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1.  Mechanical allodynia 
Pflugers Archiv  2014;467:133-139.
Mechanical allodynia (other pain) is a painful sensation caused by innocuous stimuli like light touch. Unlike inflammatory hyperalgesia that has a protective role, allodynia has no obvious biological utility. Allodynia is associated with nerve damage in conditions such as diabetes, and is likely to become an increasing clinical problem. Unfortunately, the mechanistic basis of this enhanced sensitivity is incompletely understood. In this review, we describe evidence for the involvement of candidate mechanosensitive channels such as Piezo2 and their role in allodynia, as well as the peripheral and central nervous system mechanisms that have also been implicated in this form of pain. Specific treatments that block allodynia could be very useful if the cell and molecular basis of the condition could be determined. There are many potential mechanisms underlying this condition ranging from alterations in mechanotransduction and sensory neuron excitability to the actions of inflammatory mediators and wiring changes in the CNS. As with other pain conditions, it is likely that the range of redundant mechanisms that cause allodynia will make therapeutic intervention problematic.
doi:10.1007/s00424-014-1532-0
PMCID: PMC4281368  PMID: 24846747
Mechanical allodynia; Mechanotransduction; Piezo2; cAMP; Neuropathic pain
2.  Nav1.9 Channel Contributes to Mechanical and Heat Pain Hypersensitivity Induced by Subacute and Chronic Inflammation 
PLoS ONE  2011;6(8):e23083.
Inflammation is known to be responsible for the sensitization of peripheral sensory neurons, leading to spontaneous pain and invalidating pain hypersensitivity. Given its role in regulating neuronal excitability, the voltage-gated Nav1.9 channel is a potential target for the treatment of pathological pain, but its implication in inflammatory pain is yet not fully described. In the present study, we examined the role of the Nav1.9 channel in acute, subacute and chronic inflammatory pain using Nav1.9-null mice and Nav1.9 knock-down rats. In mice we found that, although the Nav1.9 channel does not contribute to basal pain thresholds, it plays an important role in heat pain hypersensitivity induced by subacute paw inflammation (intraplantar carrageenan) and chronic ankle inflammation (complete Freund's adjuvant-induced monoarthritis). We showed for the first time that Nav1.9 also contributes to mechanical hypersensitivity in both models, as assessed using von Frey and dynamic weight bearing tests. Consistently, antisense-based Nav1.9 gene silencing in rats reduced carrageenan-induced heat and mechanical pain hypersensitivity. While no changes in Nav1.9 mRNA levels were detected in dorsal root ganglia (DRGs) during subacute and chronic inflammation, a significant increase in Nav1.9 immunoreactivity was observed in ipsilateral DRGs 24 hours following carrageenan injection. This was correlated with an increase in Nav1.9 immunolabeling in nerve fibers surrounding the inflamed area. No change in Nav1.9 current density could be detected in the soma of retrolabeled DRG neurons innervating inflamed tissues, suggesting that newly produced channels may be non-functional at this level and rather contribute to the observed increase in axonal transport. Our results provide evidence that Nav1.9 plays a crucial role in the generation of heat and mechanical pain hypersensitivity, both in subacute and chronic inflammatory pain models, and bring new elements for the understanding of its regulation in those models.
doi:10.1371/journal.pone.0023083
PMCID: PMC3155549  PMID: 21857998
3.  Botulinum toxin‐a treatment reduces human mechanical pain sensitivity and mechanotransduction 
Annals of Neurology  2014;75(4):591-596.
The mechanisms underlying the analgesic effects of botulinum toxin serotype A (BoNT‐A) are not well understood. We have tested the hypothesis that BoNT‐A can block nociceptor transduction. Intradermal administration of BoNT‐A to healthy volunteers produced a marked and specific decrease in noxious mechanical pain sensitivity, whereas sensitivity to low‐threshold mechanical and thermal stimuli was unchanged. BoNT‐A did not affect cutaneous innervation. In cultured rodent primary sensory neurons, BoNT‐A decreased the proportion of neurons expressing slowly adapting mechanically gated currents linked to mechanical pain transduction. Inhibition of mechanotransduction provides a novel locus of action of BoNT‐A, further understanding of which may extend its use as an analgesic agent. Ann Neurol 2014;75:591–596
doi:10.1002/ana.24122
PMCID: PMC4112716  PMID: 24550077

Results 1-3 (3)