title: Peripheral inflammatory pain sensitisation is independent of mast cell activation in male mice.
abstract: The immune and sensory systems are known for their close proximity and interaction. Indeed, in a variety of pain states, a myriad of different immune cells are activated and recruited, playing a key role in neuronal sensitisation. During inflammatory pain it is thought that mast cells (MC) are one of the immune cell types involved in this process, but so far the evidence outlining their direct effect on neuronal cells remains unclear. To clarify whether MC are involved in inflammatory pain states, we used a transgenic mouse line (Mctp5Cre-iDTR) in which MC could be depleted in an inducible manner by administration of diphtheria toxin. Our results show that ablation of MC in male mice did not result in any change in mechanical and thermal hypersensitivity in the CFA model of inflammatory pain. Similarly, edema and temperature triggered by CFA inflammation at the injection site remained identical in MC depleted mice compared with their littermate controls. In addition, we show that Mctp5Cre-iDTR mice display normal levels of mechanical hypersensitivity after local injection of nerve growth factor (NGF), a factor well characterised to produce peripheral sensitisation and for being upregulated upon injury and inflammation. We also demonstrate that NGF treatment in vitro does not lead to an increased level of tumor necrosis factor-α in bone marrow-derived MC. Furthermore, our qRT-PCR data reveal that MC express negligible levels of NGF receptors, thereby explaining the lack of response to NGF. Together, our data suggest that MC do not play a direct role in peripheral sensitisation during inflammatory conditions.
authors.affiliation: Wolfson Centre for Age-Related Diseases, King's College London, United Kingdom.
authors.forename: Douglas M
authors.initials: DM
authors.lastname: Lopes
authors.forename: Franziska
authors.initials: F
authors.lastname: Denk
authors.forename: Kim I
authors.initials: KI
authors.lastname: Chisholm
authors.forename: Tesha
authors.initials: T
authors.lastname: Suddason
authors.forename: Camille
authors.initials: C
authors.lastname: Durrieux
authors.forename: Matthew
authors.initials: M
authors.lastname: Thakur
authors.forename: Clive
authors.initials: C
authors.lastname: Gentry
authors.forename: Stephen B
authors.initials: SB
authors.lastname: McMahon
mesh_terms: D000818:Animals; D006930:Hyperalgesia / Q000276:immunology*; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D020932:Nerve Growth Factor / Q000494:pharmacology; D010146:Pain / Q000276:immunology* / Q000378:metabolism; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D014409:Tumor Necrosis Factor-alpha; D020932:Nerve Growth Factor