Harnessing the power of endogenous pain control mechanisms for novel therapeutics: how might innovations in neuroimaging help?

Purpose Of Review: This review explores the potential of using novel imaging approaches to deepen our understanding of descending modulatory mechanisms in pain, focussing on functional magnetic resonance imaging (fMRI) of the spinal cord and novel approaches to combining molecular and fMRI data. This review sheds light on the neural processes involved in pain modulation, paving the way for the development of targeted treatments.

Recent Findings: The reviewed literature demonstrates significant advancements in pain research.

From neurotransmitters to networks: Transcending organisational hierarchies with molecular-informed functional imaging.

The human brain exhibits complex interactions across micro, meso-, and macro-scale organisational principles. Recent synergistic multi-modal approaches have begun to link micro-scale information to systems level dynamics, transcending organisational hierarchies and offering novel perspectives into the brain's function and dysfunction. Specifically, the distribution of micro-scale properties (such as receptor density or gene expression) can be mapped onto macro-scale measures from functional MRI to provide novel neurobiological insights.

The effects of propofol anaesthesia on molecular-enriched networks during resting-state and naturalistic listening.

Placing a patient in a state of anaesthesia is crucial for modern surgical practice. However, the mechanisms by which anaesthetic drugs, such as propofol, impart their effects on consciousness remain poorly understood. Propofol potentiates GABAergic transmission, which purportedly has direct actions on cortex as well as indirect actions via ascending neuromodulatory systems.

Improving neuropathic pain treatment - by rigorous stratification from bench to bedside.

Chronic pain is a constantly recurring and persistent illness, presenting a formidable healthcare challenge for patients and physicians alike. Current first-line analgesics offer only low-modest efficacy when averaged across populations, further contributing to this debilitating disease burden. Moreover, many recent trials for novel analgesics have not met primary efficacy endpoints, which is particularly striking considering the pharmacological advances have provided a range of highly relevant new drug targets.

Neurotransmitter receptor densities are associated with changes in regional Cerebral blood flow during clinical ongoing pain.

Arterial spin labelling (ASL) plays an increasingly important role in neuroimaging pain research but does not provide molecular insights regarding how regional cerebral blood flow (rCBF) relates to underlying neurotransmission. Here, we integrate ASL with positron emission tomography (PET) and brain transcriptome data to investigate the molecular substrates of rCBF underlying clinically relevant pain states. Two data sets, representing acute and chronic ongoing pain respectively, were utilised to quantify changes in rCBF; one examining pre-surgical versus post-surgical pain, and the second comparing patients with painful hand Osteoarthritis to a group of matched controls.

Differential contributions of serotonergic and dopaminergic functional connectivity to the phenomenology of LSD.

Rationale: LSD is the prototypical psychedelic. Despite a clear central role of the 5HT receptor in its mechanism of action, the contributions of additional receptors for which it shows affinity and agonist activity remain unclear.

Objectives: We employed receptor-enriched analysis of functional connectivity by targets (REACT) to explore differences in functional connectivity (FC) associated with the distributions of the primary targets of LSD-the 5HT, 5HT, 5HT, D1 and D2 receptors.

Pain in neurodegenerative diseases with atypical parkinsonism: a systematic review on prevalence, clinical presentation, and findings from experimental studies.

Parkinson's disease-related pain has increasingly been investigated in research studies. Still, only a few studies have addressed the prevalence and clinical characteristics of pain in neurodegenerative disorders with atypical parkinsonism. The existing evidence, although scarce, suggests that, similarly as in Parkinson's disease, individuals with neurodegenerative diseases with atypical parkinsonism might be predisposed to the development of persistent pain.

Cerebellar involvement in hallucinations may transcend clinical conditions and perceptual modalities.

Our recent neuroimaging study identified structural differences in cerebellar subfields linked to cortical attentional networks in patients with eye disease or Parkinson's disease who experience visual hallucinations and a commentary on the study by Zorzi et al. provided additional evidence of functional cerebellar changes in Dementia with Lewy bodies. Here, we review evidence for cerebellar involvement in hallucinations across multiple clinical conditions and sensory modalities as well as examine its wider clinical and mechanistic implications.

Cerebellar correlates of visual hallucinations in Parkinson's disease and Charles Bonnet Syndrome.

Hallucinations, percepts in the absence of external stimuli, are a shared feature of eye-disease (Charles Bonnet Syndrome, CBS) and Parkinson's disease (PD) thought to arise through pathophysiologically distinct mechanisms: deafferentation and attentional network dysfunction respectively. Recent studies have found an association between visual hallucinations and structural changes in the cerebellum without obvious link to either mechanism. Here, we employed Voxel Based Morphometry (VBM), optimised for the cerebellum using the Spatially Unbiased Infratentorial Template (SUIT), to characterise similarities and differences in cerebellar structure associated with visual hallucinations in PD and CBS.