title: The importance of TRPV1-sensitisation factors for the development of neuropathic pain.
abstract: Transient receptor potential vanilloid type 1 (TRPV1), classically associated with transduction of high-temperature and low-pH pain, underlies pain hypersensitivity in neuropathic pain. The molecular regulation of TRPV1 channel activity is not yet fully understood. Therefore, we investigated factors regulating sensitisation of this receptor during development of neuropathic pain in a rat model of chronic construction injury (CCI) in the dorsal root ganglia (DRG). In the rat CCI model, elevated levels of pro-inflammatory cytokines (TNFα, IL-1β and IL-6) in DRG corresponded to development of neuropathic pain. We assessed the expression of known kinases influencing TRPV1 sensitisation at the mRNA and/or protein level. Protein kinase C ε (PKCε) showed the strongest upregulation at the mRNA and protein levels among all tested kinases. Co-expression of PKCε and TRPV1 in L5 DRG of CCI animals was high during the development of neuropathic pain. The number of neurons expressing PKCε increased throughout the experiment. We provide complex data on the expression of a variety of factors involved in TRPV1 sensitisation in a CCI model of neuropathic pain. Our study supports evidence for involvement of TRPV1 in the development of neuropathic pain, by showing increased expression of interleukins and kinases responsible for the channel sensitisation. TNFα and NGF seem to play a role in the transition from acute to neuropathic pain, while PKCε in its maintenance. Further studies might confirm their significance as novel targets for the treatment of neuropathic pain.
authors: Laboratory of Pain Pathophysiology, Department of Pain Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Smetna 12 Street, 31-343 Krakow, Poland. Electronic address: n.malek@if-pan.krakow.pl.
authors: Natalia
authors: N
authors: Malek
authors: Laboratory of Pain Pathophysiology, Department of Pain Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Smetna 12 Street, 31-343 Krakow, Poland. Electronic address: pajak@if-pan.krakow.pl.
authors: Agnieszka
authors: A
authors: Pajak
authors: Laboratory of Pain Pathophysiology, Department of Pain Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Smetna 12 Street, 31-343 Krakow, Poland. Electronic address: natkol@if-pan.krakow.pl.
authors: Natalia
authors: N
authors: Kolosowska
authors: Laboratory of Pain Pathophysiology, Department of Pain Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Smetna 12 Street, 31-343 Krakow, Poland. Electronic address: mateusz.kucharczyk@uj-edu.pl.
authors: Mateusz
authors: M
authors: Kucharczyk
authors: Laboratory of Pain Pathophysiology, Department of Pain Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Smetna 12 Street, 31-343 Krakow, Poland. Electronic address: starow@if-pan.krakow.pl.
authors: Katarzyna
authors: K
authors: Starowicz
mesh_terms: D000818:Animals; D005727:Ganglia, Spinal / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008297:Male; D009437:Neuralgia / Q000378:metabolism*; D051744:Protein Kinase C-epsilon / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D050916:TRPV Cation Channels / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D053583:Interleukin-1beta; D015850:Interleukin-6; D012333:RNA, Messenger; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; D014409:Tumor Necrosis Factor-alpha; D051744:Protein Kinase C-epsilon
keywords: CCI; DRG; Neuronal inflammation; Neuropathic pain; TRPV1 sensitisation