Endovanilloid control of pain modulation by the rostroventromedial medulla in an animal model of diabetic neuropathy

• Published in: Neuropharmacology 2016-08, Vol.107, p.49-57
• Main Authors: Silva, M., Martins, D., Charrua, A., Piscitelli, F., Tavares, I., Morgado, C., Di Marzo, V.
• Format: Article
• Language: English
• Subjects: Amidohydrolases - metabolism; Analgesics, Non-Narcotic - pharmacology; Animals; Arachidonic Acids - metabolism; Capsaicin - pharmacology; Chronic Pain - drug therapy; Chronic Pain - metabolism; Descending pain modulation; Diabetes Mellitus, Experimental - metabolism; Diabetic neuropathic pain; Diabetic Neuropathies - drug therapy; Diabetic Neuropathies - metabolism; Endocannabinoids - metabolism; Ethanolamines - metabolism; FAAH; Formaldehyde; Male; Medulla Oblongata - metabolism; Nociceptive Pain - drug therapy; Nociceptive Pain - metabolism; Oleic Acids - metabolism; Palmitic Acids - metabolism; Periaqueductal grey; Polyunsaturated Alkamides - metabolism; Rats, Wistar; RNA, Messenger - metabolism; RVM; TRPV Cation Channels - agonists; TRPV Cation Channels - metabolism; TRPV1
• ISSN: 0028-3908; 1873-7064
• DOI: 10.1016/j.neuropharm.2016.03.007

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. •The expression on TRPV1 mRNA is upregulated in the RVM of diabetic rats.•Endovanilloid levels are increased in the RVM of diabetic rats whereas the opposite occurs in FAAH expression.•TRPV1 potentiates RVM-mediated anti-hyperalgesia during diabetic neuropathy.