Biology subjects

O'Flaherty, R.

Publications and source records attributed to O'Flaherty, R..

3 recordsLinked to original sources

bioRxiv2024

The impact of sex differences on perceived pain intensity in pain protocol standardization

BackgroundSex differences have been widely demonstrated in both acute and chronic pain. Sex differences may have wider impact on research design and analysis than already established. This study addresses an important methodological aspect with regards to how sex differences could influence the design of standardized experimental pain protocols used to characterize an individuals pain response. MethodsThis study addresses sex differences of perceived pain at tonic heat pain threshold (HPT). Participants used a computerized visual analogue scale (CoVAS) to continually rated subjective pain intensity during tonic HPT. Metrics (Mean, Standard Deviation, Maximum) were extracted from the CoVAS to characterize perceived pain. ResultsFemale participants rated pain intensity at HPT significantly lower than male participants across all extracted metrics used to characterize the coVAS rating. The effect of sex on the mean and standard deviation of pain intensity ratings at HPT was medium, while the effect size of sex on the maximum pain intensity rating at HPT was large. ConclusionThe significant sex differences in perceived pain intensity at HPT indicates that methods of standardization to a specific pain intensity merit sex-specific consideration. Additionally, these observed sex differences underscore the necessity for sex specific design across both pre-clinical and clinical studies of pain.

neuroscience↗

bioRxiv2024

Differential effects of conventional transcranial direct current stimulation (tDCS) and high-definition transcranial direct current stimulation (HD-tDCS) of the cerebellum on offset analgesia

BackgroundOffset analgesia (OA) describes the large decrease in perceived pain in response to a minor decrease in applied painful thermal stimulus. Here non-invasive brain stimulation (NIBS) is used to modulate the cerebellum, since the cerebellum is known to signal sensory prediction errors and is implicated in pain processing. MethodsAn OA protocol individualized to heat pain threshold (HPT) was applied via TSA-II (Medoc, Israel). NIBS interventions were applied prior to OA. Cathodal cerebellar transcranial direct current stimulation (tDCS) and high-definition (4X1) transcranial direct current stimulation (HD-tDCS) were applied to 46 healthy participants within a sham controlled repeated measures design to examine whether diffuse or focal stimulation differentially modulates OA. ResultsOA induced hypoalgesia was robust, with 90% of responses showing a drop in perceived pain ({delta}VAS) > 10 following the 1{degrees}C fall in temperature. This OA response was augmented following a protocol with sham and focal cathodal cerebellar stimulation on four OA parameters (OA latency, VAS minimum, VAS mean and VAS 2nd max) relative to pre-stimulation. This effect was differential to the protocol with sham and conventional tDCS where two OA metrics altered (OA duration, VAS 2nd max). ConclusionOA enhancement via cathodal cerebellar NIBS may involve both a placebo effect and sustaining a noxious sensory prediction error. Understanding how the cerebellum is involved in OA could enhance therapies for pain patients.

neuroscience↗

bioRxiv2024

Unravelling the glycome in human intervertebral disc degeneration: Aberrant glycosylation modulates inflammation and metabolism.

Intervertebral disc (IVD) degeneration is one of the major contributing causes of low back pain (LBP), a common health issue that imposes a significant socio-economic burden on society. Previous work has demonstrated a dysregulated glycome in animal models of IVD degeneration; however, the role of glycosylation in pathogenesis is unknown. The objective of this study was to characterise altered glycan expression in IVD degeneration and elucidate the functional role of this response. Glycans in human healthy (n=6) and degenerated IVD (n=6) were examined through UPLC-MS and MALDI-IMS. These findings were correlated with proteomic analysis by LC-MS and functional in vitro studies using RNA sequencing. IVD degeneration was associated with a hypersialylated N-glycome, predominantly -2,6 linked sialic acid. Confirming hypersialylation, we investigated sialylations functional role through mechanistic studies using a sialylation inhibitor (3Fax-peracetyl Neu5Ac). Sialylation inhibition in vitro modulated inflammatory and metabolic pathways, demonstrating a functional role for glycosylation in IVD degeneration. Brief summaryIVD degeneration is associated with altered glycosylation, a potential target for new therapies.

bioengineering↗