Euphorbia Bicolor Phytochemicals Reduce Oxidative Stress, Inflammatory Mediators, and Pain Signaling in a Rat Model of Burn Pain
Pain associated with burn injury has been linked to oxidative stress, inflammation, and nociceptor sensitization and can lead to chronic pain. Burn pain is challenging to manage with non-steroidal anti-inflammatory drugs, opioids, and gabapentinoids; all of which are linked to undesirable side effects. Novel strategies that mitigate burn pain are needed. Euphorbia bicolor, a native Texas plant, contains phytochemicals that could serve as a novel analgesic(s). We hypothesized that E. bicolor phytochemicals reduce pain and inflammatory key markers present in the blood, sensory ganglia, and spinal cord that contribute to burn...
Source: The Journal of Pain - April 1, 2024 Category: Materials Science Authors: Temiloluwa P. Olaoluwa, DiAnna L. Hynds, Camelia Maier, Dayna L. Averitt Source Type: research
Exploring Cellular Mechanisms of Inflammatory Temporomandibular Joint Pain by Single-Cell Multiomic Sequencing
In this study, we aimed to identify cell-specific gene targets in the Sp5C for TMD-like pain using single-cell multiomic sequencing. Complete Freund's Adjuvant (CFA) was injected into mouse temporomandibular joint (TMJ) to induce inflammatory TMD-like pain. (Source: The Journal of Pain)
Source: The Journal of Pain - April 1, 2024 Category: Materials Science Authors: Ran Tao, Sufang Liu, Joshua Crawford, Charles Winslow, Feng Tao Source Type: research
Exploring the Role of Descending Dopamine Pain Modulation in the Transition to Chronic Pain
Changes in the central nervous system and descending pain modulation may underlie the transition to chronic pain, but our understanding of these changes is insufficient to predict and prevent the transition to chronic pain. The descending dopamine pain modulation system originates in the A11 nucleus of the hypothalamus and projects ipsilaterally to all levels of the spinal cord. A faciliatory role has been suggested for spinal dopamine in animals vulnerable to chronic pain from a prior inflammatory insult. (Source: The Journal of Pain)
Source: The Journal of Pain - April 1, 2024 Category: Materials Science Authors: Angela F. Smith, Kazuhiro Hayashi, Adam J. Janowski, Ashley N. Plumb, Kathleen A. Sluka Source Type: research
Fibroblast Growth Factor Receptor 3 Autoantibodies Induce Hyperexcitability in Sensory Neurons and Pain Behaviors
Small fiber neuropathies (SFN) result from primary degeneration of the sensory neurons of the dorsal root ganglia (DRG), more specifically, the A δ (mechanoreceptors) and unmyelinated C-fibers (nociceptors). The clinical presentation is often symmetric and can present as a painful length-dependent sensory predominant polyneuropathy. Here, we utilize autoantibodies against fibroblast growth factor receptor 3 (FGFR3) as a biological marker of a population of patients with SNN and SFN. We have found that FGFR3 autoantibodies bind neuronal soma within rat dorsal root ganglia (DRG), confirming FGFR3 expression in the primary a...
Source: The Journal of Pain - April 1, 2024 Category: Materials Science Authors: Lyuba Salih, Nicolas Dumaire, Christine Kim, Liberty Francois-Moutal, Aubin Moutal Source Type: research
Fibroblast-derived PI16 Drives the Physiological Process of Immune Cell Recruitment and Activation During Inflammatory Response
Chronic inflammatory pain affects over one-quarter of United States citizens (Dydyk, 2023). The extent and impact of chronic inflammatory pain is determined by myeloid cell-driven induction and resolution of inflammation. In previous studies, we have shown that PI16 (peptidase inhibitor 16), a fibroblast-derived protein of unknown function, controls neuropathic pain by facilitating crosstalk between fibroblasts at the endothelial barrier (Sighmar, 2020). We also showed that PI16 sustains Complete Freund ’s Adjuvant (CFA)-induced inflammatory pain (Garrity, 2023). (Source: The Journal of Pain)
Source: The Journal of Pain - April 1, 2024 Category: Materials Science Authors: Rachelle Garrity, Areeful Haque, Annemieke Kavelaars, Cobi Heijnen, Andrew Shepherd Source Type: research
Genetic Characterization and Exploration of Mu-Opioid Receptor Signaling in C. elegans
Opioids are the most potent pain killers available but feature severe negative side effects, highlighting the need for safer analgesic drugs. The key receptor that mediates analgesia and problematic side effects is the mu-opioid receptor (MOR). Mammalian studies have suggested MOR principally signals though Gai with relatively little known about the role of Gao in MOR signaling. Our lab pioneered the development of a cross-species transgenic Caenorhabditis elegans model expressing mammalian MOR (tgMOR) that yields opioid-induced behavior as its primary readout. (Source: The Journal of Pain)
Source: The Journal of Pain - April 1, 2024 Category: Materials Science Authors: Deziree L. Coleman, Rachel J. Ren, Karla J. Opperman, Brock Grill Source Type: research
G-Protein Coupled Receptor 160 Inhibition Prevents the Development of Oxaliplatin-Induced Neuropathic Pain and Alteration of Perineuronal Net in the Spinal Cord of Rats
Peripheral neuropathy accompanied by a treatment resistant neuropathic pain syndrome is a major dose-limiting toxicity of platinum-based chemotherapeutics used to treat colorectal cancer, such as oxaliplatin. Our recent studies linked GPR160 in the spinal cord to the development of pain. However, little is known of the role of GPR160 in chemotherapy-induced neuropathic pain syndromes. Here, we tested whether GPR160 in the spinal cord contributes to the development of hypersensitivities and central sensitization in a rat model of oxaliplatin-induced neuropathic pain. (Source: The Journal of Pain)
Source: The Journal of Pain - April 1, 2024 Category: Materials Science Authors: Timothy M. Doyle, Caron M. Harada, Zhoumou Chen, Jinsong Zhang, Daniela Salvemini Source Type: research
Heat-Treatment Precipitates Latent Painful Neuropathy in Rats with Fabry Disease
Fabry disease is the most common lysosomal storage disorder —affecting as many as 1:1600 males—and arises from mutations in the X-linked gene GLA. Patients with Fabry disease develop painful small-fiber neuropathy during adolescence, which is accompanied by episodic pain that is induced by heat, fever, or exercise. While Gla-KO Fabry rats exhibit pain-li ke behaviors, they incompletely capture patient phenotypes and only develop robust sensory phenotypes later during their lifespan. To address this clinical-preclinical discrepancy, we asked whether early exposure to heat-stress could precipitate a latent painful neurop...
Source: The Journal of Pain - April 1, 2024 Category: Materials Science Authors: Jonathan David Enders, Eve Prodoehl, Anvitha Sriram, Dianise M. Rodriguez Garcia, Bhavya Dharanikota, Cheryl L. Stucky Source Type: research
Identification Of Drug Treatments That Stimulate C-Fiber Regeneration
Small fiber neuropathy (SFN) is a widespread complication that leads to pain, burning, or loss of sensation in the distal limbs. A hallmark of SFN is a loss of intraepidermal nerve fibers (IENF). Currently, therapeutic options for humans with SFN are severely lacking. However, preclinical studies have identified numerous drugs that stimulate IENF regeneration in rodents but have not yet translated to human use. Here, we leveraged existing information from published articles to identify all drugs that have reported IENF regenerative effects in rodents. (Source: The Journal of Pain)
Source: The Journal of Pain - April 1, 2024 Category: Materials Science Authors: Lana Heslop, Sarah Crowards, Douglas Wright Source Type: research
Immunologic Synapse Formation Between Mouse Dorsal Root Ganglion Neurons and CD4+ T Cells Induces CD4+ T Cell Cytokine Production
Chemotherapy can be a life-saving treatment, but development of chemotherapy-induced peripheral neuropathy (CIPN) is a major dose-limiting toxicity. Recent studies demonstrate that paclitaxel (PTX) increases anti-inflammatory CD4+ T cells in the dorsal root ganglia (DRG), and that T cells and anti-inflammatory cytokines are protective against CIPN. We found that DRG neurons express major histocompatibility II (MHCII) protein, and that reducing neuronal MHCII exacerbates PTX-induced cold hypersensitivity in male and female mice. (Source: The Journal of Pain)
Source: The Journal of Pain - April 1, 2024 Category: Materials Science Authors: Emily E. Whitaker, Diana J. Goode Source Type: research
Impact of Resiniferatoxin on Oral Squamous Cell Carcinoma Pain and Tumor-Associated Immune Response
Oral squamous cell carcinoma (oSCC) is one of the most painful cancers. TRPV1+ nociceptive afferents have been implicated in cancer pain and immunosuppression. We hypothesize that prophylactic denervation of peptidergic sensory neurons using resiniferatoxin (RTX) will reduce cancer pain and improve anti-tumor immunity. To test this hypothesis, we used syngeneic orthotopic transplant mouse models. Nociceptive behavior and nerve injury were assessed using the dolognawmeter and immunohistochemistry, respectively. (Source: The Journal of Pain)
Source: The Journal of Pain - April 1, 2024 Category: Materials Science Authors: Kathryn T. Eskew, Lisa A. Mcllvried, Andre M. Martel Matos, Megan A. Atherton, Nicole N. Scheff Source Type: research
Increased Mechanical Hypersensitivity Resulting from the Loss of Sigma-2 Receptor/Transmembrane Protein 97 Expression in Both Germline and Nociceptor-Specific Context
The Sigma-2 receptor ( σ2/TMEM97), recently identified as Tmem97, is a transmembrane protein that is located in the endoplasmic reticulum (ER) and the plasma membrane. While the literature has highlighted ligands targeting Tmem97 for anti-neuropathic effects, its involvement in inflammatory pain-like responses remains un derstudied compared to neuropathic pain. Here, we aim to characterize Tmem97-associated inflammatory pain-like behaviors using global Tmem97 knockout (KO) and conditional Tmem97 knockout mice (cKO). (Source: The Journal of Pain)
Source: The Journal of Pain - April 1, 2024 Category: Materials Science Authors: Veronica M. Hong, Avaneesh Rade, Zubab Syed, Muhammad Saad Yousuf, Daniel J. Liebl, Stephen Martin, Theodore J. Price, Benedict J. Kolber Source Type: research
Inflammatory Response in Peripheral and Central Nervous System Is Involved in Alzheimer ’s Disease Associated Pain
Neuropathic pain often occurs in older people, particularly in the patients with neurodegenerative diseases such as Alzheimer ’s disease (AD) related dementia (ADRD). The abnormality of pain response may be an early indicator of memory loss and cognitive impairment. Increasing evidence suggests that the chronic inflammation occurring in the brain of AD patients seems to be triggered by increased amyloid beta (Aβ) accumu lation. However, whether this inflammation in the peripheral and central nervous system (CNS) exacerbates the neuropathic pain and the progression of ADRD remains unclarified. (Source: The Journal of Pain)
Source: The Journal of Pain - April 1, 2024 Category: Materials Science Authors: Ying Xu Source Type: research
Interleukin-10-producing Monocytes Contribute to Sex Differences in Pain Resolution in Mice and Humans
Pain is closely associated with the immune system, which exhibits sexual dimorphism. For these reasons, neuro-immune interactions are suggested to drive sex differences in pain pathophysiology. However, the impact of peripheral neuro-immune interactions on sex differences in pain resolution remains limited. Here, we have shown, in both a mouse model of inflammatory pain and in humans following traumatic pain, that males had higher levels of interleukin (IL)-10 than females, which were correlated with faster pain resolution. (Source: The Journal of Pain)
Source: The Journal of Pain - April 1, 2024 Category: Materials Science Authors: Jaewon Sim, Elizabeth O'Guin, Karli Monahan, Chiho Sugimoto, Samuel McLean, Liz Albertorio-Saez, Ying Zhao, Sophie Laumet, Andrew Dagenais, Matthew Bernard, Joseph Folger, Alfred Robison, Sarah Linnstaedt, Geoffroy Laumet Source Type: research
Keratinocyte Piezo1 Mediates Paclitaxel-Induced Mechanical Hypersensitivity
In this study, we used inhibitory optogenetic and chemogenetic techniques to determine if keratinocytes contribute to the mechanical hypersensitivity induced by treatment with the chemotherapeutic drug Paclitaxel. We found that keratinocyte inhibition largely alleviates paclitaxel-induced mechanical hypersensitivity in mice. (Source: The Journal of Pain)
Source: The Journal of Pain - April 1, 2024 Category: Materials Science Authors: Alex Mikesell, Olena Isaeva, Cheryl Stucky Source Type: research
