title: Endovanilloid control of pain modulation by the rostroventromedial medulla in an animal model of diabetic neuropathy.
abstract: The involvement of transient receptor vanilloid type-1 (TRPV1) channels in pain modulation by the brain remains understudied. The rostroventromedial medulla (RVM) plays a key role in conveying to the spinal cord pain modulatory influences triggered in higher brain centres, with co-existence of inhibitory (antinociceptive) and facilitatory (pronociceptive) effects. In spite of some reports of TRPV1 expression in the RVM, it remains unknown if endovanilloid signalling plays a direct role in local pain modulation. Here we used a model of diabetic neuropathy, the streptozotocin (STZ)-diabetic rat, to study the role of endovanilloid signalling in RVM-mediated pain modulation during chronic pain. Four weeks after diabetes induction, the levels of TRPV1 mRNA and fatty acid amide hydrolase (FAAH), a crucial enzyme for endovanilloid catabolism, in the RVM of STZ-diabetic rats were higher than control. The RVM of STZ-diabetic rats presented decreased levels of several TRPV1 endogenous ligands, namely anandamide (AEA), palmitoylethanolamide (PEA) and oleoylethanolamide (OEA). Administration of capsaicin (a TRPV1 agonist) into the RVM decreased nociceptive behavioural responses in the inflammatory phase of the formalin test (phase 2). These findings suggest that diabetic neuropathy induces plastic changes of RVM endovanilloid signalling, indicating that TRPV1 may be a putative target for pain modulation in this chronic pain condition.
authors.affiliation: Departamento de Biologia Experimental, Faculdade de Medicina, Universidade do Porto, Portugal; I3S - Instituto de Inovação e investigação em Saúde, Universidade do Porto, Portugal.
authors.forename: M
authors.initials: M
authors.lastname: Silva
authors.affiliation: Departamento de Biologia Experimental, Faculdade de Medicina, Universidade do Porto, Portugal; I3S - Instituto de Inovação e investigação em Saúde, Universidade do Porto, Portugal.
authors.forename: D
authors.initials: D
authors.lastname: Martins
authors.affiliation: I3S - Instituto de Inovação e investigação em Saúde, Universidade do Porto, Portugal; Departmento de Doenças Renais, Urológicas e Infecciosas, Faculdade de Medicina, Universidade do Porto, Portugal.
authors.forename: A
authors.initials: A
authors.lastname: Charrua
authors.affiliation: Institute of Biomolecular Chemistry of the National Research Council (ICB-CNR), Naples, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Piscitelli
authors.affiliation: Departamento de Biologia Experimental, Faculdade de Medicina, Universidade do Porto, Portugal; I3S - Instituto de Inovação e investigação em Saúde, Universidade do Porto, Portugal. Electronic address: isatav@med.up.pt.
authors.forename: I
authors.initials: I
authors.lastname: Tavares
authors.affiliation: Departamento de Biologia Experimental, Faculdade de Medicina, Universidade do Porto, Portugal; I3S - Instituto de Inovação e investigação em Saúde, Universidade do Porto, Portugal.
authors.forename: C
authors.initials: C
authors.lastname: Morgado
authors.affiliation: Institute of Biomolecular Chemistry of the National Research Council (ICB-CNR), Naples, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Di Marzo
mesh_terms: D000577:Amides; D000581:Amidohydrolases / Q000378:metabolism*; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology; D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism; D002211:Capsaicin / Q000494:pharmacology; D059350:Chronic Pain / Q000188:drug therapy / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D003929:Diabetic Neuropathies / Q000188:drug therapy / Q000378:metabolism*; D063388:Endocannabinoids / Q000378:metabolism; D004983:Ethanolamines / Q000378:metabolism; D005557:Formaldehyde; D008297:Male; D008526:Medulla Oblongata / Q000378:metabolism*; D059226:Nociceptive Pain / Q000188:drug therapy / Q000378:metabolism*; D009829:Oleic Acids / Q000378:metabolism; D010169:Palmitic Acids / Q000378:metabolism; D053284:Polyunsaturated Alkamides / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017208:Rats, Wistar; D050916:TRPV Cation Channels / Q000819:agonists / Q000378:metabolism*; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D000577:Amides; D000581:Amidohydrolases; D018712:Analgesics, Non-Narcotic; D001095:Arachidonic Acids; D002211:Capsaicin; D063388:Endocannabinoids; D004983:Ethanolamines; D005557:Formaldehyde; D009829:Oleic Acids; D010169:Palmitic Acids; D053284:Polyunsaturated Alkamides; D012333:RNA, Messenger; D050916:TRPV Cation Channels; D000099252:Fatty Acid Amide Hydrolases; C493922:Trpv1 protein, rat; C488250:oleoylethanolamide; C005958:palmidrol; C078814:anandamide
keywords: Descending pain modulation; Diabetic neuropathic pain; FAAH; Periaqueductal grey; RVM; TRPV1