Paul L Durham

Missouri State University | MSU · Department of Biology

Purpose of Review To provide information from preclinical and clinical studies on the biological activity and health benefits of dietary inclusion of nutraceuticals as a safe, effective, non-pharmacological approach for the treatment of migraine. Recent Findings There is emerging evidence of the therapeutic benefit of nutraceuticals to inhibit oxi...

Background: Migraine is associated with neuroimaging differences in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). However, it is unknown if migraine-related disability (MRD) or if calcitonin gene-related peptide (CGRP), a vasoactive peptide important in migraine pathology, have radiographic i...

The trigeminal ganglion is implicated in the underlying pathology of migraine and temporomandibular joint disorders (TMD), which are orofacial pain conditions involving peripheral and central sensitization. The neuropeptide calcitonin gene-related peptide (CGRP) is synthesized in some trigeminal ganglion neurons, and its release promotes inflammati...

Migraine is associated with peripheral and central sensitization of the trigeminal system and dysfunction of descending pain modulation pathways. Recently, dietary inclusion of grape seed extract (GSE) was shown to inhibit mechanical nociception in a preclinical model of chronic temporomandibular joint disorder, a condition often comorbid with migr...

Migraine involves brain hypersensitivity with episodic dysfunction triggered by behavioral or physiological stressors. During an acute migraine attack the trigeminal nerve is activated (peripheral sensitization). This leads to central sensitization with activation of the central pathways including the trigeminal nucleus caudalis, the trigemino-thal...

Background: Temporomandibular joint disorder is a prevalent orofacial pain condition involving sensitization and activation of trigeminal nociceptive neurons. Dietary supplementation with a proanthocyanin-enriched grape seed extract (GSE) was found to inhibit trigeminal nociception in a chronic TMD model. In this study, the cellular mechanisms by w...

Introduction: Chronic headache conditions are characterized by persistent sensitization of the trigeminal system, which involves dysfunction of descending pain modulation. We previously reported that noninvasive vagus nerve stimulation (nVNS) inhibits trigeminal nociception in models of episodic migraine through a mechanism involving enhanced sero...

Background: The risk factors neck muscle tension, prolonged jaw opening, and female gender are associated with developing temporomandibular disorders (TMD), which are characterized by persistent sensitization of trigeminal neurons and enhanced pain signaling. Dietary supplementation with a grape seed extract (GSE) can modulate expression of protei...

Several biologically active bivalent Pd and Pt complexes with two structurally similar cyanoxime ligands abbreviated as H(DECO): 2-oximino-2-cyano-N,N′-diethylacetamide, and H(PyrCO): 2-oximino-2-cyan-N-pyrrolidine acetamide were synthesized and characterized using spectroscopic methods, thermal analysis and X-ray crystallography. Structures reveal...

Early life stress is a risk factor for development of migraine, a prevalent painful neurological disease characterized by sensitization and activation of trigeminal neurons. Secondary early life stress was previously shown to cause increased expression of neuronal proteins implicated in peripheral and central sensitization. Recently, dietary supple...

Migraine is a prevalent neurological disease that is characterized by unpredictable episodic attacks of intense head pain. The underlying pathology involves sensitization and activation of the trigeminal system. Although non-invasive vagus nerve stimulation (nVNS) is recommended for the treatment of migraine, the abortive mechanism of action is not...

Aims: To evaluate the modulatory effect of plant extracts on the expression of mitogen-activated protein kinase phosphatase-1 (MKP-1) and the protein kinases PERK and P-p38 in primary cultures of trigeminal ganglion from Sprague Dawley rats. Study Design: In vitro analysis of methanol extracts on proteins implicated in inflammation and pain signali...

Aims: To test a commercially available enriched chicken bone broth (ECBB) product for its potential anti-inflammatory properties and to evaluate its ability to reduce nociception and expression of protein kinase A (PKA) in a clinically relevant model of temporomandibular disorder (TMD) caused by prolonged jaw opening in rats. Methods: The potent...

The pathology of migraine, a common neurological disease, involves sensitization and activation of trigeminal nociceptive neurons to promote hyperalgesia and allodynia during an attack. Migraineurs often exhibit characteristics of a hyperexcitable or hypervigilant nervous system. One of the primary reported risk factors for development of a hyperex...

Introduction:. Although neck muscle tension is considered a risk factor for migraine, pungent odors can act as a trigger to initiate an attack in sensitized individuals. Although noninvasive vagus nerve stimulation (nVNS) is now an approved treatment for chronic migraine, how it functions to inhibit trigeminal nociception in an episodic migraine mo...

Aims: To investigate cellular changes in the spinal trigeminal nucleus (STN) and trigeminal ganglion (TG) associated with trigeminal nociception mediated by inflammation in the temporomandibular joint (TMJ). Methods: Male Sprague-Dawley rats (n = 86) were utilized to investigate cellular and behavioral responses to prolonged TMJ inflammation cau...

Objectives: To investigate and discuss the effects of cocoa on orofacial pain. Setting and sample population: The Department of Orthodontics at the University of Florida (UF). Male and female hairless rats (N=20/group) were tested. Materials and methods: Rats were tested using the Orofacial Pain Assessment Device (OPAD) before and after changi...

Objective: Elevated levels of tumor necrosis factor- alpha (TNF-α) in the capsule of the temporomandibular joint (TMJ) are implicated in the underlying pathology of temporomandibular disorders (TMD). TMD are a group of conditions that result in pain in the TMJ and/or muscles of mastication, and are associated with significant social and economic b...

Orofacial pain conditions including temporomandibular disorder (TMD) and migraine are characterized by peripheral and central sensitization of trigeminal nociceptive neurons. The goal of this study was to investigate the role of calcitonin gene-related peptide (CGRP) in promoting bidirectional signaling within the trigeminal system to mediate sensi...

The neuropeptide calcitonin gene-related peptide (CGRP) is implicated in the underlying pathology of migraine by promoting the development of a sensitized state of primary and secondary nociceptive neurons. The ability of CGRP to initiate and maintain peripheral and central sensitization is mediated by modulation of neuronal, glial, and immune cell...

Objective The focus of this study was to characterize shifts in the rodent gut microbiota that occur as a result from the oral administration of the commercial chicken broth formulation AAC1. Background There is emerging evidence of the importance of maintaining a healthy gut microbiome. Changes in the ratio of the phylum Bacteroidetes to the phyl...

Objective To investigate the differences in the level or activity of biochemical molecules contained in enriched AAC1 and traditional homemade chicken broth that are implicated in improving and maintaining good joint health. Background Chicken broth is a complex mixture containing extractives obtained from cooking of chicken parts or whole chicken...

Objective The goal of this study was to determine if the dietary inclusion of the commercially available chicken broth AAC1 could repress nocifensive behaviors and PKA expression associated with a clinically relevant model of temporomandibular joint (TMJ) disorder caused by prolonged jaw opening. Background Routine dental visits for molar extracti...

Aims: To test the hypothesis that prolonged jaw opening, as can occur during routine dental procedures, increases nociceptive sensitivity of the masseter muscle and increases cytokine expression. Methods: Sprague-Dawley rats were used to investigate behavioral and cellular changes in response to prolonged jaw opening. A surgical retractor was pl...

Chronic migraine (CM) is a relatively new medical diagnosis that is identified as 15 or more days of headache per month. Being the most common neurological condition for which individuals seek medical consultation, primary headache disorders are often misdiagnosed and mismanaged. Even though migraine is considered to be the result of a genetic pred...

Increased utilization of inorganic silver as an adjunctive to many medical devices has raised concerns of emergent silver resistance in clinical bacteria. Although the molecular basis for silver-resistance has been previously characterized, to date, significant phenotypic expression of these genes in clinical settings has yet to be observed. Here w...

Eggshell membrane (ESM) has been shown to contain naturally occurring bioactive components, and biological activities such as reducing proinflammatory cytokines, liver fibrosis, and joint pain in osteoarthritis sufferers have also been reported for ESM matrix as a whole. Nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-κB) is a si...

Purpose Eggshell membrane (ESM) has been shown to contain naturally occurring bioactive components, and biological activities such as reducing proinflammatory cytokines, liver fibrosis, and joint pain in osteoarthritis sufferers have also been reported for ESM matrix as a whole. Nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-κB)...

Pain patients who are nicotine dependent report a significantly increased incidence and severity of pain intensity. The goal of this study was to determine the effects of prolonged nicotine administration on inflammatory proteins implicated in the development of peripheral and central sensitization of the trigeminal system. Behavioral, immunohistoc...

Objectives This study was conducted to identify the types of functional voltage-gated calcium channels expressed by the neuronal-like human parafollicular (CA77) cancer cell line. Methods CA77 cells were grown in culture and the expression of functional calcium channels studied using Fura-2 am during live cell imaging to measure changes in intrace...

To establish the substrate specificity of the thioglucoside glucohydrolase myrosinase (EC 3.2.3.1), this enzyme was purified to homogeneity from light-grown cress (Lepidium sativum L.) seedlings by Sephadex gel filtration. Red Dye and anion exchange (FPLC Mono Q) chro­matography, and preparative isoelectric focusing. Hydrolytic activity was shown t...

Sensitization and activation of trigeminal nociceptors is implicated in prevalent and debilitating orofacial pain conditions including temporomandibular joint (TMJ) disorders. Orexins are excitatory neuropeptides that function to regulate many physiological processes and are reported to modulate nociception. To determine the role of orexins in an i...

To determine if baseline/interictal saliva calcitonin gene-related peptide (CGRP) levels would be lower in subjects with chronic migraine receiving onabotulinumtoxinA compared with those receiving saline. CGRP is considered central to the pathogenesis of episodic migraine, but its relationship to chronic migraine is less understood. Onabotulinumtox...

The focus of this review is to review potential diagnostic and therapeutic biomarkers associated with migraine. Migraine headache is a common disease that affects millions of individuals worldwide. Although well-accepted diagnostic criteria exist for migraine, it is still a complex disorder that remains both underdiagnosed and misdiagnosed. The cau...

Scope: Central sensitization is implicated in the pathology of temporomandibular joint disorder and other types of orofacial pain. We investigated the effects of dietary cocoa on expression of proteins involved in the development of central sensitization in the spinal trigeminal nucleus (STN) in response to inflammatory stimulation of trigeminal n...

Objective/background: The goal of this study was to better understand the cellular mechanisms involved in proton stimulation of calcitonin gene-related peptide (CGRP) secretion from cultured trigeminal neurons by investigating the effects of 2 antimigraine therapies, onabotulinumtoxinA and rizatriptan. Stimulated CGRP release from peripheral and c...

Aims: To test the reliability and validity of a novel rat-holding device designed to be used in conjunction with the plantar test apparatus for studying nocifensive behavioral responses in an established model of temporomandibular joint (TMJ) pathology. Methods: Thirty-five young adult male Sprague-Dawley rats were used. Withdrawal latencies in...

An inexpensive and rapid bioassay using adult red flour beetles was developed for use in assessing the decontamination of environments containing organophosphates and related chemicals. A decontamination protocol was developed which demonstrated that 2 to 3 applications of 5% bleach solution were required to obtain nearly complete decontamination o...

In recent years, many non-classical groups of Pt-compounds, including complexes with the trans-geometry, polynuclear complexes, and compounds with a variety of extended heterocyclic ligands, were obtained and studied. Part 1 of this work contains the results of our X-ray crystallographic and computational studies of a group of recently-discovered c...

A controlled drug release system based on biocompatible and electroactive polymers (EAP) was built to promote wound healing. Negatively-charged as well as positively-charged drugs were loaded into EAP systems through electro-polymerization in the presence of prepolymer and supporting electrolytes. Release was precisely controlled by applying an ele...

The goal of this study was to use protein array analysis to investigate temporal regulation of stimulated cytokine expression in trigeminal ganglia and the spinal trigeminal nucleus in response to co-treatment of sumatriptan and naproxen sodium or individual drug. Activation of neurons and glia in trigeminal ganglia and the spinal trigeminal nucleu...

Calcitonin gene-related peptide (CGRP), a neuropeptide released from trigeminal nerves, is implicated in the underlying pathology of temporomandibular joint disorder (TMD). Elevated levels of CGRP in the joint capsule correlate with inflammation and pain. CGRP mediates neurogenic inflammation in peripheral tissues by increasing blood flow, recruiti...

OnabotulinumtoxinA has recently been approved by regulatory agencies in the UK and United States for treatment of chronic migraine based on data generated from the PREEMPT studies. As such, onabotulinumtoxinA is the only prophylactic therapy specifically approved for chronic migraine. Most headache clinicians would agree that acute episodic migrain...

Previously published findings from our laboratory have shown that cocoa extract inhibits activation of trigeminal neurons in culture and in animals fed a cocoa enriched diet. Activation of trigeminal neurons is implicated in the underlying pathology of migraine, rhinosinusitis, and TMJ or jaw joint disorders. Within trigeminal neurons, proteins kno...

Intranasal noninhaled delivery of carbon dioxide (CO₂) is efficacious in the symptomatic treatment of seasonal allergic rhinitis. The goal of this study was to determine whether and how 100% CO₂ inhibits mast cell degranulation, thereby possibly contributing to the reduction of symptoms in seasonal allergic rhinitis.   Peritoneal mast cells isolate...

Headache treatment has been based primarily on experiences with non-specific drugs such as analgesics, non-steroidal anti-inflammatory drugs, or drugs that were originally developed to treat other diseases, such as beta-blockers and anticonvulsant medications. A better understanding of the basic pathophysiological mechanisms of migraine and other t...

Inflammation and pain associated with temporomandibular joint disorder, a chronic disease that affects 15% of the adult population, involves activation of trigeminal ganglion nerves and development of peripheral and central sensitization. Natural products represent an underutilized resource in the pursuit of safe and effective ways to treat chronic...

Cell bodies of trigeminal nerves, which are located in the trigeminal ganglion, are completely surrounded by satellite glial cells and together form a functional unit that regulates neuronal excitability. The goals of this study were to investigate the cellular organization of the rat trigeminal ganglia during postnatal development and correlate th...

To investigate the mechanism by which adenosine triphosphate (ATP) causes sensitization of trigeminal neurons and how dihydroergotamine (DHE) represses this modulatory effect. Dihydroergotamine is an effective treatment of migraine. The cellular mechanisms of action of DHE in treating migraine attacks remain unclear. In this study, neonatal rat tri...

Based on preclinical and clinical studies, the neuropeptide calcitonin gene-related peptide (CGRP) is proposed to play a central role in the underlying pathology of migraine. CGRP and its receptor are widely expressed in both the peripheral and central nervous systems by multiple cell types involved in the regulation of inflammatory and nociceptive...

Pain in the head and face, which can be very severe and debilitating, often involves activation of trigeminal ganglion nerves. The craniofacial symptoms can manifest as acute or transient conditions such as toothaches and headaches, or can transform into more chronic conditions such as migraine, rhinosinusitis, temporomandibular joint (TMJ) disorde...

To measure prostaglandin levels in the saliva of individuals during menstrual migraine associated with dysmenorrhea (MMaD) and in response to treatment with a single tablet combination of sumatriptan succinate and naproxen sodium. Prostaglandins are thought to play a role in MMaD as elevated serum prostaglandin levels have been reported during atta...

Calcitonin gene-related peptide (CGRP) is a multifunctional neuropeptide implicated in inflammatory diseases involving trigeminal ganglion nerve activation. Within trigeminal ganglia, satellite glia and Schwann cells are found in close association with neuronal cell bodies and fibers, respectively, and are known to express functional CGRP receptors...

Activation of trigeminal nerves and release of neuropeptides that promote inflammation are implicated in the underlying pathology of migraine and temporomandibular joint (TMJ) disorders. The overall response of trigeminal nerves to peripheral inflammatory stimuli involves a balance between enzymes that promote inflammation, kinases, and those that...

Migraine is a neurovascular disorder characterized by recurrent episodic headaches, and is caused by abnormal processing of sensory information due to peripheral and/or central sensitization. The exact pathophysiological mechanism underlying migraine is not fully understood; however, cortical spreading depression (CSD) is thought to provide the bas...

(1) To measure calcitonin gene-related peptide (CGRP) levels in the saliva of individuals with migraine during the premonitory period, mild headache, moderate to severe headache, and post-resolution phases as compared with baseline (interictal) CGRP levels. (2) To correlate response to rizatriptan administered during moderate headache with levels o...