PubMed Health⌕ Search

Biomedical subjects

Barry J Sessle

Publications and source records attributed to Barry J Sessle.

At least 19 recordsLinked to original sources

ATP potentiates neurotransmission in the rat trigeminal subnucleus caudalis.

Ionotropic purine receptors (P2X) have been implicated in nociceptive neurotransmission. In this study, we examine the actions of the P2X receptor agonist alpha,beta methylene adenosine 5'-triphosphate on excitatory neurotransmission in neurons in the deep and superficial laminae of the trigeminal spinal subnucleus caudalis (Vc), which receives nociceptive inputs from the craniofacial region. Alpha, beta methylene adenosine 5'-triphosphate caused an increase in spontaneous excitatory neurotransmission (miniature excitatory postsynaptic currents) in neurons in deep but not superficial laminae of Vc; this effect could be inhibited by the P2X receptor antagonist 2,3-O-2,4,6-trinitrophenyl-ATP. Conversely, the TRPV1 agonist capsaicin caused an increase in miniature excitatory postsynaptic currents in neurons in the superficial but not deep laminae. These data suggest that alpha,beta methylene adenosine 5'-triphosphate acts on presynaptic terminals to increase glutamatergic neurotransmission in deep Vc neurons.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

Central sensitization induced in thalamic nociceptive neurons by tooth pulp stimulation is dependent on the functional integrity of trigeminal brainstem subnucleus caudalis but not subnucleus oralis.

We have previously demonstrated that application of the inflammatory irritant mustard oil (MO) to the rat molar tooth pulp induces central sensitization in nociceptive neurons within the contralateral ventroposterior medial (VPM) nucleus and posterior nuclear group (PO) of the thalamus as well as brainstem subnucleus caudalis (Vc) and subnucleus oralis (Vo). Since Vc and Vo are important relays of pulp afferent input to thalamus, the aim of this study was to test if local application of the synaptic blocker CoCl2 to Vc or Vo influences the pulp-induced thalamic central sensitization. The activity of 32 nociceptive-specific (NS) neurons within the rat VPM and immediately adjacent PO was recorded. Spontaneous activity, mechanoreceptive field (RF), mechanical activation threshold and evoked responses to graded mechanical stimuli were assessed before and after MO application to the pulp. MO application evoked immediate but short-lasting neuronal discharges in 21 of the 32 NS neurons tested, as well as central sensitization reflected in significant and long-lasting (> 60 min) RF expansion, decrease in activation threshold, and increase in graded pinch-evoked responses in all 32 NS neurons. CoCl2 applied to the ipsilateral Vc significantly attenuated these pulp-induced changes for 20 min or more. In contrast, CoCl2 applied to the ipsilateral Vo did not reverse this MO-induced central sensitization. Isotonic saline applied to Vc or Vo was also ineffective. These findings indicate that central sensitization induced in nociceptive neurons within VPM and PO by noxious stimulation of the tooth pulp is dependent upon the functional integrity of Vc but not Vo.

Animals↗

Quantitative analysis of surface EMG activity of cranial and leg muscles across sleep stages in human.

OBJECTIVE: The aim of this study was to make a quantitative analysis of the changes in cranial and limb muscle activity from wakefulness to light and deep sleep stages and during rapid eye movement (REM) sleep of normal subjects. METHODS: Polysomnographic recordings were made of the sleep of 9 healthy human subjects, including electromyograms of the suprahyoid, temporalis and masseter cranial muscles and the anterior tibialis limb muscle. Quantitative assessments of EMG activity were carried out with root mean square (RMS) and frequency-spectral analysis (FSA) methods. RESULTS: From wakefulness to sleep, a significant reduction (-25.2 to -71.2%; P < 0.01) was observed in EMG activity (for both RMS and FSA) of the 3 cranial muscles using both methods of analysis. The EMG activity of suprahyoid muscle further decreased from non-REM to REM sleep (-17.8 to -43.0%; P < 0.01). In contrast, the EMG activity of the anterior tibialis muscle was only slightly reduced across sleep stages and did not further reduce during REM sleep. During REM sleep, all the 4 muscles maintained minimal activity. CONCLUSIONS: The maintenance of muscle activity during REM sleep suggests that a minimal level of activity is required to preserve physiological functions (e.g. airway patency, posture) related to homeostasis and bodily protection. SIGNIFICANCE: This study suggests that quantitative sleep EMG analysis is important for understanding the mechanisms of sleep-related movement disorders or when objective assessment of changes in EMG activity are needed for diagnostic purposes or for the assessment of drug efficiency.

Adult↗

Ketamine attenuates glutamate-induced mechanical sensitization of the masseter muscle in human males.

The purpose of the present study was to determine whether glutamate-induced mechanical sensitization of the masseter muscle in human volunteers involves activation of peripheral N-methyl-D-aspartate (NMDA) receptors. Healthy male volunteers (n=18) participated in this randomized, two-session study. During each session, the volunteers received two injections into the right masseter muscle. An initial injection of glutamate (1 M, 0.2 ml) alone was followed 30 min later by a second injection of glutamate alone or glutamate combined with ketamine (10 mM). Pressure pain threshold (PPT) was assessed over the right masseter muscle at and 2 cm above the injection site, as well as over the right temporalis muscle and left masseter muscle prior to the first injection. The PPT was reassessed at all four sites every 5 min from 10 to 30 min after the second injection and once again 60 min after the second injection. Glutamate-evoked muscle pain, pain area and the sensory pain response index of the McGill pain questionnaire were all significantly reduced by co-injection of ketamine. The mean PPT values were significantly decreased by approximately 10%, 10, 15 and 25 min after injection of glutamate, but only over the site of injection. Co-injection of ketamine with glutamate also completely blocked the glutamate-induced mechanical sensitization 15 min post-injection as compared with glutamate alone. The lack of spread of mechanical sensitization outside the area of glutamate injection is consistent with the view that glutamate-induced mechanical sensitization results from a peripheral mechanism. The attenuation of glutamate-induced mechanical sensitization by ketamine suggests that this effect is mediated, in part, through activation of peripheral NMDA receptors.

Adult↗

Unilateral application of an inflammatory irritant to the rat temporomandibular joint region produces bilateral modulation of the jaw-opening reflex.

The aim of this study was to determine the effect of unilateral acute inflammation of craniofacial deep tissues on the ipsilateral and contralateral jaw-opening reflex (JOR). The effects of mustard oil (MO), injected into the temporomandibular joint region, were tested on the JOR recorded in the digastric muscle and evoked by low-intensity electrical stimulation of the ipsilateral and contralateral inferior alveolar nerve in anesthetized rats. The MO injection induced a long-lasting suppression of the amplitude of both ipsilaterally and contralaterally evoked JOR, although the latency and duration of the JOR were unaffected. The suppressive effect was more prominent for the contralaterally evoked JOR, and observed even when background activity in the digastric muscle was increased by the MO injection. The results indicate that changes in the JOR amplitude following MO injection do not simply reflect alterations in motoneuronal excitability, and suggest that inflammation of deep craniofacial tissues modulates low-threshold sensory transmission to the motoneurons.

Analysis of Variance↗

Peripheral NMDA receptor modulation of jaw muscle electromyographic activity induced by capsaicin injection into the temporomandibular joint of rats.

We have previously documented that peripheral N-methyl-d-aspartate (NMDA) receptor mechanisms are involved in nociceptive reflex increases in jaw muscle activity to injection of mustard oil or glutamate into the rat temporomandibular joint (TMJ). The aim of the present study was to determine whether peripheral NMDA receptor mechanisms are also involved in the nociceptive reflex responses in the jaw muscles evoked by injection of the inflammatory irritant and algesic chemical capsaicin into the TMJ. The effects of peripheral injection of NMDA receptor antagonists, MK-801 and APV, on the increases in electromyographic (EMG) activities of digastric and masseter muscles reflexly evoked by capsaicin injection into the TMJ were tested in halothane-anesthetized male rats. The capsaicin injection following pre-injection of vehicle evoked significant increases in EMG activity in both digastric and masseter muscles whereas pre-injection of MK-801 or APV into the TMJ resulted in a significant concentration-related reduction in the magnitude of capsaicin-evoked digastric and masseter EMG activity (ANOVA-on-ranks, P < 0.05). This finding indicates that capsaicin-evoked digastric and masseter EMG activity can be attenuated by pre-injection into the TMJ of NMDA receptor antagonists, and that the activation of peripheral NMDA receptors may be important in the mechanisms whereby capsaicin evokes nociceptive trigeminal responses.

Analysis of Variance↗

Neck muscle length modulates nociceptive reflex evoked by noxious irritant application to rat neck tissues.

The application of mustard oil (MO), a small-fibre excitant and inflammatory irritant, into neck paraspinal muscles of the rat has been shown to produce a significant reflexive increase in electromyographic (EMG) activity in both neck and jaw muscles. It is possible that this nociceptive reflex activity is influenced by muscle length since recent evidence indicates that abnormal neck posture may be associated with cervical musculoskeletal disorders and pain. Therefore, the aim of this study was to test if muscle length modulates this nociceptive reflex response. Three different experimental procedures were employed in rats under halothane anesthesia: (1) MO injected into the left deep neck muscles with the rat placed in a straight body position (Straight group, n = 7); (2) MO injected into lengthened left deep neck muscles with the rat's neck rotated 45 degrees to the right with respect to the head (Stretched group, n = 11); and (3) MO injected into the right deep neck muscles with the rat's neck rotated 45 degrees to the right (Relaxed group, n = 9). The EMG activity of the deep neck, trapezius, and digastric muscles was bilaterally recorded, rectified and integrated into area under the curve (AUC). Control injections of the vehicle, mineral oil, did not evoke any muscle activity but MO evoked EMG activity in the ipsilateral deep neck and trapezius muscles of the Stretched group that was significantly greater than that evoked in the same muscles in the Straight and Relaxed groups. Also, the MO-evoked EMG activity in the contralateral deep neck muscles of the Stretched and Relaxed groups was greater than that of the corresponding muscles in the Straight group. The MO-evoked activity in the digastric, a jaw muscle whose length was not changed, did not show any significant difference between the three groups. These findings indicate that MO application to the rat deep neck muscles results in a larger nociceptive reflex in deep neck and trapezius muscles when they are stretched. This enhanced muscle activity could be associated with changes in the susceptibility of the neck muscles to pain or damage.

Anesthesia↗

Neural mechanisms of temporomandibular joint and masticatory muscle pain: a possible role for peripheral glutamate receptor mechanisms.

The purpose of the present review is to correlate recent knowledge of the role of peripheral ionotropic glutamate receptors in the temporomandibular joint and muscle pain from animal and human experimental pain models with findings in patients. Chronic pain is common, and many people suffer from chronic pain conditions involving deep craniofacial tissues such as temporomandibular disorders or fibromyalgia. Animal and human studies have indicated that the activation of peripheral ionotropic glutamate receptors in deep craniofacial tissues may contribute to muscle and temporomandibular joint pain and that sex differences in the activation of glutamate receptors may be involved in the female predominance in temporomandibular disorders and fibromyalgia. A peripheral mechanism involving autocrine and/or paracrine regulation of nociceptive neuronal excitability via injury or inflammation-induced release of glutamate into peripheral tissues that may contribute to the development of craniofacial pain is proposed.

Animals↗

Pain effects of glutamate injections into human jaw or neck muscles.

AIMS: To document and compare the intensity, localization, and quality of pain evoked by glutamate injections into the human masseter or splenius muscles and to determine the effect of glutamate-evoked pain on the pressure pain thresholds (PPTs) in both jaw and neck muscles. METHODS: Twenty-six healthy men were given painful injections of glutamate (1.0 mol/L) and control injections of isotonic saline (0.165 mol/L) into the masseter and splenius muscles. The subjects rated the perceived intensity of pain on a visual analog scale (VAS), drew the area of the pain on maps of the face and neck, and filled out a Danish version of the McGill Pain Questionnaire (MPQ). PPTs were used to assess the sensitivity of the masseter and splenius muscles to mechanical stimuli (n = 11). RESULTS: Glutamate injection into the masseter or splenius evoked pain lasting almost 10 minutes. Peak pain intensity usually occurred within 2 minutes of the injection, and VAS scores of peak pain were significantly higher for the masseter muscle compared with the splenius muscle (paired t test, P = .003). The pain area from the masseter injections did not extend into the neck region, although in some subjects the pain from the neck region extended into the temporal region. There were no significant relationships between the area of perceived pain and the VAS pain scores (Pearson correlation, P > .297). Glutamate-evoked pain in either the masseter or splenius muscles was associated with significant decreases in masseter or splenius PPTs, respectively (2-wayANOVAs, P < .016). Isometric saline injections were almost pain-free and caused no PPT changes. CONCLUSION: The data suggest that the masseter muscle is more sensitive to glutamate injections and mechanical stimuli than the splenius muscle. The relatively limited overlap between the sensory manifestations of pain from masseter and splenius muscles may have potential implications for diagnosis and management of myofascial pain complaints in the craniofacial and neck region.

Adult↗

Simultaneous modulation of the exteroceptive suppression periods in the trapezius and temporalis muscles by experimental muscle pain.

OBJECTIVE: To investigate whether the exteroceptive suppression (ES) periods in the trapezius and temporalis muscles could be simultaneously modulated by either experimental trapezius muscle pain or temporalis muscle pain. METHODS: Fourteen healthy volunteers participated in two sessions with randomised injections of either hypertonic or isotonic saline into the right trapezius muscle or right temporalis muscle. The pain intensity was continuously scored on a 10 cm electronic visual analogue scale. During muscle contraction, the early (ES1) and late (ES2) reflex in the temporalis and late (ES2) reflex in the trapezius elicited by electrical stimulation of the right infraorbital nerve were recorded pre-, during-, and post-injection. RESULTS: Hypertonic saline injection induced local muscle pain and referred pain with the maximal pain intensity of 6.3+/-0.5 cm in the right trapezius and 6.7+/-0.6 cm in the right temporalis muscles. Injection of either hypertonic or isotonic saline into the right trapezius muscle was associated with significantly shortened ES2 duration and offset time in the injected right trapezius muscle. Only injection of hypertonic saline into the right trapezius muscle could significantly reduce the ES2 offset time and decrease the degree of suppression of ES2 in the right temporalis and left trapezius muscles. Injection of either hypertonic or isotonic saline into the right trapezius muscle evoked no changes in ES2 parameters in the left temporalis muscle. Injection of hypertonic saline, but not isotonic saline, into the right temporalis muscle caused a significantly shorter ES2 offset time and shorter ES2 duration bilaterally in the temporalis and trapezius muscles. CONCLUSIONS: The findings of the present study provide evidence for a bi-directional effects reflecting convergence of muscle afferents from the trigeminal and upper cervical neural systems in humans, which may partly underlie the manifestations of pain referral between these two areas.

Adult↗

Associations between pain and neuromuscular activity in the human jaw and neck muscles.

The aim of this study was to test the effects of glutamate-evoked jaw or neck muscle pain on electromyographic (EMG) activity of jaw and neck muscles in humans. EMG recordings were made from left (MAL) and right (MAR) masseter muscles, and right sternocleidomastoid (SCM) and splenius (SP) muscles in three different head positions (head rest, head back, head right) or during maximal jaw clenching in 19 men. Glutamate (1 M) or isotonic saline was injected into MAR or SP, and induced pain was recorded on visual analogue scales. EMG activity in MAL and MAR was increased in the head back position compared to head rest and head right positions, whereas EMG activity in SCM and SP was progressively increased as the head was moved from rest position to head back to head right positions. Glutamate-evoked MAR pain was associated with increases in EMG activity in MAR, SCM and SP at rest but not in the head back or head right positions. Glutamate-evoked SP pain was associated with an increase in SP EMG activity at rest and a decrease in SCM EMG activity in the head right position. Decreases in jaw clench-related EMG activity were observed in MAL, MAR and SCM muscles only during glutamate-evoked MAR pain. Isotonic saline injections induced no pain or EMG changes. In conclusion, experimental neck pain is not associated with tonic increases in jaw EMG activity although jaw muscle pain can be linked to increases in neck EMG activity with the head and jaw at rest.

Adult↗

Plasticity in corticomotor control of the human tongue musculature induced by tongue-task training.

Transcranial magnetic stimulation (TMS) has been used to assess characteristics of the corticomotor control of the jaw muscles, but less is known about the cortical control of the human tongue and its modification by training. The aim of the present study was to determine the effect of training humans in a novel tongue-protrusion task for 1 week on corticomotor excitability as assessed by changes in electromyographic activity elicited in the tongue musculature by TMS, and in the tongue cortical motor map revealed by TMS. Eleven healthy subjects participated. Stimulus-response curves were generated from the motor evoked potentials (MEPs) recorded in the tongue musculature and, from the first dorsal interosseos (FDI) muscle as a control, at three time periods: at baseline, immediately after the 1-week training period, and at 2-weeks follow-up. In addition, the corticomotor representations of the tongue and FDI muscles were mapped on a 1 x 1 cm scalp grid. The tongue-training task required each subject to protrude the tongue onto a force transducer placed in front of the subject, and consisted of a relax-protrude-hold-relax cycle lasting 12.5 s with 1 N as the target at the hold phase. The subjects repeated this task for 60 min every day for 1 week. All subjects reported moderate levels of fatigue in the tongue during the first training day; however, these subjective reports decreased during the week (ANOVA P<0.001), and the subjects showed a progressive increase in their ability to perform the task successfully ( P<0.001). The threshold for evoking MEPs by TMS in the tongue musculature was significantly decreased after the last training day compared with baseline and the 2-weeks follow-up ( P<0.001). The amplitude of the MEPs in the tongue musculature was significantly increased at higher intensities of TMS after the last training day but returned to baseline values at the 2-weeks follow-up (P = 0.005). No significant effect of the training on MEPs in the FDI was observed (P = 0.493). Analysis of the corticomotor topographic maps revealed a significant ( P<0.05) increase in excitability and, hence, the cortical area from which TMS could evoke MEPs in the tongue, although the center of gravity representation for the tongue or FDI muscles remained stable. The present findings suggest that a specific and reversible plasticity of the corticomotor excitability related to tongue muscle control can be induced when humans learn to perform successfully a novel tongue task.

Adult↗

Activation of peripheral NMDA receptors contributes to human pain and rat afferent discharges evoked by injection of glutamate into the masseter muscle.

Peripheral N-methyl-d-aspartate (NMDA) receptors are found in deep tissues and may play a role in deep tissue pain. Injection of the endogenous NMDA receptor agonist glutamate into the masseter muscle excites deep craniofacial afferent fibers in rats and evokes pain in human subjects. It is not clear whether peripheral NMDA receptors play a role in these effects of glutamate. Accordingly, the effect of NMDA on afferent activity as well as the effect of locally administered NMDA receptor antagonists on glutamate-evoked afferent discharges in acutely anesthetized rats and muscle pain in human subjects was examined. Injection of NMDA into the masseter muscle evoked afferent discharges in a concentration-related manner. It was found that the NMDA receptor antagonists 2-amino-5-phosphonvalerate (APV, 10 mM), ketamine (10 mM), and dextromethorphan (40 mM) significantly decreased glutamate-evoked afferent discharges. The effects of APV and ketamine, but not dextromethorphan, were selective for glutamate-evoked afferent discharges and did not affect hypertonic saline-evoked afferent discharges. In human experiments, it was found that 10 mM ketamine decreased glutamate-evoked muscle pain but had no effect on hypertonic saline-evoked muscle pain. These results indicate that injection of glutamate into the masseter muscle evokes afferent discharges in rats and muscle pain in humans in part through activation of peripheral NMDA receptors. It is conceivable that activation of peripheral NMDA receptors may contribute to masticatory muscle pain and that peripherally acting NMDA receptor antagonists could prove to be effective analgesics for this type of pain.

Adult↗

Glutamate-evoked pain and mechanical allodynia in the human masseter muscle.

The present study examined the effect of peripheral administration of the excitatory amino acid (EAA) glutamate on the intensity of perceived pain and pressure pain thresholds (PPTs) in healthy young women (n=17) and men (n=18). Two injections separated by 25 min of 0.2 ml, 1.0M glutamate into the masseter muscle produced significantly higher scores of pain on 0-10 cm visual analogue scales (VAS) in women than in men (analysis of variance, ANOVA: P<0.001). There was no significant difference between the VAS scores for the first and the second injections in either men or women. The PPTs determined in the masseter muscle were significantly reduced following the first injection and further significantly reduced after the second injection (ANOVA: P<0.001). Furthermore, the PPTs were reduced to a similar extent in both women and men (maximum 44-56%), suggesting that gender did not influence the process of sensitization. There were no significant difference in VAS scores or PPTs between women taking oral contraceptives (n=9) and those who did not (n=8) (ANOVAs: P=0.709, P=0.153). It is concluded that the VAS scores produced by intramuscular administration of 1.0M glutamate may reflect a gender-dependent activation of nociceptive pathways which, in part, may be mediated through peripheral EAA receptors. The reduction of PPTs in the masseter muscle following administration of glutamate in a concentration of 1.0M may reflect allodynia to mechanical stimuli. This process of sensitization was not gender-dependent. The present results suggest that injection of 1.0M glutamate into the masseter muscle may provide a useful experimental method to test sensitization and efficacy of peripheral EAA receptor antagonists in human subjects.

Adult↗