title: The lesion of dorsolateral funiculus changes the antiallodynic effect of the intrathecal muscimol and baclofen in distinct phases of neuropathic pain induced by spinal nerve ligation in rats.
abstract: The abnormal firing of damaged primary afferents and the changes in the central nervous system (CNS) play important role in the initiation and maintenance phases of neuropathic pain. These phases of neuropathic pain involve changes in the GABAergic control of descending pathways that travel through the dorsolateral funiculus (DLF). The present study shows that unilateral DLF lesion increased the antiallodynic effect of muscimol (0.2μg/5μL) (a GABAA receptor agonist) in the initiation, but not maintenance phase of the mechanical allodynia induced by a spinal nerve ligation (SNL) of the ipsilateral hindpaw of rats. The unilateral DLF lesion increased the antiallodynic effect of baclofen (0.8μg/5μL) (a GABAB receptor agonist) in the initiation phase and reduced your effect in the maintenance phase of the mechanical allodynia induced by a spinal nerve ligation (SNL) of the ipsilateral paw of rats. The unilateral DLF lesion significantly reduced the proallodynic effect of an intrathecal injection of phaclofen (30μg/5μL) (a GABAB receptor antagonist), but not bicuculline (0.3μg/5μL) (a GABAA receptor antagonist). The effect of DLF lesion on the proallodynic effect of phaclofen was observed in the maintenance, but not in the initiation phase of the mechanical allodynia induced by SNL. We than conclude that the spinal GABAergic neurotransmission is negatively modulated by DLF using GABAA and GABAB receptors, in the initiation phase of mechanical allodynia induced by SNL. In addition, the integrity of DLF is necessary for the effectiveness of GABAergic transmission that occurs via spinal GABAB, but not GABAA receptors, in the maintenance phase of mechanical allodynia induced by SNL.
authors.affiliation: Oswaldo Cruz Foundation (FIOCRUZ), Porto Velho, Rondônia, Brazil.
authors.forename: Quintino Moura
authors.initials: QM
authors.lastname: Dias
authors.affiliation: Department of Pharmacology, Ribeirao Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil. Electronic address: wadprado@fmrp.usp.br.
authors.forename: Wiliam A
authors.initials: WA
authors.lastname: Prado
mesh_terms: D000818:Animals; D001418:Baclofen / Q000008:administration & dosage / Q000031:analogs & derivatives*; D001640:Bicuculline / Q000008:administration & dosage; D007839:Functional Laterality; D018682:GABA Agents / Q000008:administration & dosage*; D006930:Hyperalgesia / Q000188:drug therapy / Q000209:etiology; D007278:Injections, Spinal; D008026:Ligation / Q000009:adverse effects; D008297:Male; D009118:Muscimol / Q000008:administration & dosage*; D009437:Neuralgia / Q000150:complications / Q000188:drug therapy / Q000209:etiology; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects; D010812:Physical Stimulation; D051381:Rats; D017208:Rats, Wistar; D066148:Spinal Cord Dorsal Horn / Q000187:drug effects / Q000473:pathology*; D013127:Spinal Nerves / Q000293:injuries*; D018709:Statistics, Nonparametric
chemical_list: D018682:GABA Agents; C052329:phaclofen; D009118:Muscimol; D001418:Baclofen; D001640:Bicuculline
keywords: Allodynia; Descending facilitatory mechanisms; Dorsolateral funiculus lesion; Neuropathic pain; Spinal GABAergic modulation