title: Hyaluronan modulates TRPV1 channel opening, reducing peripheral nociceptor activity and pain.
abstract: Hyaluronan (HA) is present in the extracellular matrix of all body tissues, including synovial fluid in joints, in which it behaves as a filter that buffers transmission of mechanical forces to nociceptor nerve endings thereby reducing pain. Using recombinant systems, mouse-cultured dorsal root ganglia (DRG) neurons and in vivo experiments, we found that HA also modulates polymodal transient receptor potential vanilloid subtype 1 (TRPV1) channels. HA diminishes heat, pH and capsaicin (CAP) responses, thus reducing the opening probability of the channel by stabilizing its closed state. Accordingly, in DRG neurons, HA decreases TRPV1-mediated impulse firing and channel sensitization by bradykinin. Moreover, subcutaneous HA injection in mice reduces heat and capsaicin nocifensive responses, whereas the intra-articular injection of HA in rats decreases capsaicin joint nociceptor fibres discharge. Collectively, these results indicate that extracellular HA reduces the excitability of the ubiquitous TRPV1 channel, thereby lowering impulse activity in the peripheral nociceptor endings underlying pain.
authors: Instituto de Neurociencias, Universidad Miguel Hernández-CSIC, San Juan de Alicante, 03550 Alicante, Spain.
authors: Rebeca
authors: R
authors: Caires
authors: Instituto de Neurociencias, Universidad Miguel Hernández-CSIC, San Juan de Alicante, 03550 Alicante, Spain.
authors: Enoch
authors: E
authors: Luis
authors: Instituto de Biología Molecular y Celular, Universidad Miguel Hernández, Elche, 03202 Alicante, Spain.
authors: Francisco J
authors: FJ
authors: Taberner
authors: Instituto de Biología Molecular y Celular, Universidad Miguel Hernández, Elche, 03202 Alicante, Spain.
authors: Gregorio
authors: G
authors: Fernandez-Ballester
authors: Instituto de Biología Molecular y Celular, Universidad Miguel Hernández, Elche, 03202 Alicante, Spain.
authors: Antonio
authors: A
authors: Ferrer-Montiel
authors: Matrix Biology Institute, 1040 Arcadian Way, Fort Lee, New Jersey 07024, USA.
authors: Endre A
authors: EA
authors: Balazs
authors: Instituto de Neurociencias, Universidad Miguel Hernández-CSIC, San Juan de Alicante, 03550 Alicante, Spain.
authors: Ana
authors: A
authors: Gomis
authors: Instituto de Neurociencias, Universidad Miguel Hernández-CSIC, San Juan de Alicante, 03550 Alicante, Spain.
authors: Carlos
authors: C
authors: Belmonte
authors: Instituto de Neurociencias, Universidad Miguel Hernández-CSIC, San Juan de Alicante, 03550 Alicante, Spain.
authors: Elvira
authors: E
authors: de la Peña
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001920:Bradykinin / Q000494:pharmacology; D016466:CHO Cells; D002118:Calcium / Q000378:metabolism; D002211:Capsaicin / Q000494:pharmacology; D045744:Cell Line, Tumor; D003412:Cricetulus; D005727:Ganglia, Spinal / Q000166:cytology; D057809:HEK293 Cells; D006358:Hot Temperature; D006801:Humans; D006820:Hyaluronic Acid / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008854:Microscopy, Electron; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D059226:Nociceptive Pain; D009619:Nociceptors / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D018689:Sensory System Agents / Q000494:pharmacology; D013264:Stifle / Q000187:drug effects* / Q000294:innervation; D000074025:TRPA1 Cation Channel; D050053:TRPM Cation Channels / Q000187:drug effects / Q000378:metabolism; D050916:TRPV Cation Channels / Q000187:drug effects* / Q000378:metabolism; D050051:Transient Receptor Potential Channels / Q000187:drug effects / Q000378:metabolism; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D000276:Adjuvants, Immunologic; D018689:Sensory System Agents; D000074025:TRPA1 Cation Channel; D050053:TRPM Cation Channels; C492297:TRPM8 protein, mouse; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; C493921:TRPV1 protein, mouse; D050051:Transient Receptor Potential Channels; C475685:Trpa1 protein, mouse; C493922:Trpv1 protein, rat; D014665:Vasodilator Agents; D006820:Hyaluronic Acid; D002211:Capsaicin; D001920:Bradykinin; D002118:Calcium