Pharmacology of Classical Psychedelic in Mouse Models of Chronic Pain
In this study, we aim to investigate the effect of two classical psychedelics (DOI and psilocybin) in mouse models of paclitaxel-induced peripheral neuropathy (CIPN) and CFA chronic Inflammatory pain. (Source: The Journal of Pain)
Source: The Journal of Pain - April 1, 2024 Category: Materials Science Authors: M. Imad Damaj, Eda Koseli, Belle Buzzi, Yogesh Rakholia, Melissa Lewis, Javier Gonz ález-Maeso Source Type: research
Plant-Derived Natural Product Guggulipid Alleviates Trigeminal Neuropathic Pain in Mice
One type of chronic pain that is particularly traumatic for patients is trigeminal neuropathic pain, which is caused by inflammation and demyelination of the trigeminal nerve pathways. Commiphora mukul, is well known in the traditional Indian system of medicine, and has been used to treat ailments such as obesity, bone fractures, arthritis, inflammation, cardiovascular diseases, and lipid disorders. Here we investigated the effect of guggulipid, a neutral fraction of ethyl acetate extract of gum resin of the Commiphora mukul Engl. (Source: The Journal of Pain)
Source: The Journal of Pain - April 1, 2024 Category: Materials Science Authors: Sachin Goyal, Karin N. Westlund, Sascha R.A. Alles Source Type: research
Population Level Profiling of Primary Afferent Neuronal Activity in Response to Epinephrine Using Two-Photon Calcium Imaging
Stress in the face of overwhelming danger triggers activation of the sympathetic nervous system and leads to systemic release of epinephrine. Engagement of this system and the release of epinephrine can suppress incoming noxious information to allow for escape and survival from potentially threatening situations. However, the degree to which circulating epinephrine alters the activity of primary afferents is not known. Moreover, it is not clear whether epinephrine differentially modulates distinct subtypes of afferents and, if so, which ones. (Source: The Journal of Pain)
Source: The Journal of Pain - April 1, 2024 Category: Materials Science Authors: Harrison J. Stratton, Charlies Warwick, H. Richard Koerber, Sarah E. Ross Source Type: research
Preclinical Assessment of Opioid Tolerance: Methodological Problems and Solutions
Although opioids are the most effective treatment for pain, their use in treating chronic pain is limited by the development of tolerance with prolonged use. A major goal of preclinical research is to identify the neural mechanisms underlying opioid tolerance so these mechanisms can be disrupted to prolong the analgesic effects. Approximately 100 neural mechanisms of opioid tolerance have been reported. Some of these mechanisms are the result of distinct types of tolerance and some of these are the result of poor experimental design. (Source: The Journal of Pain)
Source: The Journal of Pain - April 1, 2024 Category: Materials Science Authors: Michael M. Morgan Source Type: research
Primary Afferents Containing Calcitonin Gene-Related Peptide and Substance P Form Complex Synaptic Arrangements in Human Spinal Dorsal Horn
Unmyelinated C-fibres have been classically defined as peptidergic or non-peptidergic based on the presence or absence of calcitonin gene-related peptide and/or substance P. Peptidergic primary afferents terminate in lamina I of the rodent spinal dorsal horn, where they form simple synaptic arrangements. In contrast, the axonal boutons of non-peptidergic afferents make multiple output synapses and have been shown to form the central axon of type I glomeruli. There is an expansion in the expression of these peptides in humans as a greater proportion of primary afferents contain the mRNA for the peptide precursor proteins th...
Source: The Journal of Pain - April 1, 2024 Category: Materials Science Authors: Olivia Davis, Robert Kerr, Andrew Todd, Theodore Price Source Type: research
Probiotic Treatment Alleviates Chronic Pain in Sickle Cell Disease Mice
Chronic pain is a primary complication for those suffering from sickle cell disease, a genetic blood disorder. The basis of chronic sickle cell disease pain is not completely resolved, and thus, analgesic offerings have limited efficacy. Using transgenic mice, our lab recently determined that the gut microbiota contributes to chronic sickle cell disease pain. Fecal material transplant from sickle cell disease mice into pseudo-germfree animals induced persistent mechanical and cold allodynia in recipients, phenotypes that mirrored donor behaviors. (Source: The Journal of Pain)
Source: The Journal of Pain - April 1, 2024 Category: Materials Science Authors: McKenna L. Pratt, Mandee K. Schaub, Gregory Dussor, Katelyn E. Sadler Source Type: research
Radiation Of Pain in Humans: Evidence for A Psychophysical Manifestation of a Neural Population Coding Mechanism?
How localized pain becomes widespread is unclear. Here, we hypothesize that more intense noxious stimuli lead to greater areas of perceived pain, but more intense light does not produce radiation. Three noxious (45, 47 and 49 °C) and one innocuous (43°C) intensity stimuli were applied to glabrous (hand) and hairy skin (forearm) skin with 5s and 10s stimuli. Control stimuli comprised four different intensities of visual stimuli displayed on the target bodily areas. Healthy participants (N=50) provided pain (and light) i ntensity ratings as well as pain (and light) extent ratings. (Source: The Journal of Pain)
Source: The Journal of Pain - April 1, 2024 Category: Materials Science Authors: Waclaw M. Adamczyk, Vishwanath Ramu, Catherine Jackson, Geraldine Schulze, Kenneth R. Goldschneider, Susmita Kashikar-Zuck, Christopher D. King, Robert C. Coghill Source Type: research
Role Of Truncated Tropomyosin Receptor Kinase B In Oral Cancer Pain
We previously demonstrated that brain-derived neurotrophic factor (BDNF) released from oral squamous cell carcinoma (OSCC) cells orchestrate oral cancer-induced pain transmission, that is reversed by locally inhibiting its receptor, TrkB, at the site of oral tumor growth. The truncated isoform (TrkBTK-), lacking the tyrosine kinase domain, was shown to be the predominant isoform expressed in oral cancers. Therefore, our current study explores the contribution of peripheral truncated TrkB isoform in mediating oral cancer pain. (Source: The Journal of Pain)
Source: The Journal of Pain - April 1, 2024 Category: Materials Science Authors: Jaclyn Merlo, Tarek Ibrahim, Ping Wu, Shivani Ruparel Source Type: research
Sensitization Of Epidermal Transient Receptor Potential Vanilloid 4 Receptor in Paclitaxel Model of Chemotherapy-Induced Peripheral Neuropathy
Recent studies suggest that systemic inhibition of the Transient Receptor Potential Vanilloid 4 (TRPV4) cation channel or complete removal of TRPV4 globally results in significant improvements in alleviating the painful peripheral neuropathy induced by chemotherapy agents. TRPV4 is expressed in various tissues, where it plays a crucial role in normal functioning, contributing to the perception and processing of various sensory modalities, as well as the regulation of cardiovascular, respiratory, and renal functions. (Source: The Journal of Pain)
Source: The Journal of Pain - April 1, 2024 Category: Materials Science Authors: Elena Isaeva, Alexander Mikesell, Anvitha Sriram, Bhavya Dharanikota, Cheryl Stucky Source Type: research
Single Cell Transcriptomics of Mouse Epidermis Reveals a Pivotal Role of Langerhans Cells in Painful Diabetic Neuropathy
Painful diabetic neuropathy (PDN) is one of the most common and intractable complications of diabetes, resulting in remodeling of the cutaneous innervation and neuropathic pain. Accumulating evidence suggests the crucial role epidermal non-neuronal cells for the development of PDN. To understand how epidermal cells communicate with cutaneous afferents and how this communication affects PDN, we performed single-cell RNA sequencing of the epidermis of mice fed a high-fat diet (HFD) for 10 weeks. We captured the gene expression profile of keratinocytes and non-keratinocytes cells, including Langerhans cells (LCs). (Source: The Journal of Pain)
Source: The Journal of Pain - April 1, 2024 Category: Materials Science Authors: Paola Pacifico, Nirupa D. Jayaraj, Dongjun Ren, James S. Coy-Dibley, Abdelhak A. Belmadani, Dale George, Richard J. Miller, Daniela M. Menichella Source Type: research
Single-nuclei Ribonucleic Acid Sequencing Shows Unique Transcriptomic Signatures of Rat Dorsal Root Ganglia in a Disc-associated Chronic Low Back Pain Model
Patients with disc-associated chronic low back pain (cLBP) and knee osteoarthritis (OA) often display aberrant innervation of nociceptors into the joint. Repeated stimulation or damage of nociceptors in joints can cause peripheral sensitization. Nav1.7 and Piezo2 are ion channels upregulated in dorsal root ganglia (DRGs) in painful knee OA animal models with peripheral sensitization. Despite these data, changes in DRG gene expression in human or animal models of cLBP are mostly unknown. Further, there is limited comprehensive single nucleus RNA sequencing (snRNAseq) of rat DRGs. (Source: The Journal of Pain)
Source: The Journal of Pain - April 1, 2024 Category: Materials Science Authors: Sydney M. Caparaso, Ishwarya Sankaranarayanan, Theodore J. Price, Rebecca A. Wachs Source Type: research
Spinal Cord Injury-Induced Chronic Pain is Driven by a Central to Peripheral Interleukin-1 Mediated Signaling Pathway
Spinal cord injury (SCI) is associated with the development of treatment-resistant chronic pain that most commonly presents below the level of injury. Novel therapeutics are essential to reduce risk of chronic pain development and improve functional recovery. We and others have shown that SCI causes an increase in below-level nociceptor hyperactivity that is associated with the development and persistence of below-level pain. The mechanism responsible for this increase in below-level nociceptor activity is not well understood, but whole transcriptome RNA sequencing of the spinal cord and DRG has suggested that SCI increase...
Source: The Journal of Pain - April 1, 2024 Category: Materials Science Authors: SN Varghese, OC Eller, EE Young, KM Baumbauer Source Type: research
Spinal Microglia Maintain Multiple Sclerosis-Associated Neuropathic Pain
The contribution of microglia to multiple sclerosis associated neuropathic pain (MSNP) is poorly understood. Adult male and female mice, some created with tamoxifen-inducible CX3CR1-CreER::hM4Di-DREADD transgenes, underwent experimental autoimmune encephalomyelitis with the subcutaneous injection of MOG33-55 and complete Freund ’s adjuvant in the absence of pertussis toxin (EAE-nPTX). EAE-nPTX mice rapidly developed plantar hypersensitivity to mechanical and cold stimuli, and then they and their controls (CFA without MOG35-55 and naïve groups without injections) received either: 1) Global CNS depletion of microglia with...
Source: The Journal of Pain - April 1, 2024 Category: Materials Science Authors: Sydney R Lamerand, Anvita Anumolu, Ridhima Jain, Skyy Steber, Ronit Deshpande, Bradley K Taylor Source Type: research
The Efficacy of Phenol-Glucose-Glycerin Mixtures as a Prolotherapy Proliferative Substance on Fibroblast Tissue Culture
The number of Americans living with osteoarthritis today is estimated to be around 63 million. As the U.S. population ages, that number is projected to be as high as 78 million by 2040. Prolotherapy has served as a potential therapeutic that is both an alternative to joint replacement and more financially feasible compared to bio-injectables. However, significant gaps remain in our understanding of its molecular mechanisms and safety. While dextrose has become an increasingly popular prolotherapy substance, a cocktail composed of Phenol-glucose-glycerin (P2G) has also been historically used. (Source: The Journal of Pain)
Source: The Journal of Pain - April 1, 2024 Category: Materials Science Authors: Peter Sells, Allen Vayster, Amy Hinkelman, Thomas Motyka, Adam Foster, Bethany Harding, Sarah Fox Source Type: research
The Persistence Of Rodent Mechanical Hypersensitivity Following Chronic Constriction Injury From Chronic Early-Life Stress
Early-life environment is increasingly implicated as a risk factor for chronic pain. We evaluate whether early intervention of standard maternal nurturement could reverse chronic early-life stress (CES)-induced mechanical hypersensitivity. We used limited bedding to invoke CES in offspring of rats from postnatal day (PND)2-9. From PND10-weaning, litters were transferred to standard cages, and offspring from half the CES-litters were housed with dams subjected to only standard conditions (fostered). (Source: The Journal of Pain)
Source: The Journal of Pain - April 1, 2024 Category: Materials Science Authors: Kayleigh A. Rodriguez, Mary Grace Bishop, Laura R. Osborn, Kimberly E. Stephens Source Type: research
