Publications by authors named "Neil C Ford"

Pain after surgery causes significant suffering. Opioid analgesics cause severe side effects and accidental death. Therefore, there is an urgent need to develop non-opioid therapies for managing post-surgical pain.

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Article Synopsis
  • * Research has shown that a product called Clarix Flo (FLO), derived from human amniotic membranes, can effectively reduce post-surgical pain in mice without the negative effects associated with opioids, by directly acting on pain-signaling neurons.
  • * The study identified a purified component from human amniotic membrane, HC-HA/PTX3, which not only mimics the pain-relief effects of FLO but also works by altering neuron behavior to reduce pain, signaling the potential of biologics from birth tissues as a safer alternative for pain management.
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Unlabelled: Chronic pain after spine surgery (CPSS) is often characterized by intractable low back pain and/or radiating leg pain, and has been reported in 8-40% of patients that received lumbar spine surgery. We conducted a literature search of PubMed, MEDLINE/OVID with a focus on studies about the etiology and treatments of CPSS and low back pain. Our aim was to provide a narrative review that would help us better understand the pathogenesis and current treatment options for CPSS.

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Pain after spinal cord injury (SCI) can be difficult to treat. Drugs that target the opioid receptor (OR) outside the central nervous system (CNS) have gained increasing interest in pain control owing to their low risk of central side effects. Asimadoline and ICI-204448 are believed to be peripherally restricted KOR agonists withlimited access to the CNS.

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The purinergic system plays an important role in pain transmission. Recent studies have suggested that activation of P2-purinergic receptors (P2Rs) may be involved in neuron-satellite glial cell (SGC) interactions in the dorsal root ganglia (DRG), but the details remain unclear. In DRG, P2X7R is selectively expressed in SGCs, which closely surround neurons, and is highly sensitive to 3'-O-(4-Benzoyl) benzoyl-ATP (BzATP).

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The field of research on pain originating from various bone diseases is expanding rapidly, with new mechanisms and targets asserting both peripheral and central sites of action. The scope of research is broadening from bone biology to neuroscience, neuroendocrinology, and immunology. In particular, the roles of primary sensory neurons and non-neuronal cells in the peripheral tissues as important targets for bone pain treatment are under extensive investigation in both pre-clinical and clinical settings.

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Article Synopsis
  • Primary sensory neurons in the dorsal root ganglia are surrounded by satellite glial cells, and their interactions are crucial for how we feel pain.
  • This study used advanced imaging techniques to analyze the activation of these neurons and glial cells in live mice, focusing on how purinergic signaling affects neuronal activity.
  • The findings suggest that targeting purinergic receptors could be a promising approach for controlling pain by altering nociceptive neuron excitability and pain transmission.
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Background: Cannabinoid type-1 receptors (CBRs) are expressed in primary sensory neurones, but their role in pain modulation remains unclear.

Methods: We produced Pirt-CBR conditional knockout (cKO) mice to delete CBRs in primary sensory neurones selectively, and used behavioural, pharmacological, and electrophysiological approaches to examine the influence of peripheral CBR signalling on nociceptive and inflammatory pain.

Results: Conditional knockout of Pirt-CBR did not alter mechanical or heat nociceptive thresholds, complete Freund adjuvant-induced inflammation, or heat hyperalgesia in vivo.

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Various pain therapies have been developed on the basis of the gate control theory of pain, which postulates that nonpainful sensory inputs mediated by large-diameter afferent fibers (Aβ-fibers) can attenuate noxious signals relayed to the brain. To date, this theory has focused only on neuronal mechanisms. Here, we identified an unprecedented function of astrocytes in the gating of nociceptive signals transmitted by neurokinin 1 receptor–positive (NK1R) projection neurons in the spinal cord.

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Skeletal interoception regulates bone homeostasis through the prostaglandin E2 (PGE2) concentration in bone. Vertebral endplates undergo ossification and become highly porous during intervertebral disc degeneration and aging. We found that the PGE2 concentration was elevated in porous endplates to generate spinal pain.

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Agonists to subtype C of the Mas-related G-protein-coupled receptors (MrgC) induce pain inhibition after intrathecal (i.t.) administration in rodent models of nerve injury.

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Mechanisms of visceral pain sensitization and referred somatic hypersensitivity remain unclear. We conducted calcium imaging in Pirt-GCaMP6s mice to gauge responses of dorsal root ganglion (DRG) neurons to visceral and somatic stimulation in vivo. Intracolonic instillation of 2,4,6-trinitrobenzene sulfonic acid (TNBS) induced colonic inflammation and increased the percentage of L6 DRG neurons that responded to colorectal distension above that of controls at day 7.

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Introduction: Paclitaxel-induced peripheral neuropathy (PIPN) is a common dose-limiting side effect of this cancer treatment drug. Spinal cord stimulation (SCS) has demonstrated efficacy for attenuating some neuropathic pain conditions.

Objective: We aim to examine the inhibitory effect of SCS on the development of PIPN pain and changes of gene expression in the spinal cord in male rats after SCS.

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In addition to restoration of bladder, bowel, and motor functions, alleviating the accompanying debilitating pain is equally important for improving the quality of life of patients with spinal cord injury (SCI). Currently, however, the treatment of chronic pain after SCI remains a largely unmet need. Electrical spinal cord stimulation (SCS) has been used to manage a variety of chronic pain conditions that are refractory to pharmacotherapy.

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Spinal projection neurons convey nociceptive signals to multiple brain regions including the parabrachial (PB) nucleus, which contributes to the emotional valence of pain perception. Despite the clear importance of projection neurons to pain processing, our understanding of the factors that shape their intrinsic membrane excitability remains limited. Here, we investigate a potential role for the Na leak channel NALCN in regulating the activity of spino-PB neurons in the developing rodent.

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Mitral and tufted cells in the main olfactory bulb (MOB) of anesthetized rats exhibit vigorous spontaneous activity, action potentials produced in the absence of odor stimuli. The central hypothesis of this paper is that tonic activity of centrifugal input to the MOB modulates the spontaneous activity of MOB neurons. The spontaneous activity of centrifugal fibers causes a baseline of steady-state neurotransmitter release, and odor stimulation produces transient changes in the resulting spontaneous activity.

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Spinal lamina I projection neurons serve as a major conduit by which noxious stimuli detected in the periphery are transmitted to nociceptive circuits in the brain, including the parabrachial nucleus (PB) and the periaqueductal gray (PAG). While neonatal spino-PB neurons are more than twice as likely to exhibit spontaneous activity compared to spino-PAG neurons, the underlying mechanisms remain unclear since nothing is known about the voltage-independent (i.e.

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Pacemaker neurons with an intrinsic ability to generate rhythmic burst-firing have been characterized in lamina I of the neonatal spinal cord, where they are innervated by high-threshold sensory afferents. However, little is known about the output of these pacemakers, as the neuronal populations that are targeted by pacemaker axons have yet to be identified. The present study combines patch-clamp recordings in the intact neonatal rat spinal cord with tract-tracing to demonstrate that lamina I pacemaker neurons contact multiple spinal motor pathways during early life.

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