TAFA4, a Chemokine-like Protein, Modulates Injury-Induced Mechanical and Chemical Pain Hypersensitivity in Mice

Delfini, Marie-Claire; Mantilleri, Annabelle; Gaillard, Stéphane; Hao, Jizhe; Reynders, Ana; Malapert, Pascale; Alonso, Serge; François, Amaury; Barrère, Christian; Seal, Rebecca P.; Landry, Marc; Eschallier, Alain; Alloui, Abdelkrim; Bourinet, Emmanuel; Delmas, Patrick; Feuvre, Yves Le; Moqrich, Aziz

doi:10.1016/j.celrep.2013.09.013

Cited by 130 publications

(164 citation statements)

References 30 publications

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“…The fact that the presynaptic cell in the pairs consistently showed lower thresholds and slower dorsal root evoked excitatory post synaptic potentials (EPSPs) than the postsynaptic neuron was consistent with the notion that the dorsal root excitation was associated with relatively large diameter rapidly conducting C-LTMs while the postsynaptic cell was in receipt of c-nociceptive inputs (Lu and Perl, 2003). Further support for the notion that C-LTM inputs can supress nociceptive impulses comes from the observation that administration of TAFA4, a chemokine protein and specific marker on C-LTMs, reduced inflammation induced mechanical hypersensitivity (Delfini et al, 2013). In contrast, TAFA4 knockout mice displayed enhanced mechanical hypersensitivity following inflammation or injury which could be reversed by administration of TAFA4 protein into the spinal cord (Delfini et al, 2013).…”

Section: C-tactile Afferents Inhibit Painsupporting

confidence: 68%

“…Further support for the notion that C-LTM inputs can supress nociceptive impulses comes from the observation that administration of TAFA4, a chemokine protein and specific marker on C-LTMs, reduced inflammation induced mechanical hypersensitivity (Delfini et al, 2013). In contrast, TAFA4 knockout mice displayed enhanced mechanical hypersensitivity following inflammation or injury which could be reversed by administration of TAFA4 protein into the spinal cord (Delfini et al, 2013). Taken together these findings are consistent with an analgesic role for C-LTMs via their modulation of nociceptive inputs to the spinal cord.…”

Section: C-tactile Afferents Inhibit Painmentioning

confidence: 99%

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C-tactile afferents: Cutaneous mediators of oxytocin release during affiliative tactile interactions?

et al. 2017

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Low intensity, non-noxious, stimulation of cutaneous somatosensory nerves has been shown to trigger oxytocin release and is associated with increased social motivation, plus reduced physiological and behavioural reactivity to stressors. However, to date, little attention has been paid to the specific nature of the mechanosensory nerves which mediate these effects. In recent years, the neuroscientific study of human skin nerves (microneurography studies on single peripheral nerve fibres) has led to the identification and characterisation of a class of touch sensitive nerve fibres named C-Tactile afferents. Neither itch nor pain receptive, these unmyelinated, low threshold mechanoreceptors, found only in hairy skin, respond optimally to low force/velocity stroking touch. Notably, the speed of stroking which c-tactile afferents fire most strongly to is also that which people perceive to be most pleasant. The social touch hypothesis posits that this system of nerves has evolved in mammals to signal the rewarding value of physical contact in nurturing and social interactions. In support of this hypothesis, in this paper we review the evidence that cutaneous stimulation directly targeted to optimally activate c-tactile afferents reduces physiological arousal, carries a positive affective value and, under healthy conditions, inhibits responses to painful stimuli. These effects mirror those, we also review, which have been reported following endogenous release and exogenous administration of oxytocin. Taken together this evidence suggests c-tactile afferent stimulation may mediate oxytocin release during affiliative tactile interactions.

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Section: C-tactile Afferents Inhibit Painsupporting

confidence: 68%

Section: C-tactile Afferents Inhibit Painmentioning

confidence: 99%

C-tactile afferents: Cutaneous mediators of oxytocin release during affiliative tactile interactions?

et al. 2017

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“…This higher variability, as compared to nociceptive C-fibres, was unexpected, as we hypothesised that VGluT3 + fibres would be a more homogenous group than the large populations of peptidergic and non-peptidergic C-fibres that were electrically stimulated in VGluT3 −/− mice. However, a recent study also reported heterogeneous responses in putative C-LTMRs upon application of hypo-osmotic solution or a TRPA1-receptor agonist [12]. The response variability observed by us and others may reflect functional heterogeneity or the existence of further not yet identified subpopulations of VGluT3 + A- and C-fibres.…”

Section: Discussionmentioning

confidence: 57%

Presynaptic inhibition of optogenetically identified VGluT3+ sensory fibres by opioids and baclofen

Honsek

Seal

Sandkühler

2015

Pain

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Distinct subsets of sensory nerve fibres are involved in mediating mechanical and thermal pain hypersensitivity. They may also differentially respond to analgesics. Heat-sensitive C-fibres, for example, are thought to respond to µ-opioid receptor (MOR) activation while mechanoreceptive fibres are supposedly sensitive to δ-opioid receptor (DOR) or GABAB receptor (GABABR) activation. The suggested differential distribution of inhibitory neurotransmitter receptors on different subsets of sensory fibres is, however, heavily debated. We now quantitatively compared the degree of presynaptic inhibition exerted by opioids and the GABABR agonist baclofen on 1) vesicular glutamate transporter subtype 3 positive (VGluT3+) non-nociceptive primary afferent fibres and 2) putative nociceptive C-fibres. To investigate VGluT3+ sensory fibres, we evoked excitatory postsynaptic currents with blue light at the level of the dorsal root ganglion (DRG) in spinal cord slices of mice, expressing channelrhodopsin-2. Putative nociceptive C-fibres were explored in VGluT3-knockout mice via electrical stimulation. The MOR agonist DAMGO strongly inhibited both VGluT3+ and VGluT3− C-fibres innervating lamina I neurons but generally had less influence on fibres innervating lamina II neurons. The DOR agonist SNC80 did not have any pronounced effect on synaptic transmission in any fibre type tested. Baclofen, in striking contrast, powerfully inhibited all fibre populations investigated. In summary, we report optogenetic stimulation of DRG neurons in spinal slices as capable approach for the subtype-selective investigation of primary afferent nerve fibres. Overall, the pharmacological accessibility of different subtypes of sensory fibres considerably overlaps, indicating that MOR, DOR and GABABR expression is not substantially segregated between heat and mechanosensitive fibres.

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“…In conclusion, our work identifies FAM19A4 as a novel cytokine ligand of FPR1 in macrophages for the first time. However, Delfini et al 38 have defined FAM19A4 to be a specific marker of the C-low-threshold mechanoreceptor, which could be a potent analgesic in pain relief. FPR1 is not restricted to leukocytes involved in inflammatory responses toward infection, but is also found on the cells of the neuromuscular and endocrine system.…”

Section: Fpr1 Is a Functional Receptor Of Fam19a4mentioning

confidence: 99%

FAM19A4 is a novel cytokine ligand of formyl peptide receptor 1 (FPR1) and is able to promote the migration and phagocytosis of macrophages

Wang

et al. 2014

Cell Mol Immunol

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FAM19A4 is an abbreviation for family with sequence similarity 19 (chemokine (C-C motif)-like) member A4, which is a secretory protein expressed in low levels in normal tissues. The biological functions of FAM19A4 remain to be determined, and its potential receptor(s) is unclarified. In this study, we demonstrated that FAM19A4 was a classical secretory protein and we verified for the first time that its mature protein is composed of 95 amino acids. We found that the expression of this novel cytokine was upregulated in lipopolysaccharide (LPS)-stimulated monocytes and macrophages and was typically in polarized M1. FAM19A4 shows chemotactic activities on macrophages and enhances the macrophage phagocytosis of zymosan both in vitro and in vivo with noticeable increases of the phosphorylation of protein kinase B (Akt). FAM19A4 can also increase the release of reactive oxygen species (ROS) upon zymosan stimulation. Furthermore, based on receptor internalization, radio ligand binding assays and receptor blockage, we demonstrated for the first time that FAM19A4 is a novel ligand of formyl peptide receptor 1 (FPR1). The above data indicate that upon inflammatory stimulation, monocyte/macrophage-derived FAM19A4 may play a crucial role in the migration and activation of macrophages during pathogenic infections.

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TAFA4, a Chemokine-like Protein, Modulates Injury-Induced Mechanical and Chemical Pain Hypersensitivity in Mice

Cited by 130 publications

References 30 publications

C-tactile afferents: Cutaneous mediators of oxytocin release during affiliative tactile interactions?

C-tactile afferents: Cutaneous mediators of oxytocin release during affiliative tactile interactions?

Presynaptic inhibition of optogenetically identified VGluT3+ sensory fibres by opioids and baclofen

FAM19A4 is a novel cytokine ligand of formyl peptide receptor 1 (FPR1) and is able to promote the migration and phagocytosis of macrophages

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