Biology subjects

Finn, D. P.

Publications and source records attributed to Finn, D. P..

5 recordsLinked to original sources

bioRxiv2026

Sex-dependent endocannabinoid adaptations in supraspinal pain modulatory circuits after peripheral nerve injury

Peripheral nerve injury produces persistent pain-related behaviours that differ between sexes, but whether chronic neuropathic pain is accompanied by sex-dependent alterations in endocannabinoid signalling across pain-modulatory circuits remains unclear. We quantified endocannabinoids and related N-acylethanolamines and expression of cannabinoid receptors and metabolic enzymes across supraspinal and spinal regions 100 days after spared nerve injury (SNI) in male and female rats. SNI increased 2-arachidonoylglycerol (2-AG) and palmitoylethanolamide (PEA) in the prefrontal cortex and 2-AG in the rostral ventromedial medulla in males, with exploratory associations between these measures and reduced pain-related hypersensitivity. In females, SNI increased monoacylglycerol lipase expression in the periaqueductal grey. Additional sex- and hemisphere-dependent differences in ECS components were observed in limbic regions,whereas no significant injury-related changes were detected in spinal cord or plasma. These findings identify regionally distinct ECS alterations during established neuropathic pain and suggest that chronic nerve injury is associated with different patterns of supraspinal ECS plasticity in males and females.

neuroscience↗

bioRxiv2026

The Endocannabinoid System's Contribution to Placebo Analgesia

Placebo analgesia--pain reduction from inert treatments--varies widely across individuals, yet its neurochemical basis remains poorly understood. While endogenous opioids, specifically {beta}-endorphin, contribute to placebo effects, mu-opioid receptor blockade does not fully abolish analgesia, implicating additional systems. Here, we investigate the endogenous cannabinoid (eCB) systems contribution to placebo analgesia in 48 healthy adults using a validated placebo paradigm with blood sampling. We quantified circulating levels of eCB ligands and {beta}-endorphin at baseline, as well as before and after placebo and control conditions to determine condition-related changes. Individual differences in placebo analgesia were associated with increases in fatty acid amide hydrolase (FAAH) substrates--a composite of anandamide, palmitoylethanolamide, and oleoylethanolamide--but not 2-arachidonoylglycerol or {beta}-endorphin alone. Critically, {beta}-endorphin moderated this relationship: FAAH substrates were strongly associated with pain reduction only when {beta}-endorphin levels were low. These findings provide evidence that eCB and opioid systems interact in a state-dependent manner during placebo analgesia in humans, with implications for understanding individual variability in treatment responses.

neuroscience↗

bioRxiv2025

The Contribution of Circulating Endocannabinoid Tone to Individual Differences in Human Pain Sensitivity: A Quantitative Sensory Testing Study

The endocannabinoid (eCB) system--comprising cannabinoid receptors, eCBs (anandamide-- AEA, 2-arachidonoylglycerol--2-AG) and related N-acylethanolamines (NAEs; N-palmitoylethanolamide--PEA, and N-oleoylethanolamide--OEA), and metabolizing enzymes (e.g., fatty acid amide hydrolase; FAAH)--modulates nociceptive circuits in rodents. In humans, the FAAH C385A polymorphism is associated with reduced pain sensitivity, suggesting eCB tone influences individual pain differences, but this has yet to be tested. Here, we determined whether the eCB system is associated with somatosensory and pain sensitivity measured with quantitative sensory testing (QST) in 91 healthy participants (39 males, 52 females). We tested three hypotheses: (1) FAAH C385A polymorphism, cannabis use, and sex affect serum eCB/NAE concentrations; (2) FAAH C385A carriers show altered pain sensitivity versus non-carriers; and (3) baseline serum eCB/NAE concentrations are associated with QST measures. eCB/NAE concentrations were not statistically different based on sex (p > .05), based on FAAH genotype (p > .05), and based on cannabis use (p > .05). To address collinearity of AEA, OEA and PEA, we performed a principal components analysis, which identified a single component of FAAH substrates. Linear regressions found that FAAH genotype did not affect QST measures and that baseline 2-AG and FAAH substrate concentrations were not associated with QST measures, except pressure pain thresholds (PPT; p = 0.003), which were associated with AEA and OEA. Baseline eCB/NAE levels and FAAH genotype are not associated with the outcome measures of standard QST tests that rely on point estimates in healthy adult humans; nonetheless, circulating FAAH substrate levels were associated with PPT.

neuroscience↗

bioRxiv2025

Repeated restraint stress-induced increase in post-surgical somatosensory hypersensitivity and affective responding is mediated by β-adrenergic receptor activation and spinal NLRP3-IL1β signalling in male rats

Pre-surgical stress is a well-recognised risk factor for persistent post-surgical pain, and while the precise underlying neurobiological mechanisms remain unknown, neuro-immune interactions are believed to play a pivotal role. Here, we investigated the effect of repeated restraint stress (RRS) on post-surgical somatosensory hypersensitivity and affective responding in male rats and examined underlying mechanisms mediating these effects. We showed that RRS induced behavioural despair in the forced swim test, reduced body weight gain and elevated faecal corticosterone levels in male Sprague-Dawley rats. Following paw-incision surgery, animals pre-exposed to RRS exhibited exacerbated mechanical and heat hypersensitivity, pain-related aversion, and anxiety-like behaviour compared to non-stress counterparts. RNAseq analysis revealed alterations in glial and neuro-immune pathways in the dorsal horn of the spinal cord in the RRS + paw incision group compared to paw incision alone, data further confirmed by increased microglial activity and inflammatory gene expression (iba1, itgam, il-1{beta} and nlrp3). Intrathecal administration of IL-1Ra or MCC950 (an NLRP3 inhibitor) attenuated the RRS-induced increase in pain-related aversion and mechanical hypersensitivity post-surgery. Chronic administration of RU486, a glucocorticoid receptor antagonist, prevented RRS-induced despair-like behaviour but did not alter the effects of RRS on pain-related aversion or mechanical hypersensitivity post-surgery. In contrast, chronic administration of propranolol, a {beta}-adrenergic receptor antagonist and sympathetic nervous system inhibitor, not only prevented the RRS-induced despair-like behaviour but also attenuated exacerbation of mechanical hypersensitivity, pain-related aversion, and anxiety-like behaviour post-surgery. These findings suggest that RRS exacerbates and prolongs post-surgical somatosensory and affective pain responding via {beta}-adrenergic receptor activation and increased spinal microglial NLRP3-IL1{beta} signalling. These data provide further insight into the mechanisms by which chronic stress and mood disorders exacerbate and prolong post-surgical pain.

neuroscience↗

bioRxiv2020

Disordered phasic relationships between hippocampal place cells, theta, and gamma rhythms in the Ts65Dn mouse model of Down Syndrome

Down Syndrome (DS) in humans is caused by trisomy of chromosome 21 and is marked by prominent difficulties in learning and memory. Decades of research have demonstrated that the hippocampus is a key structure in learning and memory, and recent work with mouse models of DS have shown changes in spectral coherence in the field potentials of hippocampus and regions important for executive function such as prefrontal cortex. One of the primary functional differences in DS is thought to be an excess of GABAergic innervation from Medial Septum (MS) to regions such as hippocampus. In these experiments, we probe in detail the activity of region CA1 of the hippocampus using in vivo electrophysiology in the Ts65Dn mouse model of DS in comparison to their non-trisomic 2N littermates. We find changes in hippocampal phenomenology that suggest that MS output, which drives theta rhythm in the hippocampus, is strongly altered. Moreover, we find that this change affects the phasic relationship of both CA1 place cells and gamma rhythms to theta. Since the phasic relationship of both of these aspects of hippocampal phenomenology to theta are thought to be critical for the segregation of encoding and retrieval epochs within hippocampus, it is likely that these changes are the neural substrates of the learning and memory deficits seen both in human DS and animal models such as Ts65Dn.

neuroscience↗