Methylglyoxal alters C-fibre Activity-Dependent Slowing and Induces Heat Hyperalgesia in a Sex-Dependent Manner
Velichkova, A. N.; Mutlu-Smith, M.; Hall, A. L.; Torsney, C.
Show abstract
IntroductionRaised plasma levels of the glycolytic metabolite methylglyoxal are associated with pain symptoms in patients with diabetic neuropathy. Methylglyoxal can regulate the function of NaV1.7 and NaV1.8 ion channels that are involved in the phenomenon of activity-dependent slowing (ADS) in C-fibre nociceptors. C-fibre ADS differs between the sexes and can regulate spinal network function. ObjectiveExplore the impact of methylglyoxal upon C-fibre ADS and pain sensitivity in both sexes. In addition, investigate the influence of ADS upon the processing of C-fibre inputs, in noxious heat responsive spinal neurons. ResultsCompound action potential recording of isolated dorsal roots incubated with methylglyoxal (100{micro}M, 3 hr) revealed a sex-dependent impact upon C-fibre ADS. In male roots, C-fibre ADS was reduced whereas in female roots it was increased. Acute methylglyoxal application (100{micro}M/1mM, 10 min) did not modify C-fibre ADS. Systemic methylglyoxal administration (5g, 3h prior) induced heat hyperalgesia in male but not female juvenile rats. Patch-clamp recording in spinal slices with attached dorsal roots revealed that length-dependent manipulation of ADS altered action potential firing to stimulus trains in noxious heat responsive Fos-EGFP+ spinal neurons. ConclusionWe propose that methylglyoxal sex-dependent regulation of C-fibre ADS influences the spinal processing of noxious heat inputs that may contribute to the male specific induction of heat hyperalgesia following systemic methylglyoxal treatment. SummaryMethylglyoxal, implicated in painful diabetic neuropathy, sex-dependently alters C-fibre ADS, potentially influencing spinal processing of noxious heat to drive heat hyperalgesia in males only.
Matching journals
The top 1 journal accounts for 50% of the predicted probability mass.
Similar papers in this journal
- Examination of the contribution of Nav1.7 to axonal propagation in nociceptors 96%
- Studies on CRMP2 SUMOylation-deficient transgenic mice identify sex-specific NaV1.7 regulation in the pathogenesis of chronic neuropathic pain 96%
- Microglial ablation does not affect opioid-induced hyperalgesia in rodents 95%
Similar papers in this journal
- Angiotensin II type 1 receptor activation facilitates pain hypersensitivity via dorsal horn pericyte mediated vasoconstriction 95%
- Truncated TrkB: The predominant TrkB Isoform in Nociceptors 95%
- De novo expression of neuropeptide Y in sensory neurons does not contribute to peripheral neuropathic pain 94%
Similar papers in this journal
- Functional NHE1 Expression is Critical to Blood Brain Barrier Integrity and Sumatriptan Blood to Brain Uptake 94%
- An objective approach to assess colonic pain in mice using colonometry 94%
- Differences in sensory nerve block between levobupivacaine and bupivacaine at low concentrations in humans and animals 94%
Similar papers in this journal
- ATP-Gated Potassium Channels Contribute to Ketogenic Diet-Mediated Analgesia in Mice. 95%
- FL/FLT3 signaling enhances mechanical pain hypersensitivity through Interleukin-1 beta (IL-1β) in male mice 94%
- Induction of long-term hyperexcitability by memory-related cAMP signaling in isolated nociceptor cell bodies 93%
Similar papers in this journal
- Spinal motoneurons respond aberrantly to serotonin in a rabbit model of cerebral palsy 93%
- Sensitisation of colonic nociceptors by TNFα is dependent on TNFR1 expression and p38 MAPK activity 93%
- Direct evidence for decreased presynaptic inhibition evoked by PBSt group I muscle afferents after chronic SCI and recovery with step-training in the decerebrated rat 93%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.