Biology subjects

Maiaru, M.

Publications and source records attributed to Maiaru, M..

5 recordsLinked to original sources

bioRxiv2026

An Optimised Method for Robust Golgi Cox Staining in Cortical Neurons

Golgi-based staining remains a valuable method for visualising the full morphology of individual neurons, however conventional workflows can be slow, variable, and technically demanding. Here, we present a modified staining protocol designed to provide a practical workflow for Golgi-based labelling in mouse cortical tissue. The revised workflow combines controlled fixation, dichromate impregnation, silver development, vibratome sectioning, and slide processing conditions that support visualisation of neuronal somata and dendritic architecture. In the tissue examined here, the protocol produced stained tissue with discernible neuronal morphology and was suitable for morphological assessment using standard light microscopy and image analysis software. Overall, this method may be useful for laboratories seeking a straightforward and cost-conscious protocol for neuronal morphology.

neuroscience↗

bioRxiv2026

Transient silencing of spinal nociceptive neurons leads to a long-term reduction in joint pain mediated by recruitment of opioid activity.

Chronic inflammatory joint pain remains inadequately treated despite current therapies, creating urgent clinical need for non-addictive alternatives in an era of heightened opioid-related concerns. A promising new approach involves conjugates of botulinum toxin and substance P (SP-BOT), which, when infused locally or spinally, have been shown to produce temporary pain relief in neuropathic mouse models, with its effects declining after approximately 100 days as the construct loses activity. However, its long-term efficacy in inflammatory pain models was unknown. Unexpectedly, in a mouse model of ankle inflammatory arthritis, a single intrathecal injection of SP-BOT at the peak of pain sensitivity produced a persistent reduction in mechanical hyperalgesia that lasted for weeks beyond the loss of construct activity. Furthermore, this late-phase pain relief exhibited a striking mechanism in that a single injection of the opioid antagonist naltrexone partially reversed the anti-hyperalgesia generated by SP-BOT. These data indicate that SP-BOT-mediated neuronal silencing initiates two distinct phases of pain relief. An initial, direct phase is followed by a second, sustained phase that maintains pain alleviation and is driven by endogenous opioid mechanisms.

pharmacology and toxicology↗

bioRxiv2025

Psilocybin ameliorates neuropathic pain-like behaviour in mice and facilitates gabapentin-mediated analgesia

Chronic pain states are challenging to control with current drug therapies. Here, we demonstrate that a single dose of psilocybin can produce a sustained anti-nociceptive effect in a model of chronic neuropathic pain in male and female mice. Psilocybin anti-nociceptive effects were mediated by 5-HT2A receptors, although additional mechanisms might also be involved. Furthermore, a single dose of psilocybin caused a significant increase in the anti-nociceptive potential of gabapentin, a widely used treatment for neuropathic pain consistent with the establishment of longer lasting changes in network processing. Overall, these findings present the first preclinical evidence that psilocybin could be a valuable approach for treating chronic pain from nerve injury and serve as a new therapeutic addition for pain management.

neuroscience↗

bioRxiv2022

Using the DNA methylation profile of the stress driver gene FKBP5 for chronic pain diagnosis

Epigenetic changes can bring insight into gene regulatory mechanisms associated with disease pathogenicity, including chronicity and increased vulnerability. To date, we are yet to identify genes sensitive to epigenetic regulation that contribute to the maintenance of chronic pain and with an epigenetic landscape indicative of the susceptibility to persistent pain. Such genes would provide a novel opportunity for better pain management, as their epigenetic profile could be targeted for the treatment of chronic pain or used as an indication of vulnerability for prevention strategies. Here, we investigated the epigenetic profile of the gene FKBP5 for this potential, using targeted bisulphite sequencing in rodent pre-clinical models of chronic and latent hypersensitive states. The FKBP5 promoter DNA methylation (DNAm) signature in the CNS was significantly different between models of persistent pain and there was a significant correlation between CNS and peripheral blood FKBP5 DNAm, indicating that further exploration of FKBP5 promoter DNAm as a biomarker of chronic pain pathogenic origin is warranted. We also found that maternal separation, which promotes the persistency of inflammatory pain in adulthood, was accompanied by long-lasting reduction in FKBP5 DNAm, suggesting that FKPB5 DNAm profile may indicate the increased vulnerability to chronic pain in individuals exposed to trauma in early life. Overall, our data demonstrate that the FKBP5 promoter DNAm landscape brings novel insight into the differing pathogenic origins of chronic pain, may be able to diagnose and stratify patients, and predict the susceptibility to chronic pain.

neuroscience↗

bioRxiv2020

The alleviation of neuropathic pain behaviours by a single injection of a synthetic substance P-botulinum conjugate persists for up to 120d and can be restored with a second injection of conjugate.

There is an urgent need for new pain-relieving therapies. We have previously shown using mouse models of persistent pain that a single intrathecal injection of substance P conjugated to the light chain of botulinum toxin (SP-BOT) silenced neurons in the dorsal horn of the spinal cord and alleviated mechanical hypersensitivity. The SP-BOT construct selectively silenced neurokinin 1 receptor positive (NK1R+) neurons in the superficial dorsal horn of the spinal cord. A subset of these NK1R+ neurons are nociceptive projection neurons and convey injury-related information to the brainstem, initiating and maintaining programmes of escape and recovery essential for healing. Previously, we observed a reduction in mechanical hypersensitivity in a spared nerve injury (SNI) model of neuropathic pain state after intrathecal injection of SP-BOT over the lumbar spinal cord and lasting for up to 40 days. In this latest study, we have extended these observations and now show that thermal and affective measures of pain behaviour were also alleviated by a single intrathecal injection of SP-BOT. By introducing SNI 30 days, 60 days, 90 days or 120 days after injection of SP-BOT we have established that NK1R+ spinal neurons in the superficial lamina of the dorsal horn were silenced for up to 120 days following a single intrathecal injection of the botulinum construct. We also show that behavioural alleviation of neuropathic pain symptoms could be reinstated by a second injection of SP-BOT at 120 days. Taken together this research demonstrates that this recently developed botulinum toxin conjugate provides a powerful new way of providing long term pain relief without toxicity following a single injection and also has a therapeutic potential for repeated dosing when pain begins to return.

neuroscience↗