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.

Pterygoid muscle activity in speech: A preliminary investigation.

BACKGROUND: Speaking depends on refined control of jaw opening and closing movements. The medial pterygoid muscle (MPT), involved in jaw closing, and the lateral pterygoid muscle (LPT), involved in jaw opening, are two key mandibular muscles in mastication and are likely to be recruited for controlled movements in speech. OBJECTIVES: Three hypotheses were investigated, that during speech the MPT and LPT: (1) were both active, (2) but exhibited different patterns of activity, (3) which fluctuated with the vowels and consonants in speech. METHODS: Intramuscular EMG recordings were made from the right inferior head of the LPT and/or the right MPT in five participants during production of 40 target nonsense words (NWs) consisting of three syllables in the form /V1 C1 V2 C2 ə/ (V = vowel; C = consonant; ə = unstressed, reduced vowel), spoken by each participant 10 times per NW; analysis focussed on the target syllable, C1 V2 . RESULTS: Both MPT and LPT exhibited robust increases in EMG activity during utterance of most NWs, relative to rest. Peak LPT activation was time-locked to the final part of the target consonant (C1 ) interval when the jaw begins opening for the target vowel (V2 ), whereas peak MPT activation occurred around the temporal midpoint of V2 , when the jaw begins closing for C2 . EMG amplitude peaks differed in magnitude between "high" vowels, i.e., for which the tongue/jaw are high (e.g., in SEEK), and "low" vowels, i.e., for which the tongue/jaw are low (e.g., in SOCK). CONCLUSIONS: These novel findings suggest a key role for the LPT and MPT in the fine control of speech production. They imply that speech may impose major synergistic demands on the activities of the MPT and the LPT, and thereby provide insights into the possible interactions between speech activities and orofacial activities (e.g. mastication) and conditions (e.g. Temporomandibular Disorders) that involve the masticatory muscles.

Threshold variations of medial pterygoid single motor units during vertical or horizontal force tasks.

OBJECTIVES: To test the hypotheses that (a) the force thresholds at onset of medial pterygoid muscle single motor unit (SMU) activity do not decrease with an increase in the rate of force generation in standardised vertical or horizontal jaw-force tasks, and (b) there is evidence for functional heterogeneity within the medial pterygoid muscle. METHODS: In 14 healthy participants, electromyographic recordings of the right medial pterygoid muscle were performed with intramuscular fine-wire electrodes during four isometric force tasks: vertical, horizontal contralateral, horizontal protrusion and horizontal ipsilateral, performed at two rates of force development (slow ramp, fast ramp). Computer tomography scans confirmed electrode location within the muscle, which was divided into medial and lateral parts. Force thresholds of onset of discriminated SMUs were compared between rates in each task; significance accepted at p < 0.05. RESULTS: Of 45 SMU force thresholds studied in one or more tasks, there was no significant difference between slow and fast ramp within each force task, except slow ramp thresholds from the lateral part during the vertical force task were significantly higher than fast ramp thresholds. Reversals of recruitment order between tasks provided evidence for functional heterogeneity within the muscle. Force thresholds of the vertical tasks (range: 1-292.6 N) were mostly higher than for the horizontal tasks (range: 0.1-12.5 N). CONCLUSION: The data are consistent with the proposal that the medial pterygoid muscle stabilises the jaw in the vertical plane during isometric force generation in the jaw closing, as well as horizontal directions.

Functional properties of single motor units in the human medial pterygoid muscle: Thresholds.

BACKGROUND: Little is known regarding the functional properties of single motor units (SMUs) in the medial pterygoid muscle (MPt) during jaw movements. OBJECTIVES: The aims are (a) to report the thresholds of onset of MPt SMUs during 4 goal-directed jaw movement tasks, and (b) to determine whether the threshold of onset of SMU activation varies with the velocity of jaw movement and the location within the muscle. METHODS: Intra-muscular electrodes were inserted in the right MPt of 18 participants performing ipsilateral (right), contralateral, protrusive and opening-closing jaw movements recorded at 2 velocities. Task phases were as follows: BEFORE, OUT, HOLDING, RETURN and AFTER. SMU onset thresholds were determined from the displacement (mm) of the lower mid-incisor point. Electrode location within 4 arbitrary muscle divisions was determined with computer tomography. Statistical tests: Spearman's correlations, Kruskal-Wallis tests; significance accepted at P < .05. RESULTS: A significant inverse relation occurred between velocity and threshold for the RETURN of the ipsilateral movement (n = 62 SMU thresholds), while a significant positive relation occurred for the OUT of the contralateral movement (n = 208); there were no significant associations for the protrusive (n = 131) and opening-closing (n = 58) tasks. Significant threshold differences occurred across the 4 muscle divisions only during the OUT of the contralateral and protrusive movements. Some evidence was provided for gender differences in MPt SMU properties. CONCLUSIONS: The absence of a significant inverse relation between velocity and SMU threshold for most recorded movements suggests the MPt acts as a stabilizer of the jaw in horizontal and opening-closing jaw movements.

Altered Brainstem Pain Modulating Circuitry Functional Connectivity in Chronic Painful Temporomandibular Disorder.

There is evidence from preclinical models of chronic pain and human psychophysical investigations to suggest that alterations in endogenous brainstem pain-modulation circuit functioning are critical for the initiation and/or maintenance of pain. Whilst preclinical models have begun to explore the functioning of this circuitry in chronic pain, little is known about such functioning in humans with chronic pain. The aim of this investigation was to determine whether individuals with chronic non-neuropathic pain, painful temporomandibular disorders (TMD), display alterations in brainstem pain-modulating circuits. Using resting-state functional magnetic resonance imaging, we performed static and dynamic functional connectivity (FC) analyses to assess ongoing circuit function in 16 TMD and 45 control subjects. We calculated static FC as the correlation of functional magnetic resonance imaging signals between regions over the entire scan and dynamic FC as the correlation of signals in short (50s) windows. Compared with controls, TMD subjects showed significantly greater (static) FC between the rostral ventromedial medulla and both the subnucleus reticularis dorsalis and the region that receives orofacial nociceptive afferents, the spinal trigeminal nucleus. No differences were found in other brainstem pain-modulating regions such as the midbrain periaqueductal gray matter and locus coeruleus. We also identified that TMD subjects experience greater variability in the dynamic functional connections between the rostral ventromedial medulla and both the subnucleus reticularis dorsalis and spinal trigeminal nucleus. These changes may underlie enhanced descending pain-facilitating actions over the region that receives nociceptive afferents, ultimately leading to enhanced nociceptive transmission to higher brain regions and thus contributing to the ongoing perception of pain. PERSPECTIVE: Psychophysical studies suggest that brainstem pain-modulation circuits contribute to the maintenance of chronic pain. We report that individuals with painful TMD display altered static and dynamic FC within the brainstem pain-modulation network. Modifying this circuitry may alter an individual's ongoing pain.

Effect of Expectation on Pain Processing: A Psychophysics and Functional MRI Analysis.

Pain is a complex phenomenon that is highly modifiable by expectation. Whilst the intensity of incoming noxious information plays a key role in the intensity of perceived pain, this intensity can be profoundly shaped by an individual's expectations. Modern brain imaging investigations have begun to detail the brain regions responsible for placebo and nocebo related changes in pain, but less is known about the neural basis of stimulus-expectancy changes in pain processing. In this functional magnetic resonance imaging study, we administered two separate protocols of the same noxious thermal stimuli to 24 healthy subjects. However, different expectations were elicited by different explanations to subjects prior to each protocol. During one protocol, pain intensities were matched to expectation and in the other protocol they were not. Pain intensity was measured continuously via a manually operated computerized visual analogue scale. When individuals expected the stimulus intensity to remain constant, but in reality it was surreptitiously increased or decreased, pain intensity ratings were significantly lower than when expectation and pain intensities were matched. When the stimulus intensities did not match expectations, various areas in the brain such as the amygdala, anterior cingulate cortex (ACC), dorsolateral prefrontal cortex (dlPFC), and the midbrain periaqueductal gray matter (PAG) displayed significantly different patterns of activity compared to instances when stimulus intensity and pain expectations were matched. These results show that stimulus-expectancy manipulation of pain intensity alters activity in both higher brain and brainstem centers which are known to modulate pain under various conditions.

Reorganization of Masseter and Temporalis Muscle Single Motor Unit Activity During Experimental Masseter Muscle Pain.

AIMS: To test the hypothesis that experimental noxious stimulation of the right masseter muscle results in a reorganization of motor unit activity within the right temporalis and right masseter muscles during jaw closing tasks. METHODS: A total of 20 healthy participants received hypertonic saline (5% sodium chloride) infusion into the right masseter muscle, and pain intensity was maintained at 40-60/100 mm on a visual analog scale. Standardized isometric biting tasks were performed with an intraoral force transducer while single motor units (SMUs) were recorded from the right masseter and temporalis muscles. Tasks were repeated in four blocks: block 1 (baseline 1), block 2 (hypertonic saline [HS] infusion or isotonic saline [IS] infusion), block 3 (infusion of the other solution), and block 4 (baseline 2). The occurrences of SMUs were tabulated across blocks. Statistical significance was considered to be P < .05. RESULTS: There were no significant effects of block on the tasks. A total of 83 SMUs were discriminated in the temporalis and 58 in the masseter. For the comparison between HS and IS across tasks, the occurrences of 74.6% to 82.8% of SMUs were unchanged (70.2% to 94.3% for masseter), while during HS, 10.3% to 17.1% of SMUs were recruited (0% to 12.8%, masseter) and 6.9% to 12.7% were de-recruited (5.7% to 17%, masseter). CONCLUSION: The present findings suggest that most biting-task-related jaw muscle SMUs remain active during experimental muscle noxious stimulation. There was some evidence in both the anterior temporalis and masseter muscles for motor unit recruitment and de-recruitment consistent with a motor unit reorganization during experimental pain.

Simultaneous Noxious Stimulation of the Human Anterior Temporalis and Masseter Muscles. Part II: Effects on Jaw Muscle Electromyographic Activity.

AIMS: To test the hypotheses that, in comparison to control, the effects of simultaneous noxious stimulation of the right masseter and anterior temporalis muscles on jaw muscle activity (1) vary with the task; (2) are different between different agonist or antagonist muscles involved in a task; and (3) are correlated with mood or pain-related cognition scores. METHODS: In 15 asymptomatic participants, recordings were made of jaw movement and electromyographic (EMG) activity of the right digastric and bilateral masseter and anterior temporalis muscles during standardized open/close and free and standardized chewing tasks. The tasks were repeated in three blocks: block 1 (baseline), block 2 (during simultaneous infusion of 5% hypertonic or 0.9% isotonic saline infusion into the right masseter and anterior temporalis muscles), and block 3 (infusion sequence reversed). The Depression, Anxiety and Stress Scales questionnaire was completed prior to the experiment, and the Pain Catastrophizing Scale was completed before and after the experiment. Linear mixed-effects model analysis compared root mean square (RMS) EMG activity under baseline, hypertonic saline, and isotonic saline (control), and Spearman correlations between RMS and psychologic scores were calculated. P < .05 was considered significant. RESULTS: The significant effects of pain on the activity of a jaw muscle varied with the task, were different between different agonist and antagonist muscles in a task, and were significantly correlated with some of the psychologic scores. Qualitatively, the effects noted in a particular muscle could be different between different participants. CONCLUSION: Simultaneous noxious masseter and anterior temporalis stimulation results in changes in jaw muscle activity that can vary with the task, the muscle, the participant, and some psychologic variables.

Simultaneous Noxious Stimulation of the Human Anterior Temporalis and Masseter Muscles. Part I: Effects on Jaw Movements.

AIMS: To test the hypotheses that, in comparison to control (isotonic saline), simultaneous noxious stimulation (hypertonic saline) of the masseter and anterior temporalis muscles would result in (1) reductions in amplitude and velocity of jaw movements during standardized open/close jaw movements and during free and standardized chewing and (2) changes in amplitude and velocity of jaw movements that relate to higher levels of negative mood or pain-related thoughts. METHODS: Standardized open/close and free and standardized chewing were recorded in 15 asymptomatic participants in three blocks: block 1 (baseline), block 2 (during 5% hypertonic or 0.9% isotonic saline infusion into the right masseter and anterior temporalis muscles simultaneously), and block 3 (infusion sequence reversed). The Depression, Anxiety, and Stress Scale (DASS-21) and the Pain Catastrophizing Scale (PCS) were completed by the participants before the experiment, and the PCS was completed after the experiment. The amplitude and velocity of opening and closing movements for each task were compared between blocks (repeated-measures analysis of variance). Spearman rank correlation coefficient was used to explore correlations. Statistical significance was considered to be P < .05. RESULTS: In comparison to isotonic saline control, hypertonic saline resulted in significantly smaller opening and closing amplitudes and lower velocity during closing in free chewing, but no significant effects in the open/close task or standardized chewing. There were significant correlations between PCS scores and amplitude or velocity during isotonic saline and baseline, but not hypertonic saline. CONCLUSION: The pain-related reduction in amplitude and/or velocity of free chewing is consistent with the Pain Adaptation Model, but the absence of effects on the open/close task and standardized chewing is not. The few significant correlations between psychologic variables and jaw movement may reflect the low scores.

Single motor units from the medial pterygoid muscle can be active during isometric horizontal and vertical forces.

OBJECTIVES: To determine (a) whether the medial pterygoid muscle is active in an isometric vertical force task and in isometric horizontal force tasks in the contralateral, protrusion and ipsilateral directions; (b) whether the same single motor units (SMUs) could be active across different directions of isometric force generation; and (c) whether different regions of the medial pterygoid muscle exhibit different patterns of SMU activation during the generation of any one direction of isometric force. METHODS: Intramuscular electromyographic (EMG) recordings were made from the right medial pterygoid muscle in 15 healthy participants during isometric force tasks: vertical and horizontal contralateral, protrusion and ipsilateral. A computed tomography scan divided the EMG recording site into a medial or lateral part in each participant. Single motor units were discriminated in each task. RESULTS: Medial pterygoid SMU activity was recorded in 100% of participants for the vertical biting tasks, 86% of participants for the horizontal contralateral and horizontal protrusion tasks and 57% of the horizontal ipsilateral tasks. Of the 72 SMUs that were discriminated, 36% were active in all tasks; 18% were active only in the vertical tasks and 17% were active in the vertical, horizontal contralateral and horizontal protrusion tasks. The proportion of SMUs that was active in at least 1 horizontal task in the lateral part (33/39) was significantly higher than the proportion (21/33) in the medial part (Chi-Square, P < 0.05). CONCLUSION: The data are consistent with a stabilisation role for the medial pterygoid muscle in isometric jaw forces in the vertical and horizontal planes.

Experimental noxious stimulation of the right masseter muscle does not affect bilateral masseter and temporalis muscle activity and force parameters during standardised isometric biting tasks.

AIM: To determine if the electromyographic (EMG) activity of the left and right masseter and anterior temporalis muscles is altered by experimental right masseter muscle noxious stimulation during goal-directed isometric biting tasks in asymptomatic humans. METHODS: Isometric biting tasks (slow and fast ramp biting tasks, 2-step biting task) were performed on an intraoral force transducer in 18 participants during the following blocks: baseline block, hypertonic saline infusion into the right masseter muscle (painful block) and isotonic saline infusion into the right masseter (control block). Bipolar surface electrodes recorded EMG activity from the bilateral masseter and anterior temporalis muscles. A 100-mm visual analogue scale (VAS) quantified pain intensity, and the McGill Pain Questionnaire (MPQ), the Depression, Anxiety and Stress Scales-21 (DASS-21) and the Pain Catastrophizing Scale (PCS) were completed. Repeated measures ANOVA assessed the effects of pain on the force rates (N/s), force amplitudes (N) and the root mean square (RMS) jaw muscle EMG activity across blocks. Statistical significance accepted at P < 0.05. RESULTS: VAS scores were significantly (P < 0.001) higher during hypertonic than isotonic saline infusion blocks. There was no significant effect of pain on the force rates, or force levels or the RMS EMG activity of each masseter and anterior temporalis muscle. CONCLUSION: The findings suggest that experimentally induced right masseter muscle pain does not modify force or surface jaw muscle EMG activity during isometric biting tasks.

Reorganization of motor unit activity at different sites within the human masseter muscle during experimental masseter pain.

The aims were to test the hypotheses that experimental masseter muscle pain leads to recruitment and/or derecruitment of motor units at different sites within the masseter and that the patterns of change in motor unit activity differ between sites. Single motor unit (SMU) activity was recorded at two sites within the right masseter [superior/anterior, inferior/posterior (IP)] during isometric biting tasks (ramp, step level) on an intraoral force transducer in 17 participants during three experimental blocks comprising no infusion (baseline), 5% hypertonic saline infusion (pain), or isotonic saline infusion (control). A visual analog scale (VAS) was used to score pain intensity. The VAS scores were statistically significantly greater during infusion of hypertonic saline than during infusion of isotonic saline. No significant differences in force levels and rates of force change were found between experimental blocks. In comparison with isotonic saline infusion, SMUs could be recruited and derecruited at both sites during hypertonic saline infusion. The frequency of recruitment or derecruitment, in comparison with no change, was statistically significantly greater at the IP site than at the superior/anterior site. Experimental noxious masseter stimulation results in a reorganization of motor unit activity throughout the muscle, and the pattern of reorganization may be different in different regions of the muscle.

The Effects of Experimental Temporalis Muscle Pain on Jaw Muscle Electromyographic Activity During Jaw Movements and Relationships with Some Psychological Variables.

AIMS: To determine if the effects of experimental temporalis muscle pain on jaw muscle activity vary with the jaw task performed, jaw displacement magnitude, participant being studied, and with psychological measures. METHODS: Jaw movement was tracked, and electromyographic (EMG) activity was recorded from the masseter and anterior temporalis and digastric muscles in 14 asymptomatic participants during standardized opening/closing jaw movement, free chewing, and standardized chewing tasks. Tasks were repeated in three blocks: Block 1 (baseline), Block 2 (during 5% hypertonic or 0.9% isotonic saline infusion into the anterior temporalis), and Block 3 (during infusion of the opposite solution). Participants also completed the Depression, Anxiety, and Stress Scales 21 (DASS 21), the Fear of Pain Questionnaire (FPQ III), the Pain Self-Efficacy Questionnaire (PSEQ), and the Pain Catastrophizing Scale (PCS). Analyses involved linear mixed-model analysis and Pearson correlations. P < .05 was considered statistically significant. RESULTS: The presence of a significant difference in jaw muscle EMG activity between hypertonic and isotonic saline infusions varied between tasks and between jaw muscle agonists and antagonists, but not in displacement magnitude. There were qualitative differences between participants in the effects of infusion on EMG activity. During hypertonic saline infusion, significant positive correlations were noted between jaw-closing EMG activity and anxiety, fear of medical pain, and PCS scores. CONCLUSION: Noxious stimulation of the temporalis muscle results in changes in jaw muscle activity, which can vary with the task, the muscle, the participant, and some psychological variables.

Brainstem Pain-Control Circuitry Connectivity in Chronic Neuropathic Pain.

Preclinical investigations have suggested that altered functioning of brainstem pain-modulation circuits may be crucial for the maintenance of some chronic pain conditions. While some human psychophysical studies show that patients with chronic pain display altered pain-modulation efficacy, it remains unknown whether brainstem pain-modulation circuits are altered in individuals with chronic pain. The aim of the present investigation was to determine whether, in humans, chronic pain following nerve injury is associated with altered ongoing functioning of the brainstem descending modulation systems. Using resting-state functional magnetic resonance imaging, we found that male and female patients with chronic neuropathic orofacial pain show increased functional connectivity between the rostral ventromedial medulla (RVM) and other brainstem pain-modulatory regions, including the ventrolateral periaqueductal gray (vlPAG) and locus ceruleus (LC). We also identified an increase in RVM functional connectivity with the region that receives orofacial nociceptor afferents, the spinal trigeminal nucleus. In addition, the vlPAG and LC displayed increased functional connectivity strengths with higher brain regions, including the hippocampus, nucleus accumbens, and anterior cingulate cortex, in individuals with chronic pain. These data reveal that chronic pain is associated with altered ongoing functioning within the endogenous pain-modulation network. These changes may underlie enhanced descending facilitation of processing at the primary synapse, resulting in increased nociceptive transmission to higher brain centers. Further, our findings show that higher brain regions interact with the brainstem modulation system differently in chronic pain, possibly reflecting top-down engagement of the circuitry alongside altered reward processing in pain conditions.SIGNIFICANCE STATEMENT Experimental animal models and human psychophysical studies suggest that altered functioning of brainstem pain-modulation systems contributes to the maintenance of chronic pain. However, the function of this circuitry has not yet been explored in humans with chronic pain. In this study, we report that individuals with orofacial neuropathic pain show altered functional connectivity between regions within the brainstem pain-modulation network. We suggest that these changes reflect largely central mechanisms that feed back onto the primary nociceptive synapse and enhance the transfer of noxious information to higher brain regions, thus contributing to the constant perception of pain. Identifying the mechanisms responsible for the maintenance of neuropathic pain is imperative for the development of more efficacious therapies.

The three-axial gyroscope sensor detects the turning point between opening and closing phases of chewing.

Most devices measuring the kinematics of masticatory function are cumbersome to setup and not portable. Data collection would be facilitated, particularly in the elderly, if the device used for the objective measurement of mastication was easily transportable and simple to setup. Accelerometers and gyroscope sensors are lightweight and portable and may be useful alternatives. The definition of the turning point between the opening and closing phases of chewing is important for studies of associations between muscle activity and effects of perturbations. Measures of the mediolateral angle (specifically, the mandibular tilt from the lateral view) allow the detection of the turning point between the opening and closing phases. The aim was to determine whether a three-axial gyroscope sensor can detect the turning point between opening and closing phases of chewing. Fourteen asymptomatic participants chewed gum while the output was recorded from a three-axial gyroscope sensor (Seiko Epson, Japan) attached to the chin and a 6 degree-of-freedom electromagnetic jaw-tracking device (Pollhemus, USA). Bland-Altman plots were used to assess the matching of the recordings made by the three-axial gyroscope sensor and the jaw-tracking device. The turning points between the opening and closing phases of chewing matched closely when recorded by a jaw-tracking device and when using a three-axial gyroscope sensor. A three-axial gyroscope sensor can validly detect the turning point between the opening and closing phases during chewing of gum.

Effect of a brief episode of experimental muscle pain on jaw movement and jaw-muscle activity during chewing.

The aims of this study were to determine whether: (i) the jaw motor system develops a new pattern of jaw movement and/or jaw-muscle activity after resolution of an acute episode of jaw-muscle pain; and (ii) if jaw-muscle activity and jaw-movement features change progressively with repetition of a chewing sequence. Jaw movement and jaw muscle (masseter, anterior temporalis, and digastric) activity were recorded during free and rate-standardized chewing in eight asymptomatic participants (pain infusion group), before and at three time blocks up to 45 min after a single 0.2-ml bolus infusion of 5% hypertonic saline into the right masseter muscle. The same procedure, without infusion, was performed in another eight participants (control group). There were no significant main effects of group on jaw movement and muscle activity, suggesting that there were no persistent post-pain effects on chewing. Across groups, repetitions of free and unstandardized chewing movements were associated with progressive increases in velocity and amplitude of jaw movement and masseter and temporalis electromyographic (EMG) activity. These findings suggest that factors unrelated to pain, such as practice effects, may be playing a role in the changes in jaw movement and jaw-muscle activity observed after resolution of an acute episode of jaw-muscle pain.

Chronic Neuropathic Pain: It's about the Rhythm.

The neural mechanisms underlying the development and maintenance of chronic neuropathic pain remain unclear. Evidence from human investigations suggests that neuropathic pain is associated with altered thalamic burst firing and thalamocortical dysrhythmia. Additionally, experimental animal investigations show that neuropathic pain is associated with altered infra-slow (<0.1 Hz) frequency oscillations within the dorsal horn and somatosensory thalamus. The aim of this investigation was to determine whether, in humans, neuropathic pain was also associated with altered infra-slow oscillations within the ascending "pain" pathway. Using resting-state functional magnetic resonance imaging, we found that individuals with orofacial neuropathic pain have increased infra-slow oscillatory activity throughout the ascending pain pathway, including within the spinal trigeminal nucleus, somatosensory thalamus, thalamic reticular nucleus, and primary somatosensory cortex. Furthermore, these infra-slow oscillations were temporally coupled across these multiple sites and occurred at frequencies similar to calcium waves in activated astrocytes. The region encompassing the spinal trigeminal nucleus also displayed increased regional homogeneity, consistent with a local spread of neural activity by astrocyte activation. In contrast, no increase in oscillatory behavior within the ascending pain pathway occurred during acute noxious stimuli in healthy individuals. These data reveal increased oscillatory activity within the ascending pain pathway that likely underpins increased thalamocortical oscillatory activity, a self-sustaining thalamocortical dysrhythmia, and the constant perception of pain. Significance statement: Chronic neuropathic pain is associated with altered thalamic firing and thalamocortical dysrhythmia. The mechanisms responsible for these changes remain unknown. In this study, we report in individuals with neuropathic pain increased oscillatory neural activity within the ascending pain pathway with evidence that these changes result from altered neural-astrocyte coupling. We propose a series of neural and glial events after nerve injury that result in the generation of altered thalamocortical activity and a persistent neuropathic pain state. Defining the underlying mechanisms responsible for neuropathic pain is critical if we are to develop more effective treatment regimens.

Pain and Personality: Do Individuals with Different Forms of Chronic Pain Exhibit a Mutual Personality?

The role of personality in the experience of chronic pain is a growing field, with endless debate regarding the existence of a "pain personality". This study aims to compare different chronic pain types and consolidate the existence of a common personality. Thirty-two females with chronic orofacial pain and 37 age-matched healthy females were assessed with the Temperament and Character Inventory-Revised. Chronic pain subjects had either trigeminal neuropathy (neuropathic pain) or temporomandibular disorders (nociceptive pain). This study revealed that individuals with different chronic pain types exhibit a mutual personality profile encompassing significantly higher scores in Harm Avoidance and significantly lower scores in Self-Directedness when compared to healthy subjects. In fact, this combination is associated with Cluster C personality disorders. In conclusion, our study reveals that irrespective of type, chronic pain may be associated with Cluster C personality disorders. Indeed, there has never been empirical evidence in the past to suggest that chronic pain as an overall concept is associated with any particular personality disorders. Therefore, a potential future avenue of chronic pain treatment may lie in targeting particular personality aspects and shift the target of pain-relieving treatments from sensory and psychologically state focused to psychologically trait focused.

Anatomical changes at the level of the primary synapse in neuropathic pain: evidence from the spinal trigeminal nucleus.

Accumulated evidence from experimental animal models suggests that neuronal loss within the dorsal horn is involved in the development and/or maintenance of peripheral neuropathic pain. However, to date, no study has specifically investigated whether such neuroanatomical changes also occur at this level in humans. Using brain imaging techniques, we sought to determine whether anatomical changes were present in the spinal trigeminal nucleus in subjects with chronic orofacial neuropathic pain. In 22 subjects with painful trigeminal neuropathy and 44 pain-free controls, voxel-based morphometry of T1-weighted anatomical images and diffusion tensor images were used to assess regional gray matter volume and microstructural changes within the brainstem. In addition, deterministic tractography was used to assess the integrity of ascending pain pathways. Orofacial neuropathic pain was associated with significant regional gray matter volume decreases, fractional anisotropy increases, and mean diffusivity decreases within the spinal trigeminal nucleus, specifically the subnucleus oralis. In addition, tractography revealed no significant differences in diffusivity properties in the root entry zone of the trigeminal nerve, the spinal trigeminal tract, or the ventral trigeminothalamic tracts in painful trigeminal neuropathy subjects compared with controls. These data reveal that chronic neuropathic pain in humans is associated with discrete alterations in the anatomy of the primary synapse. These neuroanatomical changes may be critical for the generation and/or maintenance of pathological pain.

Subtle alterations in brain anatomy may change an individual's personality in chronic pain.

It is well established that gross prefrontal cortex damage can affect an individual's personality. It is also possible that subtle prefrontal cortex changes associated with conditions such as chronic pain, and not detectable until recent advances in human brain imaging, may also result in subtle changes in an individual's personality. In an animal model of chronic neuropathic pain, subtle prefrontal cortex changes including altered basal dendritic length, resulted in altered decision making ability. Using multiple magnetic resonance imaging techniques, we found in humans, although gray matter volume and on-going activity were unaltered, chronic neuropathic pain was associated with reduced free and bound proton movement, indicators of subtle anatomical changes, in the medial prefrontal cortex, anterior cingulate cortex and mediodorsal thalamus. Furthermore, proton spectroscopy revealed an increase in neural integrity in the medial prefrontal cortex in neuropathic pain patients, the degree of which was significantly correlated to the personality temperament of novelty seeking. These data reveal that even subtle changes in prefrontal cortex anatomy may result in a significant change in an individual's personality.