A novel computerized system for thermal stimulation of tooth in ferrets

A dual thermal and electrical stimulator was developed to examine the central pathways that transmit noxious stimuli for intact dentition. This system allows computer-controlled stimulation of the canines of ferrets with either noxious heat or electrical stimuli. A set of in vitro studies demonstrated that the application of thermal stimuli to an intact tooth can produce pulpal temperatures above 43°C, which is perceived as a painful stimulus in humans. In a set of in vivo studies, it was demonstrated that heating an intact tooth at temperatures of at least 40°C, excited trigeminal brainstem neurons. Only 15% of the neurons activated by electrical stimulation responded to noxious heat applied to the canine. Eight of the 23 neurons were classified as nociceptive specific neurons and responded only to noxious stimulation of their cutaneous receptive fields. Fifteen of the 23 neurons were classified as wide dynamic range neurons and responded to both noxious and non-noxious stimulation applied to their cutaneous receptive fields. This new device can accurately deliver both thermal and electrical stimuli to an intact tooth, which allows an evaluation of the central neural circuits that respond to noxious stimulation of the dentition

Changes in pain from a repetitive thermal stimulus: The roles of adaptation and sensitization

This study examined processes that contribute to the changing painfulness of a repeatedly presented thermal (heat) stimulus. The 3-s pulses were presented to the side of the hand at a rate of 4/min, too slow to engage wind-up. Over the course of 32 trials, pain intensity (measured by verbal report on a 0–100 scale) first declined and then (in most cases) rose again, indicating adaptation and sensitization, respectively. The magnitude of adaptation grew across a series of three runs, indicating that adaptation has a slow as well as a fast component. The rate of sensitization depended on stimulus temperature, but not on subjective pain intensity; this result implies that sensitization takes place at an early processing stage. Adaptation and sensitization were comparable in participants with fibromyalgia (FM), temporomandibular disorders (TMD), and in healthy controls (HC), indicating these processes occur before the perceptual amplification that characterizes FM and TMD. The ability of vibration to reduce pain has previously been shown to involve segmental inhibition; the finding in the present study that vibratory gating of pain is significantly (inversely) related to the rate of sensitization suggests that the latter also reflects segmental processes. Several lines of evidence thus point to the conclusion that adaptation and sensitization occur at early stages of sensory information processing

Performance Characteristics of Novel Instruments for Mucosal and Pelvic Muscle Pain Sensitivity Assessment

Background: Despite considerable advances in our understanding of mechanisms operative in persistent pain states, little is known about the pathophysiology of chronic pain in gynecology. Advances in the field have been critically impaired by lack of methodology and conceptual models to investigate the joint and independent contribution of pelvic muscle and mucosa to persistent pain. Using provoked vestibulodynia (PVD) as our model, we set to develop novel instruments for assessing mucosal and muscle pain sensitivity. PVD is a clinical diagnosis rendered after excluding other conditions and is diagnosed when genital palpation of vulvar mucosa with a cotton swab is painful. PVD is a heterogeneous diagnosis. Other conditions associated with PVD, such as myofasical dysfunction (i.e., difficulty with muscle relaxation and pain), psychological distress (i.e., anxiety and somatization), and nongenital somatic pain in response to thermal and mechanical stimuli, are thought to be secondary to a persistent pain state. PVD is clinically subdivided into two subgroups (primary and secondary) based on onset of pain. Primary VVS is defined when the onset of pain was with the first act of intercourse or tampon use. Secondary VVS is characterized by a pain free interval prior to the onset of pain. We hypothesized that the experience of pain in the primary subgroup of women with PVD may be driven by pelvic muscle (akin to orofacial pain), with the mucosa acting as a referral site

Overlapping Chronic Pain Conditions: Implications for Diagnosis and Classification

AbstractThere is increasing recognition that many if not most common chronic pain conditions are heterogeneous with a high degree of overlap or coprevalence of other common pain conditions along with influences from biopsychosocial factors. At present, very little attention is given to the high degree of overlap of many common pain conditions when recruiting for clinical trials. As such, many if not most patients enrolled into clinical studies are not representative of most chronic pain patients. The failure to account for the heterogeneous and overlapping nature of most common pain conditions may result in treatment responses of small effect size when these treatments are administered to patients with chronic overlapping pain conditions (COPCs) represented in the general population. In this brief review we describe the concept of COPCs and the putative mechanisms underlying COPCs. Finally, we present a series of recommendations that will advance our understanding of COPCs.PerspectiveThis brief review describes the concept of COPCs. A mechanism-based heuristic model is presented and current knowledge and evidence for COPCs are presented. Finally, a set of recommendations is provided to advance our understanding of COPCs

Alternative Splicing of G Protein–Coupled Receptors: Relevance to Pain Management

Drugs that target G-protein coupled receptors (GPCRs) represent the primary treatment strategy for patients with acute and chronic pain; however, there is substantial individual variability in both the efficacy and adverse side effects associated with these drugs. Variability in drug responses is, in part, due to individuals’ diversity in alternative splicing of pain-relevant GPCRs. GPCR alternative splice variants often exhibit distinct tissue distribution patterns, drug binding properties, and signaling characteristics that may impact disease pathology as well as the size and direction of analgesic effects. Here, we review the importance of GPCRs and their known splice variants to the management of pain

Widespread somatosensory sensitivity in naturally occurring canine model of osteoarthritis

Osteoarthritis (OA)-associated pain is a leading cause of disability. Central sensitization (CS), as a result of OA, is recognized as an important facet of human patients' chronic pain and has been measured in people using quantitative sensory testing (QST) testing. The spontaneous canine OA model has been suggested as a good translational model, but CS has not been explored in this model. In this study, QST was performed on dogs with and without spontaneous hip or stifle OA to determine whether OA is associated with CS in this model. Mechanical (von Frey and blunt pressure) and thermal (hot and cold) sensory thresholds obtained in dogs with chronic OA-associated pain (n = 31) were compared with those of normal dogs (n = 23). Dogs were phenotyped and joint-pain scored, and testing was performed at the OA-affected joint, cranial tibial muscle, and dorsal metatarsal region. QST summary data were evaluated using mixed-effect models to understand the influence of OA status and covariates, and dogs with OA and control dogs were compared. The presence of OA was strongly associated with hyperalgesia across all QST modalities at the index joint, cranial tibial muscle, and metatarsal site. Mechanical QST scores were significantly moderately negatively correlated with total joint-pain scores. The spontaneous canine OA model is associated with somatosensory sensitivity, likely indicative of CS. These data further validate the canine spontaneous OA model as an appropriate model of the human OA pain condition

Psychophysical responses to a speech stressor: Correlation of plasma beta-endorphin levels at rest and after psychological stress with thermally measured pain threshold in patients with coronary artery disease

OBJECTIVES: We tested the hypothesis that psychological stress alters plasma levels of opioid peptides and that these plasma levels are related to pain perception in patients with coronary artery disease. BACKGROUND: Public speaking psychological stress has previously been shown to be associated with silent ischemia. METHODS: After instrumentation and a 30-min rest period, venous blood samples for beta-endorphin were obtained before and immediately after psychological stress in 20 patients with coronary artery disease. Pain threshold was then assessed using a thermal probe technique at baseline and immediately after stress. Patients gave three brief speeches lasting a total of 15 min about real-life hassle situations. RESULTS: Psychological stress significantly increases plasma beta-endorphin levels (4.3 +/- 0.9 pmol/liter [mean +/- SE] at rest to 8.3 +/- 2 pmol/liter after stress, p < 0.05). There was a significant positive correlation between pain threshold and beta-endorphin levels after stress (r = 0.577, p = 0.008). This significant positive correlation was still present while rest blood pressure and change in blood pressure during stress were controlled for by analysis of covariance techniques. CONCLUSIONS: In patients with coronary artery disease and exercise-induced ischemia, public speaking produces psychological stress manifested by increased cardiovascular reactivity and causes an increase in plasma beta-endorphin levels that is significantly correlated with pain thresholds. These findings may explain the predominance of silent ischemia during psychological stress in patients with coronary artery disease

Prevalence of Orofacial Pain Among Women with Vulvodynia: Prospective Two Year Follow-Up Study

Background: Vulvar Vestibulitis (VVS) is the most common cause of vulvodynia in reproductive age women, affecting up to 15% of the general female population. Women with VVS have pain with intercourse, and sensitivity to touch on genital contact. Psychological characteristics such as anxiety and somatization are also common in the population. Evidence supports VVS as a complex pain disorder, akin to idiopathic musculoskeletal pain conditions, such as temporomandibular disorder, the most common form of orofacial pain (OFP). We have previously found that OFP was a common co-morbidity among women with VVS. Higher levels of anxiety, somatization, and psychological distress were found among women with VVS and OFP, than among those women with VVS and no OFP. Objective: The primary objective of this study was to assess the stability of our original findings and investigate the change in OFP symptoms over a 2 yr period among women with vulvar vestibulitis