Biology subjects

Bonet, I. J. M.

Publications and source records attributed to Bonet, I. J. M..

2 recordsLinked to original sources

bioRxiv2023

The Primary Cilium and its Hedgehog Signaling in Nociceptors Contribute to Inflammatory and Neuropathic Pain

The primary cilium, a 1-3 m long hair-like structure protruding from the surface of almost all cells in the vertebrate body, is critical for neuronal development and also functions in the adult. As the migratory neural crest settles into dorsal root ganglia (DRG) sensory neurons elaborate a single primary cilium at their soma that is maintained into adult stages. While it is not known if primary cilia are expressed in nociceptors, or their potential function in the mature DRG neuron, recent studies have shown a role for Hedgehog, whose signaling demonstrates a dependence on primary cilia, in nociceptor sensitization. Here we report the expression of primary cilia in rat and mouse nociceptors, where they modulate mechanical nociceptive threshold, and contribute to inflammatory and neuropathic pain. When siRNA targeting Ift88, a primary cilium-specific intra-flagellar transport (IFT) protein required for ciliary integrity, was administered by intrathecal injection, in the rat, it resulted in loss of Ift88 mRNA in DRG, and primary cilia in neuronal cell bodies, which was associated with an increase in mechanical nociceptive threshold, and abrogation of hyperalgesia induced by the pronociceptive inflammatory mediator, prostaglandin E2, and painful peripheral neuropathy induced by a neurotoxic chemotherapy drug, paclitaxel. To provide further support for the role of the primary cilium in nociceptor function we also administered siRNA for another IFT protein, Ift52. Ift52 siRNA results in loss of Ift52 in DRG and abrogates paclitaxel-induced painful peripheral neuropathy. Attenuation of Hedgehog-induced hyperalgesia by Ift88 knockdown supports a role for the primary cilium in the hyperalgesia induced by Hedgehog, and attenuation of paclitaxel chemotherapy-induced neuropathy (CIPN) by cyclopamine, which attenuates Hedgehog signaling, suggests a role of Hedgehog in CIPN. Our findings support a role of nociceptor primary cilia in the control of mechanical nociceptive threshold and in inflammatory and neuropathic pain, the latter, at least in part, Hedgehog dependent.

neuroscience↗

bioRxiv2019

Physical Activity Induces Nucleus Accumbens Genes Expression Changes Preventing Chronic Pain Susceptibility Promoted by High-Fat Diet and Sedentary Behavior in Mice

High-fat diet (HFD)-induced obesity was reported to increase pain behavior independent of obesity status in rats, whereas weight loss interventions such as voluntary physical activity (PA) for adults with overweight or obesity was reported to promote pain reduction in humans with chronic pain (CP). However, is unknown whether an HFD and sedentary (SED) behavior is underlying to CP susceptibility and whether voluntary PA can prevent it. Moreover, differential gene expression in the nucleus accumbens (NAc) is considered to play a crucial role in CP susceptibility. The present study used an adapted model of the inflammatory prostaglandin E2 (PGE)-induced persistent hyperalgesia (PH-ST) protocol for mice, an HFD, and a voluntary PA paradigm to test these hypotheses. In addition, we performed a transcriptome in the NAc and a gene ontology enrichment tools to investigate the differential gene expression and identify the biological processes associated with CP susceptibility tested here. Our results demonstrated that HFD and sedentary behavior promoted CP susceptibility, which in turn was prevented by voluntary PA, even when the animals were fed an HFD. Transcriptome in the NAc found 2,204 differential expression genes related CP susceptibility promoted by HFD and sedentary behavior and prevented by voluntary PA. The gene ontology enrichment revealed 41 biological processes implicated in CP susceptibility. Analyzing collectively those biological processes, our results suggested that genes related to metabolic and mitochondria stress were up-regulated in the CP susceptibility group, whereas genes related to neuroplasticity and axonogenesis were up-regulated in the CP prevented group. These findings provide pieces of evidence that an HFD and sedentary behavior promoted gene expression changes in the NAc related to neurodegeneration and those changes were also underlying to CP susceptibility. Additionally, our findings confirmed other findings supporting the crucial role of voluntary PA to prevent CP susceptibility and add novel insights of differential gene expression in the NAc related to neuroplasticity.

neuroscience↗