Biology subjects

Munro, G.

Publications and source records attributed to Munro, G..

3 recordsLinked to original sources

bioRxiv2025

Meteorin resolves nociceptive hypersensitivity by reducing connexin-mediated coupling in satellite glial cells

Neuropathic pain, a persistent condition arising from injury to the nervous system, involves complex interactions between neurons and non-neuronal cells, including satellite glial cells (SGCs) in the dorsal root ganglia (DRG). In this study, we examined the glial-targeting effects of meteorin, a neurotrophic protein with gliogenic properties, using mouse models of neuropathic and inflammatory pain. Systemic meteorin administration reversed mechanical hypersensitivity across diverse neuropathic and inflammatory pain models, with therapeutic effects persisting beyond the treatment period. We identified SGCs as the principal site of meteorin expression and action in the DRG, where it selectively activated SGCs and altered their functional state. Proteomic profiling revealed meteorin-mediated downregulation of gap junction proteins in SGCs, particularly connexin 43, which was corroborated by immunohistochemical analyses. Functional assessments demonstrated that meteorin treatment normalized injury-induced increases in intercellular coupling between SGCs, establishing a mechanistic link between glial network modulation and pain resolution. These findings identify meteorin as a regulator of SGC communication through connexin-dependent mechanisms. The sustained therapeutic effects and multi-model efficacy highlight meteorin as a potential intervention for neuropathic pain while advancing our understanding of SGC plasticity in sensory processing.

neuroscience↗

bioRxiv2024

Persistent changes in nociceptor translatomes govern hyperalgesic priming in mouse models

Hyperalgesic priming is a model system that has been widely used to understand plasticity in painful stimulus-detecting sensory neurons, called nociceptors. A key feature of this model system is that following priming, stimuli that do not normally cause hyperalgesia now readily provoke this state. We hypothesized that hyperalgesic priming occurs due to reorganization of translation of mRNA in nociceptors. To test this hypothesis, we used paclitaxel treatment as the priming stimulus and translating ribosome affinity purification (TRAP) to measure persistent changes in mRNA translation in Nav1.8+ nociceptors. TRAP sequencing revealed 161 genes with persistently altered mRNA translation in the primed state. We identified Gpr88 as upregulated and Metrn as downregulated. We confirmed a functional role for these genes, wherein a GPR88 agonist causes pain only in primed mice and established hyperalgesic priming is reversed by Meteorin. Our work demonstrates that altered nociceptor translatomes are causative in producing hyperalgesic priming.

neuroscience↗

bioRxiv2022

Meteorin alleviates Paclitaxel-induced peripheral neuropathy in mice

Chemotherapy-induced peripheral neuropathy (CIPN) is a challenging condition to treat, and arises due to severe, dose-limiting toxicity of chemotherapeutic drugs such as paclitaxel. This often results in debilitating sensory and motor deficits that are not effectively prevented or alleviated by existing therapeutic interventions. Recent studies have demonstrated the therapeutic effects of Meteorin, a neurotrophic factor, in reversing neuropathic pain in rodent models of peripheral nerve injury induced by physical trauma. Here, we sought to investigate the potential antinociceptive effects of recombinant mouse Meteorin (rmMeteorin) using a paclitaxel-induced peripheral neuropathy model in male and female mice. Paclitaxel treatment (4 x 4mg/kg, i.p.) induced hind paw mechanical hypersensitivity by day 8 after treatment. Thereafter, in a reversal dosing paradigm, five repeated injections of rmMeteorin (0.5 and 1.8mg/kg s.c. respectively) administered over 9 days produced a significant and long-lasting attenuation of mechanical hypersensitivity in both sexes. Additionally, administration of rmMeteorin (0.5 and 1.8mg/kg), initiated before and during paclitaxel treatment (prevention dosing paradigm), blocked the establishment of hind paw mechanical hypersensitivity. Repeated systemic administration of rmMeteorin in both dosing paradigms decreased histochemical signs of satellite glial cell reactivity as measured by glutamine synthetase and connexin43 protein expression in the DRG. Additionally, in the prevention administration paradigm rmMeteorin had a protective effect against paclitaxel-induced loss of intraepidermal nerve fibers. Our findings indicate that rmMeteorin has a robust and sustained antinociceptive effect in the paclitaxel-induced peripheral neuropathy model and the development of recombinant human Meteorin could be a novel and effective therapeutic for CIPN treatment. HighlightsO_LIMeteorin produces an antinociceptive effect in both male and female mice treated with paclitaxel. C_LIO_LISatellite glial cell reactivity induced by paclitaxel treatment is reversed by Meteorin. C_LIO_LIRetraction of intraepidermal nerve fibre (IENF) is blocked by Meteorin treatment in paclitaxel treated mice. C_LIO_LIFindings suggest a disease modifying effect of Meteorin in the mouse model of paclitaxel-induced peripheral neuropathy. C_LI

neuroscience↗