title: Nerve regenerative effects of GABA-B ligands in a model of neuropathic pain.
abstract: Neuropathic pain arises as a direct consequence of a lesion or disease affecting the peripheral somatosensory system. It may be associated with allodynia and increased pain sensitivity. Few studies correlated neuropathic pain with nerve morphology and myelin proteins expression. Our aim was to test if neuropathic pain is related to nerve degeneration, speculating whether the modulation of peripheral GABA-B receptors may promote nerve regeneration and decrease neuropathic pain. We used the partial sciatic ligation- (PSL-) induced neuropathic model. The biochemical, morphological, and behavioural outcomes of sciatic nerve were analysed following GABA-B ligands treatments. Simultaneous 7-days coadministration of baclofen (10 mg/kg) and CGP56433 (3 mg/kg) alters tactile hypersensitivity. Concomitantly, specific changes of peripheral nerve morphology, nerve structure, and myelin proteins (P0 and PMP22) expression were observed. Nerve macrophage recruitment decreased and step coordination was improved. The PSL-induced changes in nociception correlate with altered nerve morphology and myelin protein expression. Peripheral synergic effects, via GABA-B receptor activation, promote nerve regeneration and likely ameliorate neuropathic pain.
authors.affiliation: Dip. Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Via G. Balzaretti 9, 20133 Milan, Italy.
authors.forename: Valerio
authors.identifier: 0000-0002-6903-7042
authors.initials: V
authors.lastname: Magnaghi
authors.affiliation: Dip. Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Via G. Balzaretti 9, 20133 Milan, Italy.
authors.forename: Luca Franco
authors.identifier: 0000-0003-4784-1221
authors.initials: LF
authors.lastname: Castelnovo
authors.affiliation: Blond McIndoe Laboratories, Institute of Inflammation and Repair, Faculty of Life Science, The University of Manchester, 3.107 Stopford Building, Manchester M13 9PT, UK.
authors.forename: Alessandro
authors.identifier: 0000-0003-4435-6423
authors.initials: A
authors.lastname: Faroni
authors.affiliation: Hand Surgery Department, St. Joseph MultiMedica Hospital of Milan, Via San Vittore 12, 20123 Milan, Italy.
authors.forename: Erica
authors.initials: E
authors.lastname: Cavalli
authors.affiliation: Dip. Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Via G. Balzaretti 9, 20133 Milan, Italy.
authors.forename: Lucia
authors.identifier: 0000-0001-8045-3146
authors.initials: L
authors.lastname: Caffino
authors.affiliation: Dip. Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Via G. Balzaretti 9, 20133 Milan, Italy.
authors.forename: Alessandra
authors.identifier: 0000-0001-6281-514X
authors.initials: A
authors.lastname: Colciago
authors.affiliation: Dip. Scienze Biomediche per la Salute, Università degli Studi di Milano, Via L. Mangiagalli 31, 20133 Milan, Italy.
authors.forename: Patrizia
authors.identifier: 0000-0003-4726-2115
authors.initials: P
authors.lastname: Procacci
authors.affiliation: Hand Surgery Department, St. Joseph MultiMedica Hospital of Milan, Via San Vittore 12, 20123 Milan, Italy ; Dip. Scienze Cliniche e di Comunità, Plastic Surgery School, Università degli Studi di Milano, Via San Barnaba 22, 20122 Milan, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Pajardi
mesh_terms: D000818:Animals; D001418:Baclofen / Q000008:administration & dosage; D015870:Gene Expression; D006801:Humans; D006930:Hyperalgesia / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D008024:Ligands; D009185:Myelin Proteins / Q000096:biosynthesis; D009186:Myelin Sheath / Q000235:genetics / Q000378:metabolism; D009416:Nerve Regeneration; D009437:Neuralgia / Q000188:drug therapy* / Q000503:physiopathology; D051381:Rats; D012584:Sciatic Nerve / Q000378:metabolism / Q000503:physiopathology; D020426:Sciatic Neuropathy / Q000188:drug therapy* / Q000503:physiopathology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D008024:Ligands; D009185:Myelin Proteins; C489546:Pmp22 protein, rat; D005680:gamma-Aminobutyric Acid; D001418:Baclofen