title: Lesion of the dopaminergic nigrostriatal pathway induces trigeminal dynamic mechanical allodynia.
abstract: BACKGROUND
  Pain constitutes the major non motor syndrome in Parkinson's disease (PD) and includes neuropathic pain; however current drug therapies used to alleviate it have only limited efficacy. This is probably due to poor understanding of the mechanisms underlying it.
  
  
  OBJECTIVE
  We investigated a major class of trigeminal neuropathic pain, dynamic mechanical allodynia (DMA), in a rat model of PD and in which a bilateral 6-hydroxy dopamine (6-OHDA) injection was administered to produce a lesion of the nigrostriatal dopaminergic pathway.
  
  
  CONCLUSIONS
  Lesioned animals presented significant DMA in the orofacial area that occurred from 4 days to 5 weeks post-injury. To investigate a segmental implication in the neuropathic pain induced by dopamine depletion, the expression of the isoform gamma of the protein kinase C (PKCg) and phosphorylated extracellular signal-regulated kinases 1/2 (pERK1/2) was explored in the medullary dorsal horn (MDH). There was a high increase in PKCg expression in the III and IIi laminae of the MDH of lesioned-animals compared to shams. pERK1/2 expression was also significantly high in the ipsilateral MDH of lesioned rats in response to non-noxious tactile stimulus of the orofacial region. Since pERK1/2 is expressed only in response to nociceptive stimuli in the dorsal spinal horn, the current study demonstrates that non-noxious stimuli evoke allodynic response. Intraperitoneal and intracisternal administrations of bromocriptine, a dopamine 2 receptor (D2R) agonist, significantly decreased DMA compared to control rats injected with saline. These data demonstrate for the first time that nigrostriatal dopaminergic depletion produces trigeminal neuropathic pain that at least involves a segmental mechanism. In addition, bromocriptine was shown to have a remarkable analgesic effect on this neuropathic pain symptom.
authors.affiliation: Laboratoire de neuro-psychopharmacology des systèmes dopaminergiques sous corticaux, Clermont Université, Université d'Auvergne Clermont-Ferrand, EA7280, France.
authors.forename: Wisam
authors.initials: W
authors.lastname: Dieb
authors.affiliation: Laboratoire de neuro-psychopharmacology des systèmes dopaminergiques sous corticaux, Clermont Université, Université d'Auvergne Clermont-Ferrand, EA7280, France.
authors.forename: Omar
authors.initials: O
authors.lastname: Ouachikh
authors.affiliation: Laboratoire de neuro-psychopharmacology des systèmes dopaminergiques sous corticaux, Clermont Université, Université d'Auvergne Clermont-Ferrand, EA7280, France ; Service de Neurologie, CHU Clermont-Ferrand Clermont-Ferrand, 63000, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Durif
authors.affiliation: Laboratoire de neuro-psychopharmacology des systèmes dopaminergiques sous corticaux, Clermont Université, Université d'Auvergne Clermont-Ferrand, EA7280, France.
authors.forename: Aziz
authors.initials: A
authors.lastname: Hafidi
mesh_terms: D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons / Q000187:drug effects* / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006930:Hyperalgesia / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D016627:Oxidopamine; D010147:Pain Measurement; D010302:Parkinson Disease, Secondary / Q000378:metabolism / Q000503:physiopathology*; D010766:Phosphorylation; D010812:Physical Stimulation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D014277:Trigeminal Neuralgia / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology
chemical_list: D016627:Oxidopamine; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Atypical facial algia; Parkinson disease; basal ganglia; burning mouth syndrome; orofacial pain; trigeminal subnucleus caudalis (Sp5C)