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., temporomandibular disorders [TMD], trigeminal neuropathies, and some headaches) may be especially challenging to manage successfully. This chapter provides an overview of the processes that underlie craniofacial pain, with a focus on the pain-modulatory mechanisms operating in craniofacial tissues and in the central nervous system (CNS), including the role of endogenous chemical processes such as those involving opioids. The chapter outlines in particular findings from preclinical studies that have provided substantial information about the neural as well as nonneural (e.g., glial) processes involved in the initiation, transmission, and modulation of nociceptive signals in the trigeminal system, and also draws attention to their clinical correlates. The increased understanding gained from these preclinical studies of how nociceptive signals can be modulated will contribute to improvements in presently available therapeutic approaches to manage craniofacial pain as well as to the development of novel analgesic approaches.

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. Findings acquired since the formulation of these recent theories indicate that additional features need to be considered to provide a more comprehensive conceptualization of pain-sensorimotor interactions. These features include biopsychosocial influences that range from biological factors such as genetics and epigenetics to psychological factors and social factors encompassing environmental and cultural influences. Also needing consideration is a mechanistic framework that includes other biological factors reflecting nociceptive processes and glioplastic and neuroplastic changes in sensorimotor and related brain and spinal cord circuits in acute or chronic pain conditions. The literature reviewed and the limitations of previous theories bearing on pain-sensorimotor interactions have led us to provide new perspectives on these interactions, and this has prompted our development of a new concept, the Theory of Pain-Sensorimotor Interactions (TOPSMI) that we suggest gives a more comprehensive framework to consider the interactions and their complexity. This theory states that pain is associated with plastic changes in the central nervous system (CNS) that lead to an activation pattern of motor units that contributes to the individual's adaptive sensorimotor behavior. This activation pattern takes account of the biological, psychological, and social influences on the musculoskeletal tissues involved in sensorimotor behavior and on the plastic changes and the experience of pain in that individual. The pattern is normally optimized in terms of biomechanical advantage and metabolic cost related to the features of the individual's musculoskeletal tissues and aims to minimize pain and any associated sensorimotor changes, and thereby maintain homeostasis. However, adverse biopsychosocial factors and their interactions may result in plastic CNS changes leading to less optimal, even maladaptive, sensorimotor changes producing motor unit activation patterns associated with the development of further pain. This more comprehensive theory points towards customized treatment strategies, in line with the management approaches to pain proposed in the biopsychosocial model of pain.

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

ABSTRACT: 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. It complements the other articles outlining the contributions that the IASP has made and likely will continue to make to advances in pain education, research, management and advocacy, and its value to the IASP members.

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 (Macaca mulatta) generated different levels of bite force at varying gapes. We examined neuronal activity recorded simultaneously from three microelectrode arrays implanted chronically in the primary motor (MIo), primary somatosensory (SIo), and cortical masticatory (CMA) areas of OSMcx. We used generalized linear models to evaluate encoding properties of individual neurons and utilized dimensionality reduction techniques to decompose population activity into components related to specific task parameters. Individual neurons encoded bite force more strongly than gape in all three OSMCx areas although bite force was a better predictor of spiking activity in MIo vs. SIo. Population activity differentiated between levels of bite force and gape while preserving task-independent temporal modulation across the behavioral trial. While activation patterns of neuronal populations were comparable across OSMCx areas, the total variance explained by task parameters was context-dependent and differed across areas. These findings suggest that the cortical control of static gape during biting may rely on computations at the population level whereas the strong encoding of bite force at the individual neuron level allows for the precise and rapid control of bite force.

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). Since that time, technological and other advances have led to new insights into the structure, connectivity and function of cranial nerves and areas of the central nervous system (CNS) involved in oro-facial functions and disorders or related functions (e.g. cognition, emotion, stress, consciousness, sleep, learning and memory). This review focuses on the advances in understanding of the neural basis of oro-facial pain and its control over the past five decades. The review first briefly considers how oro-facial pain conditions are now classified, diagnosed and managed. It then outlines novel insights that have been gained over this period through neuroscience research into the neural basis of these oro-facial pain conditions and the clinical relevance to these insights to the diagnosis and management of these conditions. The review also identifies promising research directions and gaps in knowledge that still need to be addressed to improve the understanding, diagnosis and management of oro-facial pain conditions.

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). METHODS: Expressions of 5-HT3A and 5-HT3B receptor subtypes in the Sp5 were assessed by immunofluorescence staining and Western blotting. The release and metabolism of 5-HT in the Sp5 were measured by high-performance liquid chromatography. Changes in the pain behavior of these rats were examined after specific pharmacologic antagonism of the 5-HT3 receptor, chemogenetic manipulation of the RVM 5-HT neurons, or selective down-regulation of 5-HT synthesis in the RVM. RESULTS: Upregulation of the 5-HT3B receptor subtype in the Sp5 was found in REOI and PEOI rats. The concentration of 5-HT in Sp5 increased significantly only in REOI rats. Intrathecal administration of Y-25130 (a selective 5-HT3 receptor antagonist) dose-dependently reversed the hyperalgesia in REOI rats but only transiently reversed the hyperalgesia in PEOI rats. Chemogenetic inhibition of the RVM 5-HT neurons reversed the hyperalgesia in REOI rats; selective down-regulation of 5-HT in advance also prevented the development of hyperalgesia in REOI rats; the above two manipulations did not affect the hyperalgesia in PEOI rats. However, chemogenetic activation of the RVM 5-HT neurons exacerbated the hyperalgesia both in REOI and PEOI rats. CONCLUSIONS: These results provide several lines of evidence that the descending pathway from 5-HT neurons in the RVM to 5-HT3 receptors in the Sp5, plays an important role in facilitating the maintained orofacial hyperalgesia after delayed EOI removal, but has a limited role in that after persistent EOI.

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 (HWTs), orofacial operant behaviors, and the activity of identified RVM ON-cells and OFF-cells in these rats. EOI-induced orofacial hyperalgesia could be relieved by EOI removal around postoperative day 3; this effect could be inhibited by intra-RVM microinjection of the kappa-opioid receptor agonist U-69593. EOI removal around postoperative day 8 did not relieve the orofacial hyperalgesia which could however be reversed by intra-RVM microinjection of the NK-1 receptor antagonist L-733060. The activity of ON-cells and OFF-cells did not change during both the initial 3 and 6 days of EOI. When EOI was removed on postoperative day 3, OFF-cell responses decreased, contributing to the reversal of hyperalgesia. When EOI lasted for 8 days or was removed on postoperative day 8, spontaneous activity and stimulus-evoked responses of ON-cell increased, contributing to the maintained hyperalgesia. In contrast, when the EOI lasted for 14 days, OFF-cell responses decreased, possibly participating in the maintenance of hyperalgesia with persistent EOI. Our results reveal that adaptive changes in the RVM were associated with orofacial pain following EOI placement and removal.SIGNIFICANCE STATEMENTA considerable proportion of patients suffered from chronic orofacial pain throughout life despite the therapies given or removal of potential etiological factors. However, current therapies lack effectiveness due to limited knowledge of the chronicity mechanisms. Using electrophysiological recording, combined with a behavioral test, we found that the prevailing descending facilitation in the rostral ventromedial medulla (RVM) participates in the maintenance of orofacial hyperalgesia following late removal of nociceptive stimuli, while the prevailing descending inhibition from the RVM may contribute to the reversal of orofacial hyperalgesia following early removal of nociceptive stimuli. Thus, variable clinical outcomes of orofacial pain may be associated with descending modulation and an optimal window of time may exist in the management of chronic orofacial pain.

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 nociceptive head withdrawal threshold (HWT) and activities of RVM ON- or OFF-cells were recorded before and after intra-RVM astrocyte gap junction blocker carbenoxolone (CBX) microinjection. RVM astrocytes were labelled immunohistochemically with glial fibrillary acidic protein (GFAP) and analysed semi-quantitatively. RESULTS: Persistent experimental dental occlusal interference-induced oro-facial hyperalgesia, as reflected in decreased HWTs, was partially inhibited by REOI at day 3 but not at day 8 after EOI placement. Increased GFAP-staining area occurred only in REOI 8 d group in which CBX could inhibit the maintained hyperalgesia; CBX was ineffective in inhibiting hyperalgesia in PEOI 14 d group. OFF-cell activities showed no change, but the spontaneous activity and responses of ON-cells were significantly enhanced that could be suppressed by CBX in REOI 8 d group. CONCLUSION: Rostral ventromedial medulla astrocytes may not participate in PEOI-induced oro-facial hyperalgesia or hyperalgesia inhibition by early REOI but are involved in the maintenance of oro-facial hyperalgesia by late REOI.

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. This article reviews these features of chronic orofacial pain, and outlines findings from studies in animal models of the behavioural characteristics and underlying mechanisms related to the development and maintenance of chronic orofacial pain and trigeminal neuropathic pain in particular. The review also considers the role of environmental and especially genetic factors in these models, focussing on findings of differences between animal strains in the features and underlying mechanisms of chronic pain. These findings are not only relevant to understanding underlying mechanisms and the variability between patients in the development, expression and maintenance of chronic orofacial pain, but also underscore the importance for considering the strain of the animal to model and explore chronic orofacial pain processes.

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. Tail or perioral heating evoked the TF and JMR, and the latency of the JMR was significantly shorter (P < 0.001) than that of the TF. Of 89 neurons recorded in RVM, 40 were classified as ON-cells, 27 as OFF-cells, and 22 as NEUTRAL-cells based on their responsiveness to heating of the tail. Heating at either site caused an increase in ON-cell and decrease in OFF-cell activity before the occurrence of the TF and JMR, but did not alter the activity of NEUTRAL cells. Likewise, noxious stimulation of the temporomandibular joint had similar effects on RVM neurons. These findings reveal that the JMR is a measure of the excitability of trigeminal and spinal nociceptive circuits in the CNS, and that the JMR as well as TF can be used for studying processes related to descending modulation of pain. The findings also support the view that RVM ON- and OFF-cells play an important role in the elaboration of diverse nociceptive behaviours evoked by noxious stimulation of widely separated regions of the body.

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. T1/T2 neurons showed an increase in firing at higher T1 temperatures, whereas T1 neurons did not. About half of the non-light/heat-sensitive T1/T2 neurons showed increased firing at higher T2 temperatures, whereas T2 neurons showed no such increase. The heat responses of heat-sensitive PMv neurons were significantly suppressed when monkeys shifted their attention from heat to light. The present findings suggest that heat-sensitive PMv neurons may be involved in motor responses to noxious heat, whereas light/heat-PMv neurons may be involved in emotional and motivational aspects of pain and inappropriate motor responses to allow escape from noxious 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 Rhodobacter sphaeroides, 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). Bilateral electromyographic (EMG) activities of the anterior digastric and masseter muscles were recorded continuously before and until 15 min after the MO application to the pulp. In 6 of these 23 rats and an additional 18 rats, the caudal medulla containing the ipsilateral and contralateral MDH was removed after euthanasia for subsequent Western Blot analysis of TLR4 expression in LPS-RS (n = 8) and vehicle (n = 8) groups and a naïve group (n = 8). The % change from baseline in the MO-evoked EMG activities within the anterior digastric muscles were significantly smaller in the LPS-RS group than the control group (two-way ANOVA, post hoc Bonferroni, P < 0.0001). Western Blot analysis revealed similar levels of TLR4 expression in the caudal medulla of the naïve, vehicle and LPS-RS groups. These novel findings suggest that TLR4 signaling in the caudal medulla may mediate MO-induced acute dental inflammatory pain in rats.

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 (0.2 µL, 20% MO) or vehicle (mineral oil) was topically applied to the dura or sinus, preceded by 10 µL of the ATP antagonist 2',3'-O-(2,4,6- trinitrophenyl) adenosine 5'-triphosphate (TNP-ATP, 0.1 mmol/L; n = 8) or 2-amino-5-phosphonopentanoic acid (APV, 0.05 mmol/L; n = 7) or phosphate-buffered saline (PBS as vehicle control; n = 10). RESULTS: Application of MO but not vehicle to the frontal dura significantly increased (P < .05) neck electromyographic activity whereas MO application to the superior sagittal sinus did not significantly increase neck electromyographic activity unless MO had previously been applied to the dura. Pre-treatment (i.t.) with TNP-ATP or APV but not vehicle control significantly reduced neck electromyographic activity evoked by MO application to the dura. CONCLUSIONS: These data suggest that noxious stimulation of the frontal dura (but not superior sagittal sinus) may enhance neck muscle activity that is P2X and NMDA receptor-dependent. These effects may contribute to neck muscle stiffness that occurs in some headache conditions.

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. These include its annual scientific meetings and the establishment of publications, guidelines, and other educational material as well as awards to support research and trainees. Many of these activities have included engagement with key partners who have also collaborated with the Society in national and international advocacy for pain. The review also outlines some of the features and factors underpinning the Society's national and international reputation and impact resulting from the many contributions that its members have made to the advances in pain research, education, and management over the past 40 years. The review concludes by noting that by way of its rich history and its past and present experiences, the Society is well positioned to continue its many activities and contributions to address the many challenges still facing the pain field in Canada and around the world.

Cet article passe en revue les principales caractéristiques et les principaux événements qui ont marqué les 40 ans d'histoire de la Société canadienne de la douleur, un chapitre de l'International Association pour l'étude de la douleur (IASP). On y décrit d'abord ses premières années de formation dans les années 1970 en tant que chapitres de l'Est et de l'Ouest de l'IASP, puis son évolution en tant que chapitre pancanadien et société. La formulation de son objectif, celui de favoriser la recherche sur la douleur, l'éducation à l'égard de celle-ci et sa prise en charge, ainsi que les nombreuses activités dans lesquelles la Société s'est engagée afin de renforcer cet objectif au cours des décennies suivantes, sont aussi mises en relief. Parmi celles-ci, on compte les réunions scientifiques annuelles et l'établissement de publications, de directives et d'autres matériels éducatifs, ainsi que de prix pour soutenir la recherche et les stagiaires. Bon nombre de ces activités comprenaient un engagement avec des partenaires qui ont également collaboré avec la Société dans le cadre de ses efforts de plaidoyer pour la douleur à l'échelle nationale et internationale. L'examen décrit également certaines des caractéristiques et des facteurs qui sous-tendent l'impact et la réputation internationale de la Société qui découlent des nombreuses contributions que ses membres ont apportées aux avancées en matière de recherche, à l'éducation sur la douleur et à la prise en charge de celle-ci au cours des 40 dernières années. La revue conclut en affirmant que par sa riche histoire et ses expériences passées et présentes, la Société est bien placée pour poursuivre ses nombreuses activités et continuer à apporter sa contribution afin de répondre aux nombreux défis auxquels le domaine de la douleur est encore confronté au Canada et dans le monde.

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. These muscles are involved in a number of functions including reflexes and the more complex sensorimotor functions of mastication, swallowing and speech. The review outlines the use by the brain of sensory inputs from oro-facial receptors in order to provide for exquisite sensorimotor control of the activity of the oro-facial muscles. It highlights the role in this sensorimotor control played by periodontal mechanoreceptors and their sensory inputs to the brain, and how oral implants in concert with the plastic capacity of the brain may, at least in part, compensate for reduced sensorimotor functioning when teeth are lost. It outlines findings of ageing-related decrements in oro-facial sensorimotor functions and control. The changes in oro-facial tissues and the brain that underlie these ageing-related functional alterations are also considered, along with adaptive and compensatory processes that utilise the brain's capacity for plasticity. The review also notes the evidence that rehabilitation that incorporates adjunctive approaches such as sensorimotor training paradigms in addition to oral prostheses such as implants may enhance these processes and help maintain or facilitate recovery of sensorimotor functioning in the elderly.

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). Naive rats (n = 3) had no treatment. Morphometric and immunohistochemical techniques quantified Anterior Digastric muscle myofibres' cross-sectional area (CSA) and myosin heavy chain (MyHC) isoform proportions. Significant ANOVAs were followed by post-hoc tests; p < 0.05 and 0.1 were considered to reflect levels of statistical significance. RESULTS: In naïve rats, the peripheral regions of the Anterior Digastric muscle was dominated by MyHC-IIx/b isoform and there were no MyHC-I isoforms; the central regions dominated by MyHC-IIx/b and MyHC-IIa isoforms. Compared with naive rats, tooth extraction produced, 8 (but not 4) weeks later, a decreased proportion of fast-contracting fatigue-resistant MyHC-IIa isoform (p = 0.08), and increased proportion of fast and intermediate fatigue-resistance MyHC-IIa/x/b isoform (p = 0.03). Dental implant placement following tooth extraction attenuated the extraction effects but produced a decreased proportion of fast-contracting fatiguable MyHC-llx/b isoform (p = 0.03) in the peripheral region, and increased inter-animal variability in myofibre-CSAs. CONCLUSIONS: Given the crucial role that the Anterior Digastric muscle plays in many vital oral functions (e.g., chewing, swallowing), these changes may contribute to the changes in oral sensorimotor functions that occur in humans following such treatments.

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. Nociceptive behavior was assessed by testing facial mechanical sensitivity pre-operatively and post-operatively (1-28 days). Intracortical microstimulation was also applied post-operatively in a series of microelectrode penetrations to map jaw and tongue motor representations in the face sensorimotor cortex by analyzing anterior digastric and genioglossus electromyographic activities evoked by microstimulation at histologically verified sites in face primary somatosensory cortex (face-SI) as well as face primary motor cortex (face-MI). Compared to sham, infraorbital nerve injury induced a significant (2-way repeated-measures analysis of variance, P < 0.001) bilateral decrease in facial mechanical threshold that lasted up to 28 days post-operatively. Nerve injury also induced a significant bilateral decrease compared to sham (P < 0.05) in the number of anterior digastric and/or genioglossus sites in face-MI and in face-SI. These findings indicate that trigeminal nerve injury induces neuroplastic alterations in jaw and tongue motor representations in face sensorimotor cortex that are associated with facial nociceptive behavior and that may contribute to sensorimotor changes following trigeminal nerve injury.