title: Medial plantar nerve ligation as a novel model of neuropathic pain in mice: pharmacological and molecular characterization.
abstract: Peripheral neuropathic pain is a consequence of an injury/disease of the peripheral nerves. The mechanisms involved in its pathophysiology are not entirely understood. To better understand the mechanisms involved in the development of peripheral nerve injury-induced neuropathic pain, more experimental models are required. Here, we developed a novel peripheral neuropathic pain model in mice by using a minimally invasive surgery and medial plantar nerve ligation (MPNL). After MPNL, mechanical allodynia was established, and mice quickly recovered from the surgery without any significant motor impairment. MPNL causes an increased expression of ATF-3 in the sensory neurons. At 14 days after surgery, gabapentin was capable of reversing the mechanical allodynia, whereas anti-inflammatory drugs and opioids were ineffective. MPNL-induced neuropathic pain was mediated by glial cells activation and the production of TNF-α and IL-6 in the spinal cord. These results indicate MPNL as a reasonable animal model for the study of peripheral neuropathic pain, presenting analgesic pharmacological predictivity to clinically used drugs. The results also showed molecular phenotypic changes similar to other peripheral neuropathic pain models, with the advantage of a lack of motor impairment. These features indicate that MPNL might be more appropriate for the study of neuropathic pain than classical models.
authors.affiliation: Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Brazil.
authors.forename: Morena B
authors.initials: MB
authors.lastname: Sant'Anna
authors.affiliation: Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Brazil.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Kusuda
authors.affiliation: Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Brazil.
authors.forename: Tiago A
authors.initials: TA
authors.lastname: Bozzo
authors.affiliation: Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Brazil.|Graduation Program in Basic and Apply Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Gabriel S
authors.initials: GS
authors.lastname: Bassi
authors.affiliation: Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Brazil.
authors.forename: José C
authors.initials: JC
authors.lastname: Alves-Filho
authors.affiliation: Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Brazil.
authors.forename: Fernando Q
authors.initials: FQ
authors.lastname: Cunha
authors.affiliation: Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Brazil.
authors.forename: Sergio H
authors.initials: SH
authors.lastname: Ferreira
authors.affiliation: Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Brazil.
authors.forename: Guilherme R
authors.initials: GR
authors.lastname: Souza
authors.affiliation: Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Brazil.
authors.forename: Thiago M
authors.initials: TM
authors.lastname: Cunha
mesh_terms: D051700:Activating Transcription Factor 3 / Q000235:genetics / Q000378:metabolism; D000588:Amines / Q000494:pharmacology; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology; D004195:Disease Models, Animal; D000077206:Gabapentin; D005786:Gene Expression Regulation; D006801:Humans; D006930:Hyperalgesia / Q000378:metabolism / Q000503:physiopathology* / Q000517:prevention & control; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008026:Ligation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000502:physiology*; D009437:Neuralgia / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D013979:Tibial Nerve / Q000187:drug effects / Q000293:injuries / Q000378:metabolism / Q000503:physiopathology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
chemical_list: D051700:Activating Transcription Factor 3; D000588:Amines; D000700:Analgesics; C103002:Atf3 protein, mouse; D003509:Cyclohexanecarboxylic Acids; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; C577686:interleukin-6, mouse; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin