic options are clearly warranted. Herein, we investigated the antinociceptive effect of RvD5 in the chronic constriction injury of the infraorbital nerve (CCI-ION) model and in the orofacial formalin test in female and male Wistar rats. Our results indicated that repeated subarachnoid medullary injections of RvD5 at 10 ng resulted in a significant reduction of heat and mechanical hyperalgesia induced by the CCI-ION in male and female rats, but males were more sensitive to RvD5 effects. In addition, after CCI-ION, interleukin-6 (IL-6) level was increased in the trigeminal nucleus caudalis of male, but not female rats, which was reduced by RvD5 repeated treatment. No changes in the levels of IL-1β were found. Minocycline blocked the effect of RvD5 in male rats but failed to affect RvD5 antinociceptive effect in females. Moreover, a single medullary injection of RvD5 caused a significant reduction of formalin-induced facial grooming, in phases I and II of the test, but only in male rats. This study demonstrated for the first time the analgesic effect of RvD5 in trigeminal pain models, and corroborated previous evidence of sex dichotomy, with a greater effect in males. This article presents a translational potential of RvD5 for targeted therapies aiming at the control of acute and chronic trigeminal pain, but further studies are needed to elucidate its sex-related mechanisms.
This study demonstrated that RvD5 may provide the benefits for trigeminal neuropathic pain treatment in male and female rats, but its effect on inflammatory orofacial pain seems to be restricted only to males. Also, it provided the evidence for sex dichotomy in the mechanisms related to the antinociceptive effect of RvD5.
[Display omitted]</description><subject>Analgesia</subject><subject>Analgesics - therapeutic use</subject><subject>Animals</subject><subject>Chronic Pain - drug therapy</subject><subject>Disease Models, Animal</subject><subject>Facial Pain - drug therapy</subject><subject>Female</subject><subject>Hyperalgesia - drug therapy</subject><subject>Hyperalgesia - etiology</subject><subject>interleukin 6</subject><subject>Male</subject><subject>orofacial formalin test</subject><subject>orofacial hyperalgesia</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Rats, Wistar</subject><subject>Sex Characteristics</subject><subject>specialized pro-resolving mediators</subject><subject>Trigeminal neuralgia</subject><issn>1526-5900</issn><issn>1528-8447</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kLtOAzEQRS0EghD4AiS0Jc0ufuza64IiSnhJICIIteW1J8HRPoKdRPD3OA8oqeYW586MDkIXBGcEE349z-YL7dqMYkozQjNM2AHqkYKWaZnn4nCbeVpIjE_QaQhzjAkphDhGJ4wXZS4Z6aHxG3wlI9d0fvHhQpO4NnmF0NXrGEZF6lq7MmCTQavrGQSnt4BeJs-dhTok3TSZeDeDxkUgGcd3ztDRVNcBzvezj97vbifDh_Tp5f5xOHhKDSvkMqU5lTy3usKWCSaJqUQphCk5VBYLhm2JK0ZyLATnUMpCUGkELStTaYy5pKyPrnZ7F777XEFYqsYFA3WtW-hWQVFRSMmppDyibIca34XgYaoW3jXafyuC1UalmqutSrVRqQhVUWVsXe4PrKoG7F_n110EbnZAFAFrB14F46CNupwHs1S2c_8e-AG7FoOQ</recordid><startdate>202305</startdate><enddate>202305</enddate><creator>Baggio, Darciane F.</creator><creator>da Luz, Fernanda M.R.</creator><creator>Lopes, Raphael V.</creator><creator>Ferreira, Luiz E.N.</creator><creator>Araya, Erika I.</creator><creator>Chichorro, Juliana G.</creator><general>Elsevier Inc</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>7X8</scope><orcidid>https://orcid.org/0000-0001-7957-2738</orcidid><orcidid>https://orcid.org/0000-0001-5345-141X</orcidid><orcidid>https://orcid.org/0000-0002-4882-5402</orcidid></search><sort><creationdate>202305</creationdate><title>Sex Dimorphism in Resolvin D5-induced Analgesia in Rat Models of Trigeminal Pain</title><author>Baggio, Darciane F. ; da Luz, Fernanda M.R. ; Lopes, Raphael V. ; Ferreira, Luiz E.N. ; Araya, Erika I. ; Chichorro, Juliana G.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c359t-242964dab0d37391cb7877c86ebd0730d80b31407766e895729c728bcba006923</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Analgesia</topic><topic>Analgesics - therapeutic use</topic><topic>Animals</topic><topic>Chronic Pain - drug therapy</topic><topic>Disease Models, Animal</topic><topic>Facial Pain - drug therapy</topic><topic>Female</topic><topic>Hyperalgesia - drug therapy</topic><topic>Hyperalgesia - etiology</topic><topic>interleukin 6</topic><topic>Male</topic><topic>orofacial formalin test</topic><topic>orofacial hyperalgesia</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Rats, Wistar</topic><topic>Sex Characteristics</topic><topic>specialized pro-resolving mediators</topic><topic>Trigeminal neuralgia</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Baggio, Darciane F.</creatorcontrib><creatorcontrib>da Luz, Fernanda M.R.</creatorcontrib><creatorcontrib>Lopes, Raphael V.</creatorcontrib><creatorcontrib>Ferreira, Luiz E.N.</creatorcontrib><creatorcontrib>Araya, Erika I.</creatorcontrib><creatorcontrib>Chichorro, Juliana G.</creatorcontrib><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>The journal of pain</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Baggio, Darciane F.</au><au>da Luz, Fernanda M.R.</au><au>Lopes, Raphael V.</au><au>Ferreira, Luiz E.N.</au><au>Araya, Erika I.</au><au>Chichorro, Juliana G.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Sex Dimorphism in Resolvin D5-induced Analgesia in Rat Models of Trigeminal Pain</atitle><jtitle>The journal of pain</jtitle><addtitle>J Pain</addtitle><date>2023-05</date><risdate>2023</risdate><volume>24</volume><issue>5</issue><spage>717</spage><epage>729</epage><pages>717-729</pages><issn>1526-5900</issn><eissn>1528-8447</eissn><abstract>•Antihyperalgesic effect of resolvin D5 (RvD5) on trigeminal neuropathic pain in females and males.•RvD5 decreased IL-6 levels only in male rats.•RvD5 reduced acute nociceptive and inflammatory pain only in male rats.
Resolvin D5 (RvD5) is a specialized pro-resolving lipid mediator with potent anti-inflammatory and analgesic properties. Orofacial pain conditions, especially those that are chronic, present clinical challenges in terms of pharmacological management. Thus, new therapeutic options are clearly warranted. Herein, we investigated the antinociceptive effect of RvD5 in the chronic constriction injury of the infraorbital nerve (CCI-ION) model and in the orofacial formalin test in female and male Wistar rats. Our results indicated that repeated subarachnoid medullary injections of RvD5 at 10 ng resulted in a significant reduction of heat and mechanical hyperalgesia induced by the CCI-ION in male and female rats, but males were more sensitive to RvD5 effects. In addition, after CCI-ION, interleukin-6 (IL-6) level was increased in the trigeminal nucleus caudalis of male, but not female rats, which was reduced by RvD5 repeated treatment. No changes in the levels of IL-1β were found. Minocycline blocked the effect of RvD5 in male rats but failed to affect RvD5 antinociceptive effect in females. Moreover, a single medullary injection of RvD5 caused a significant reduction of formalin-induced facial grooming, in phases I and II of the test, but only in male rats. This study demonstrated for the first time the analgesic effect of RvD5 in trigeminal pain models, and corroborated previous evidence of sex dichotomy, with a greater effect in males. This article presents a translational potential of RvD5 for targeted therapies aiming at the control of acute and chronic trigeminal pain, but further studies are needed to elucidate its sex-related mechanisms.
This study demonstrated that RvD5 may provide the benefits for trigeminal neuropathic pain treatment in male and female rats, but its effect on inflammatory orofacial pain seems to be restricted only to males. Also, it provided the evidence for sex dichotomy in the mechanisms related to the antinociceptive effect of RvD5.
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| subjects | Analgesia Analgesics - therapeutic use Animals Chronic Pain - drug therapy Disease Models, Animal Facial Pain - drug therapy Female Hyperalgesia - drug therapy Hyperalgesia - etiology interleukin 6 Male orofacial formalin test orofacial hyperalgesia Rats Rats, Sprague-Dawley Rats, Wistar Sex Characteristics specialized pro-resolving mediators Trigeminal neuralgia |
| title | Sex Dimorphism in Resolvin D5-induced Analgesia in Rat Models of Trigeminal Pain |
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