Journal article
Second messengers mediating high-molecular-weight hyaluronan-induced antihyperalgesia in rats with chemotherapy-induced peripheral neuropathy
Pain (Amsterdam), Vol.163(9), pp.1728-1739
09/01/2022
DOI: 10.1097/j.pain.0000000000002558
PMID: 34913881
Abstract
High-molecular-weight hyaluronan (HMWH) is an agonist at cluster of differentiation (CD)44, the cognate hyaluronan receptor, on nociceptors, where it acts to induce antihyperalgesia in preclinical models of inflammatory and neuropathic pain. In the present experiments, we studied the CD44 second messengers that mediate HMWH-induced attenuation of pain associated with oxaliplatin and paclitaxel chemotherapy-induced peripheral neuropathy (CIPN). While HMWH attenuated CIPN only in male rats, after ovariectomy or intrathecal administration of an oligodeoxynucleotide (ODN) antisense to G protein–coupled estrogen receptor (GPR30) mRNA, female rats were also sensitive to HMWH. Intrathecal administration of an ODN antisense to CD44 mRNA markedly attenuated HMWH-induced antihyperalgesia in male rats with CIPN induced by oxaliplatin or paclitaxel. Intradermal administration of inhibitors of CD44 second messengers, RhoA (member of the Rho family of GTPases), phospholipase C, and phosphatidylinositol (PI) 3-kinase gamma (PI3Kγ), attenuated HMWH-induced antihyperalgesia as does intrathecal administration of an ODN antisense to PI3Kγ. Our results demonstrated that HMWH induced antihyperalgesia in CIPN, mediated by its action at CD44 and downstream signaling by RhoA, phospholipase C, and PI3Kγ.
Details
- Title: Subtitle
- Second messengers mediating high-molecular-weight hyaluronan-induced antihyperalgesia in rats with chemotherapy-induced peripheral neuropathy
- Creators
- Ivan J.M. Bonet - University of California, San FranciscoLarissa Staurengo-Ferrari - University of California, San FranciscoDionéia Araldi - University of California, San FranciscoPaul G. Green - University of California, San FranciscoJon D. Levine - University of California, San Francisco
- Resource Type
- Journal article
- Publication Details
- Pain (Amsterdam), Vol.163(9), pp.1728-1739
- DOI
- 10.1097/j.pain.0000000000002558
- PMID
- 34913881
- ISSN
- 0304-3959
- eISSN
- 1872-6623
- Number of pages
- 12
- Grant note
- CA250017 / National Institutes of Health (http://data.elsevier.com/vocabulary/SciValFunders/100000002) R01AR075334 / National Institute of Arthritis and Musculoskeletal and Skin Diseases (http://data.elsevier.com/vocabulary/SciValFunders/100000069)
- Language
- English
- Date published
- 09/01/2022
- Academic Unit
- Neuroscience and Pharmacology
- Record Identifier
- 9985178662102771
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