Sex differences in the orofacial antinociceptive effect of metformin and the role of transient receptor potential channels.

Metformin is classified as a biguanide and is used in the treatment of type 2 diabetes. It is used worldwide and has been investigated in drug repositioning. The present study aims to investigate whether there is sexual dimorphism in the orofacial antinociceptive effect of metformin and the participation of TRP channels.

Modulatory Processes in Craniofacial Pain States.

Pain is a common symptom associated with many disorders affecting the craniofacial tissues that include the teeth and their supporting structures, the jaw, face and tongue muscles, and the temporomandibular joint. Most acute craniofacial pain states are easily recognized and readily treated, but chronic craniofacial pain states (e.g.

Pain-sensorimotor interactions: New perspectives and a new model.

How pain and sensorimotor behavior interact has been the subject of research and debate for many decades. This article reviews theories bearing on pain-sensorimotor interactions and considers their strengths and limitations in the light of findings from experimental and clinical studies of pain-sensorimotor interactions in the spinal and craniofacial sensorimotor systems. A strength of recent theories is that they have incorporated concepts and features missing from earlier theories to account for the role of the sensory-discriminative, motivational-affective, and cognitive-evaluative dimensions of pain in pain-sensorimotor interactions.

Introduction and a brief historical overview of the International Association for the Study of Pain.

The mission of the International Association for the Study of Pain (IASP) is "to bring together scientists, clinicians, healthcare providers, and policymakers to stimulate and support the study of pain and to translate that knowledge into improved pain relief worldwide." The IASP will celebrate its 50th anniversary next year, and the series of articles published in this special issue of its flagship journal PAIN highlights the IASP's achievements over the past 5 decades. This article provides a brief historical overview of the IASP's 50-year journey, including the key "players," events, and initiatives leading to its formation and contributing to its progress.

Multiple regions of sensorimotor cortex encode bite force and gape.

The precise control of bite force and gape is vital for safe and effective breakdown and manipulation of food inside the oral cavity during feeding. Yet, the role of the orofacial sensorimotor cortex (OSMcx) in the control of bite force and gape is still largely unknown. The aim of this study was to elucidate how individual neurons and populations of neurons in multiple regions of OSMcx differentially encode bite force and static gape when subjects generated different levels of bite force at varying gapes.

Fifty years of development of neuroscientific insights into oro-facial pain and its control.

When the Journal of Oral Rehabilitation was established in 1973, there was very limited understanding of the mechanisms underlying neurally based functions, including those unique to the face, mouth and jaws (e.g. dental pain, taste, chewing, swallowing and salivation).

Descending serotonergic modulation from rostral ventromedial medulla to spinal trigeminal nucleus is involved in experimental occlusal interference-induced chronic orofacial hyperalgesia.

Background: Dental treatment associated with unadaptable occlusal alteration can cause chronic primary myofascial orofacial pain. The serotonin (5-HT) pathway from the rostral ventromedial medulla (RVM) exerts descending modulation on nociceptive transmission in the spinal trigeminal nucleus (Sp5) and facilitates chronic pain. The aim of this study was to investigate whether descending 5-HT modulation from the RVM to the Sp5 is involved in the maintenance of primary myofascial orofacial hyperalgesia after persistent experimental occlusal interference (PEOI) or after delayed removal of experimental occlusal interference (REOI).

Transient receptor potential channel involvement in antinociceptive effect of citral in orofacial acute and chronic pain models.

This study aimed to test for the possible antinociceptive effect of the naturally occurring terpene citral in rodent models of acute and chronic orofacial pain and to test for the possible involvement of transient receptor potential (TRP) channels in this effect. Acute nociceptive behavior was induced in one series of experiments by administering formalin, cinnamaldehyde, menthol or capsaicin to the upper lip. Nociceptive behavior was assessed by orofacial rubbing, and the effects of pre-treatment with citral (0.

Neuronal Activities in the Rostral Ventromedial Medulla Associated with Experimental Occlusal Interference-Induced Orofacial Hyperalgesia.

The imbalanced conditions of pronociceptive ON-cells and antinociceptive OFF-cells in the rostral ventromedial medulla (RVM) alter nociceptive transmission and play an important role in the development of chronic pain. This study aimed to explore the neuroplastic mechanisms of the RVM ON-cells and OFF-cells in a male rat model of experimental occlusal interference (EOI)-induced nociceptive behavior reflecting orofacial hyperalgesia and in modified models involving EOI removal at early and later stages. We recorded the mechanical head withdrawal thresholds, orofacial operant behaviors, and the activity of identified RVM ON-cells and OFF-cells in these rats.

Botulinum toxin promotes orofacial antinociception by modulating TRPV1 and NMDA receptors in adult zebrafish.

The aim of the study was to evaluate the possible involvement of transient receptor potential (TRP) channels, Acid-sensing ion channels (ASIC) and N-Methyl-D-aspartate receptor (NMDAR) in the orofacial antinociceptive behaviour effect of botulinum toxin type A (BoNT/A) in adult zebrafish. Initially, the open field test was performed to evaluate the effect of BoNT/A on the locomotor activity of zebrafish. Subsequently, the animals were pretreated with BoNT/A (0.

Chronic Orofacial Pain: Models, Mechanisms, and Genetic and Related Environmental Influences.

Chronic orofacial pain conditions can be particularly difficult to diagnose and treat because of their complexity and limited understanding of the mechanisms underlying their aetiology and pathogenesis. Furthermore, there is considerable variability between individuals in their susceptibility to risk factors predisposing them to the development and maintenance of chronic pain as well as in their expression of chronic pain features such as allodynia, hyperalgesia and extraterritorial sensory spread. The variability suggests that genetic as well as environmental factors may contribute to the development and maintenance of chronic orofacial pain.

Responses of neurons in rostral ventromedial medulla to nociceptive stimulation of craniofacial region and tail in rats.

The rostral ventromedial medulla (RVM) plays a key role in the endogenous modulation of nociceptive transmission in the central nervous system (CNS). The primary aim of this study was to examine whether the activities of RVM neurons were related to craniofacial nociceptive behaviour (jaw-motor response, JMR) as well as the tail-flick response (TF). The activities of RVM neurons and TF and JMR evoked by noxious heating of the tail or perioral skin were recorded simultaneously in lightly anaesthetized rats.

Astrocytes in the rostral ventromedial medulla contribute to the maintenance of oro-facial hyperalgesia induced by late removal of dental occlusal interference.

Background: Astrocytes in the rostral ventromedial medulla (RVM) contribute to descending pain modulation, but their role in oro-facial pain induced by persistent experimental dental occlusal interference (PEOI) or following EOI removal (REOI) is unknown.

Objective: To explore the involvement of RVM astrocytes in PEOI-induced oro-facial hyperalgesia or its maintenance following REOI.

Methods: Male rats were randomly assigned into five groups: sham-EOI, postoperative day 6 and 14 of PEOI (PEOI 6 d and PEOI 14 d), postoperative day 6 following REOI on day 3 (REOI 3 d) and postoperative day 14 following REOI on day 8 (REOI 8 d).

The Canadian Pain Society: A historical perspective.

This article reviews the major features and events that have characterized the 40-year history of the Canadian Pain Society/Société canadienne de la douleur, which is a chapter of the International Association for the Study of Pain (IASP). The review first describes its early formative years in the 1970s as eastern and western chapters of IASP and then its evolution as a Canada-wide chapter and society. Also highlighted is the formulation in this period of its purpose to foster pain research, education, and management and the many activities in which the Society has been engaged to reinforce this purpose over the ensuing decades.

Properties of heat-sensitive neurons in the premotor cortex of conscious monkeys.

To investigate neuronal activity involved in responses to noxious stimuli in conscious monkeys, the animals were subjected to a task that required them to detect a small change in facial skin temperature or light (second temperature: T2, second light: V2) relative to an initial condition (T1 or V1), and to detect changes in V2 along with a heat task. Recordings were obtained from 57 neurons in the ventral premotor cortex (PMv) during the heat or light detection task. T1 neurons and T2 neurons showed increased activity only during T1 or T2, and T1/T2 neurons were activated by both T1 and T2 stimuli.

Toll-Like Receptor 4 in the Rat Caudal Medulla Mediates Tooth Pulp Inflammatory Pain.

The aims of this study were to investigate if Toll-like receptor 4 (TLR4) is expressed in the medullary dorsal horn (MDH) and if medullary application of a TLR4 antagonist (lipopolysaccharides from , LPS-RS) can attenuate changes in nociceptive sensorimotor responses or TLR4 expression that might be evoked by mustard oil (MO) application to the right maxillary first molar tooth pulp. Of 41 adult male Sprague-Dawley rats used in the study, 23 received intrathecal application of the TLR4 antagonist LPS-RS (25 μg/10 μl; LPS-RS group) or isotonic saline (10 μl; vehicle control group) 10 min before pulpal application of MO (95%; 0.2 μl).

NMDA and purinergic processes modulate neck muscle activity evoked by noxious stimulation of dura.

Background: Adenosine triphosphate (ATP) and glutamate are associated with some headache conditions, and purinergic (P2X) and glutamatergic N-methyl-D-aspartate (NMDA) receptor-related processes in the medulla can modulate the effects of trigeminal nociceptive afferent inputs into the brainstem on craniofacial sensorimotor circuits. This study aimed to test whether neck muscle activity can be induced in rats by noxious stimulation of the frontal dura or superior sagittal sinus that involves P2X or NMDA receptor-dependent mechanisms.

Methods: While electromyographic activities of neck and craniofacial muscles were being recorded in anesthetized rats (n = 46), the inflammatory irritant mustard oil (0.

Dental sleep medicine: Time to incorporate sleep apnoea education in the dental curriculum.

Dental sleep medicine is a discipline that includes conditions such as sleep breathing disorders (eg snoring and sleep apnoea), sleep bruxism, orofacial pain and sleep-related complaints, and to some extent gastro-oesophageal reflux disorder and/or insomnia. Obstructive sleep apnoea (OSA) is a life-threatening condition that dentists need to identify and manage when indicated in order to increase patient well-being and to be taken in consideration in the dental curriculum. The main objective of this paper is to highlight the relevance of dental sleep medicine in the context of dental education, and to discuss potential educational content for integration in the dental curriculum with a focus on OSA, a condition that is not yet integrated in many dental training curricula around the world.

Orofacial Antinociceptive Effect of Nifedipine in Rodents Is Mediated by TRPM3, TRPA1, and NMDA Processes.

Aims: To test for the possible antinociceptive effect of nifedipine in rodent models of acute and chronic neuropathic orofacial pain and the possible involvement of TRP- and NMDA-related processes in this effect.

Methods: Acute nociceptive behavior was induced by administering formalin, cinnamaldehyde, glutamate, capsaicin, or acidified saline to the upper lip or hypertonic saline to the cornea of Swiss mice. Acute nociceptive behavior was also induced by formalin injected into the TMJ or mustard oil injected into the masseter muscle of Wistar rats.

Combination of jaw and tongue movement training influences neuroplasticity of corticomotor pathways in humans.

Since humans in daily life perform multiple motor behaviors that often involve the simultaneous activation of both jaw and tongue muscles, it is essential to understand the effects of combined orofacial sensorimotor tasks on plasticity in corticomotor pathways. Moreover, to establish novel rehabilitation programs for patients, it is important to clarify the possible interrelationships in corticomotor excitability between jaw and tongue motor control. The aim of this study was to examine the effect of a combination of a repetitive tooth bite task (TBT) and a repetitive tongue lift task (TLT) on corticomotor excitability of the tongue and jaw muscles as assessed by transcranial magnetic stimulation (TMS).

Can you be too old for oral implants? An update on ageing and plasticity in the oro-facial sensorimotor system.

This review focuses on the capacity of the brain for plasticity and the utility and efficacy of oral implants in helping to restore oro-facial sensorimotor functions, especially in elderly patients. The review first outlines the components of the oro-facial sensorimotor system which encompasses both oro-facial tissues and a number of brain regions. One such region is the sensorimotor cortex that controls the activity of the numerous oro-facial skeletal muscles.

Tooth extraction and subsequent dental implant placement in Sprague-Dawley rats induce differential changes in anterior digastric myofibre size and myosin heavy chain isoform expression.

Objective: to determine if tooth loss and dental implant placement in rats induce changes in the morphological and histochemical features of the Anterior Digastric muscle.

Design: Adult male Sprague-Dawley rats had their right maxillary molar teeth extracted. 'Extraction-1' and 'Extraction-2 groups were sacrificed, respectively, 4 or 8 weeks later, and an Implant group had an implant placement 2 weeks after the molar extraction, and rats were sacrificed 3 weeks later (n = 4/group).

Face sensorimotor cortex undergoes neuroplastic changes in a rat model of trigeminal neuropathic pain.

Trigeminal nerve injury can result in neuropathic pain behavior and alterations in motor function, but it is unclear if such injury produces neuroplastic alterations in face sensorimotor cortex that could contribute to the alterations in motor function. Therefore, this study aimed to determine if trigeminal nerve injury in a rat neuropathic pain model induces neuroplastic changes in jaw and tongue motor representations in face sensorimotor cortex in association with facial nociceptive behavior. Right infraorbital nerve transection was performed in adult male Sprague-Dawley rats; sham-operated rats served as controls.