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Artifact reduction (AR) software has been incorporated into some cone-beam computed tomographic (CBCT) systems to reduce the severity of beam hardening (BH) artifacts and improve image quality. This study quantifies BH artifact and evaluates the effectiveness of AR in 2 CBCT systems.Palatal roots of Dent-Alike (Dentsply Sirona, Tulsa, OK) teeth were prepared and root filled with gutta-percha and EndoSequence BC Sealer (Brasseler, Savannah, GA). Six teeth were imaged with and without AR software using the ProMax3D (Planmeca Oy, Helsinki, Finland) and the Pax-i3D (Vatech, Hwaseong-si, South Korea) systems. FSL (FMRIB, Oxford, UK) software was used to quantify the light and dark components of the BH artifact along the tooth root using a specific region of interest approach and an image-wide analysis approach. Statistical analysis was performed using paired t tests and corrected for multiple comparisons with cluster mass correction using a nonparametric statistical analysis to evaluate the differences in the artifact volumes and areas with and without AR.A significant reduction in the light artifact was observed with the Planmeca system (P.05), but no significant differences were observed for either the light or dark artifacts with the Vatech system when AR was applied. There were also significant reductions in the volumes of light and dark artifacts along the entire root length when the AR was applied with the Planmeca system (cluster mass P.05), but no significant differences were observed with the Vatech system.Proprietary AR software is not equally effective in reducing the light and/or dark components of CBCT BH artifacts.

Objective: To assess thermal-sensory thresholds and psychosocial factors in children with Complex Regional Pain Syndrome Type 1 (CRPS-I) compared to healthy children. Methods: We conducted quantitative sensory testing on 34 children with CRPS-I and 56 pain-free children. Warm, cool, heat, and cold stimuli were applied to the forearm. Children with CRPS-I had the protocol administered to the pain site and the contralateral-pain site. Participants completed the self-report Behavior Assessment System for Children. Results: Longer pain durations (>5.1 months) were associated with decreased sensitivity to cold pain on the pain site ( P = .04). Higher pain-intensity ratings were associated with elevated anxiety scores ( P = .03). Anxiety and social stress were associated with warmth sensitivity (both P < .05) on the contralateral-pain site. Conclusions: Pain duration is an important factor in assessing pediatric CRPS-I. Hyposensitivity in the affected limb may emerge due to degeneration of nociceptive nerves. Anxiety may contribute to thermal-sensory perception in childhood CRPS-I.

Supplemental Digital Content is Available in the Text. Cage-lid hanging behavior is impaired by sustained pain in mice and can be used as an ethologically valid and translationally relevant pain outcome measure., The development of new analgesic drugs has been hampered by the inability to translate preclinical findings to humans. This failure is due in part to the weak connection between commonly used pain outcome measures in rodents and the clinical symptoms of chronic pain. Most rodent studies rely on the use of experimenter-evoked measures of pain and assess behavior under ethologically unnatural conditions, which limits the translational potential of preclinical research. Here, we addressed this problem by conducting an unbiased, prospective study of behavioral changes in mice within a natural homecage environment using conventional preclinical pain assays. Unexpectedly, we observed that cage-lid hanging, a species-specific elective behavior, was the only homecage behavior reliably impacted by pain assays. Noxious stimuli reduced hanging behavior in an intensity-dependent manner, and the reduction in hanging could be restored by analgesics. Finally, we developed an automated approach to assess hanging behavior. Collectively, our results indicate that the depression of hanging behavior is a novel, ethologically valid, and translationally relevant pain outcome measure in mice that could facilitate the study of pain and analgesic development.

Chronic pain patients frequently report memory and concentration difficulties. Objective testing in this population points to poor performance on memory and cognitive tests, and increased comorbid anxiety and depression. Recent evidence has suggested convergence between chronic pain and memory deficits onto the hippocampus. The hippocampus consists of heterogenous subfields involved in memory consolidation, behavior regulation, and stress modulation. Despite significant studies outlining hippocampal changes in human and chronic pain animal models, the effect of pain relief on hippocampal abnormalities remains unknown. Trigeminal neuralgia (TN) is a chronic neuropathic pain disorder which is highly amenable to surgical interventions, providing a unique opportunity to investigate the effect of pain relief. This study investigates the effect of pain relief on hippocampal subfields in TN. Anatomical MR images of 61 TN patients were examined before and 6 months after surgery. Treatment responders (n = 47) reported 95% pain relief, whereas non-responders (n = 14) reported 40% change in pain on average. At baseline, patients had smaller hippocampal volumes, compared to controls. After surgery, responders’ hippocampal volumes normalized, largely driven by CA2/3, CA4, and dentate gyrus, which are involved in memory consolidation and neurogenesis. We propose that hippocampal atrophy in TN is pain-driven and successful treatment normalizes such abnormalities. Perspective Chronic pain patients have structural abnormalities in the hippocampus and its subfields. Pain relief normalizes these structural abnormalities and impacts patients in a sex-dependent manner.

Pain is a subjective experience with significant individual differences. Laboratory studies investigating pain thresholds and experimental acute pain have identified structural and functional neural correlates. However, these types of pain stimuli have limited ecological validity to real-life pain experiences. Here, we use an orthodontic procedure—the insertion of an elastomeric separator between teeth—which typically induces mild to moderate pain that peaks within 2 days and lasts several days. We aimed to determine whether the baseline structure and resting-state functional connectivity (rsFC) of key regions along the trigeminal nociceptive and pain modulatory pathways correlate with subsequent peak pain ratings. Twenty-six healthy individuals underwent structural and resting-state functional (rs-fMRI) scanning prior to the placement of a separator between the first and second molars, which was kept in place for five days. Participants recorded pain ratings three times daily on a 100-mm visual analogue scale. Peak pain was not significantly correlated with diffusion metrics of the trigeminal nerve, or grey matter volume of any brain region. Peak pain did, however, positively correlate with baseline rsFC between the thalamus contralateral to the separator and bilateral insula, and negatively correlated with connectivity between the periaqueductal gray (PAG) and core nodes of the default mode network (medial prefrontal and posterior cingulate cortices). The ascending (thalamic) nociceptive and the descending (PAG) pain modulatory pathways at baseline each explained unique variation in peak pain intensity ratings. In sum, pre-interventional functional neural architecture of both systems determined the individual pain experience to a subsequent ecologically valid pain stimulus.

Some forms of chronic pain are thought to be driven and maintained by nociceptive input, which can drive plasticity within nociceptive pathways. We have previously identified abnormalities along the entire nociceptive pathway in chronic myalgic temporomandibular disorders (mTMD), including the trigeminal nerves, brainstem pathways, and in the thalamus and somatosensory cortex. These data suggest that there is a peripheral nociceptive drive in mTMD, but the source of this nociceptive activity remains unknown. Here, our aim was to determine whether structural abnormalities exist in the muscles of mastication of patients with chronic mTMD. Specifically, we tested whether the volume of the temporalis muscle and its tendon-aponeurosis complex (TAC, a structure that dissipates forces in a muscle) in mTMD patients differ compared to age- and sex-matched controls. To do so, we segmented these structures on T1-weighted structural magnetic resonance images. We found that muscle volumes in mTMD were not different to controls. However, the mTMD group had significantly smaller volumes of the bilateral temporalis TAC, and thus a smaller TAC-to-muscle volume ratio. These findings were consistent across 2 independent cohorts of 17 mTMD patients, compared to 17 age- and sex-matched controls. We propose a model where reduced TAC-to-muscle ratio could result in a predisposition to muscle tissue injury. In sum, abnormalities of the temporalis muscles in mTMD supports our hypothesis that chronic mTMD pathophysiology may be related to peripheral nociceptive barrage originating from the muscles of mastication.

Objective In this experimental study, we aimed to determine whether guided music listening (GML) - a music intervention based on models of mood mediation and attention modulation - modulates masticatory muscle activity and awake bruxism in subjects with chronic painful muscular temporomandibular disorders (TMD myalgia, mTMD), a condition causing a significant burden to patients, their families, and healthcare systems. Background Awake bruxism - a stress behavior characterized by clenching of the teeth - is a strong contributor to chronic mTMD. GML modulates psychological stress and motor responses and could thus reduce muscle activity in chronic musculoskeletal conditions, including mTMD. Methods We recorded the electromyographic (EMG) activity in the right masseter of 14 women with chronic (>6 months) mTMD (median [IQR] = 39.5.3 [24.3] years) and 15 pain-free women (median [IQR] = 30.0 [3.5] years) during a GML session, including 3 music (stressful, relaxing, and participants' favorite music) and a no-music (pink noise) control blocks, each lasting 15 minutes. We measured the motor effort of the right masseter relative to the participants' maximum voluntary contraction (MVC), the muscular effort to maintain mandibular posture (EMGposture ), and to produce spontaneous awake bruxism episodes (EMGbruxism ), and the duration and frequency of spontaneous awake bruxism episodes. We tested between-group and within-group (between blocks) differences, as well as the effect of the interaction group by experimental block on these outcome measures. Results In both groups, EMGposture was significantly affected by the interaction group by experimental block (P .05]. EMGbruxism was significantly greater in mTMD participants than controls during the stressful music block [contrast estimate (95% CI): +12.9 (1.6-24.2) %MVC; P = .026). GML did not affect the duration or the frequency of awake bruxism in either group (median [IQR], mTMD: 23.5 [96.7] s, range 1-1300 seconds; Controls: 5.5 [22.5], range 0-246 seconds; P = .108). The frequency of awake bruxism episodes was greater in the mTMD group compared to controls only during the pink noise block (median [IQR], mTMD: 5 [15.3] episodes, range 0-62 episodes; Controls: 1 [3] episode, range 0-27 episodes; P = .046). No significant between-group differences were found in either the overall time spent engaging in awake bruxism (median [IQR], mTMD: 23.5 [96.7] s, range 1-1300 seconds; Controls: 5.5 [22.5], range 0-246 seconds; P = .108), or during each block (all P > .05). Conclusions In subjects with chronic mTMD, relaxing music and the individual's favorite music decreased the muscular effort during spontaneous awake bruxism episodes by 26% and 44% (relative changes), respectively. In contrast, stressful music increases it by about 43%. Because of its positive effects on awake bruxism, GML with selected music could be a promising and non-invasive component of a multimodal approach for the management of chronic mTMD.

Chronic orofacial pain (COFP) disorders are prevalent and debilitating pain conditions affecting the head, neck and face areas. Neuroimaging studies have reported functional and grey matter abnormalities, but not all the studies have reported consistent findings. Identifying convergent abnormalities across COFPs provides a basis for future hypothesis-driven research aimed at elucidating common CNS mechanisms. Here, we perform three coordinate-based meta-analyses according to PRISMA guidelines to elucidate the central mechanisms of orofacial pain disorders. Specifically, we investigated consistent patterns of: (1) brain function to experimental orofacial pain in healthy subjects, (2) structural and (3) functional brain abnormalities in COFP. We computed our coordinate-based meta-analyses using GingerALE. The experimental pain meta-analysis revealed increased brain activity in bilateral thalami, posterior mid-cingulate cortices, and secondary somatosensory cortices, the right posterior parietal cortex extending to the orofacial region of the right primary somatosensory cortex and the right insula, and decreased activity in the right somatomotor regions. The structural COFP meta-analysis identified consistent higher grey matter volume/concentration in the right ventral thalamus and posterior putamen of COFP patients compared to healthy controls. The functional COFP meta-analysis identified a consistent increase in brain activity in the left medial and posterior thalamus and lesser activity in the left posterior insula in COFP, compared to healthy controls. Overall, these findings provide evidence of brain abnormalities in pain-related regions, namely the thalamus and insula, across different COFP disorders. The convergence of thalamic abnormalities in both structure and function suggest a key role for this region in COFP pathophysiology., Highlights • Identifying convergent abnormalities in COFP can elucidate novel therapeutic targets. • Experimental orofacial pain is associated with activity in nociceptive processing brain areas. • Chronic orofacial pain (COFP) is associated with abnormal thalamic activity and grey matter. • Our review highlights the need for more high quality COFP brain imaging studies.

BACKGROUND Many diseases and conditions can disrupt the normal function of the salivary glands, and imaging can be an important tool in the formulation of a diagnosis. With sialography being the imaging modality of choice for obstructive conditions of the major salivary glands, our group has previously demonstrated that cone beam computed tomography (CBCT) sialography offers enhanced visualization of inflammatory changes and obstructions, such as sialoliths and strictures, over plain film sialography.1 However, because ionizing radiation is a concern, optimizing imaging protocols is crucial in order to minimize the radiation dose to the patient while still producing images of high diagnostic quality. OBJECTIVE(S) As a first step in the optimization of a new imaging protocol for CBCT sialography, this study aimed to determine effective dose (E) for a range of exposure parameters using 2 field of view (FOV) sizes for submandibular and parotid gland CBCT sialography. STUDY DESIGN Using a RANDO male phantom, we determined site-specific radiation doses to 25 sites in the head and neck and calculated E across a range of operating kilovoltage peak and milliamperage settings of the J. Morita Veraview X800 (J. Morita Mfg. Corp., Kyoto, Japan). RESULTS The E for the submandibular gland study using an 8 cm (diameter) × 5 cm (height) FOV size ranged from 22.7 to 171.1 µSv, when varied across the unit's allowable kilovoltage peak and milliamperage range. For the parotid gland study using an 8 cm (diameter) × 8 cm (height) FOV size, the E ranged from 21.5 to 160.4 µSv. DISCUSSION/CONCLUSIONS The use of variable FOV sizes for the submandibular and parotid glands may allow reductions in E compared with our earlier work2 and allow us to further optimize sialography imaging protocols for future patients.

The dorsolateral prefrontal cortex (DLPFC) is a functionally and structurally heterogeneous region and a key node of several brain networks, implicated in cognitive, affective, and sensory processing. As such, the DLPFC is commonly activated in experimental pain studies, and shows abnormally increased function in chronic pain populations. Furthermore, several studies have shown that some chronic pains are associated with decreased left DLPFC gray matter and that successful interventions can reverse this structural abnormality. In addition, studies have indicated that noninvasive stimulation of the left DLPFC effectively treats some chronic pains. In this article, we review the neuroimaging literature regarding the role of the DLPFC and its potential as a therapeutic target for chronic pain conditions, including studies showing the involvement of the DLPFC in encoding and modulating acute pain and studies demonstrating the reversal of DLPFC functional and structural abnormalities after successful interventions for chronic pain. We also review studies of noninvasive brain stimulation of the DLPFC showing acute pain modulation and some effectiveness as a treatment for certain chronic pain conditions. We further discuss the network architecture of the DLPFC, and postulate mechanisms by which DLPFC stimulation alleviates chronic pain. Future work testing these mechanisms will allow for more effective therapies. Perspective The structure and function of the DLPFC is abnormal in some chronic pain conditions. Upon successful resolution of pain, these abnormalities are reversed. Understanding the underlying mechanisms and the role of this region can lead to the development of an effective therapeutic target for some chronic pain conditions.

Medial temporal lobe activity is investigated in meta-analyses of experimental and chronic pain. Abnormal hippocampal connectivity is found in patients with chronic low back pain., The orofacial region is psychologically important, given that it serves fundamental and important biological purposes. Chronic orofacial pain disorders affect the head and neck region. Although some have clear peripheral etiologies, eg, classic trigeminal neuralgia, others do not have a clear etiology (eg, muscular temporomandibular disorders). However, these disorders provide a unique opportunity in terms of elucidating the neural mechanisms of these chronic pain conditions: both the peripheral and central nervous systems can be simultaneously imaged. Diffusion-weighted imaging and diffusion tensor imaging have provided a method to essentially perform in vivo white matter dissections in humans, and to elucidate abnormal structure related to clinical correlates in disorders, such as chronic orofacial pains. Notably, the trigeminal nerve anatomy and architecture can be captured using diffusion imaging. Here, we review the trigeminal somatosensory pathways, diffusion-weighted imaging methods, and how these have contributed to our understanding of the neural mechanisms of chronic pain disorders affecting the trigeminal system. We also discuss novel findings indicating the potential for trigeminal nerve diffusion imaging to develop diagnostic and precision medicine biomarkers for trigeminal neuralgia. In sum, diffusion imaging serves both an important basic science purpose in identifying pain mechanisms, but is also a clinically powerful tool that can be used to improve treatment outcomes.

Objective To evaluate how physical photostimulable phosphor (PSP) plate artifacts, such as those created by scratches, phosphor degradation, and surface peeling, affect the radiologic interpretation of periapical inflammatory disease. Study Design A novel technique was developed to digitally superimpose 25 real PSP artifact masks over 100 clinical complementary metal oxide semiconductor (CMOS) periapical images with known radiologic interpretations. These images were presented to 25 general dentists, who were asked to state their radiologic interpretations, their confidence in their interpretations, and their opinions on whether the plates should be discarded. Statistical analyses were conducted by using random intercept mixed models for repeated measures and χ2 tests of the pooled data. Results No statistically significant adverse effect on interpretation was seen, even at severe artifact levels. There was a statistically significant decrease in the clinicians’ confidence and an increase in discard proportions when interpreting images with severe PSP plate artifacts (P Conclusions Although diagnostic efficacy was unaffected, clinicians’ confidence decreased and proportionally more clinicians opted to discard sensors when interpreting images with severe artifacts. Future studies on the effects of artifacts on the efficacy of diagnosis of other dental diseases are recommended. Ultimately, these results can guide recommendations for PSP plate quality assurance.

Recent neuroimaging studies implicate the medial temporal lobe (MTL) in nociception and pain modulation. Here, we aim to identify which subregions of the MTL are involved in human pain and to test its connectivity in a cohort of chronic low-back pain patients (CBP). We conducted 2 coordinate-based meta-analyses to determine which regions within the MTL showed consistent spatial patterns of functional activation (1) in response to experimental pain in healthy participants and (2) in chronic pain compared with healthy participants. We followed PRISMA guidelines and performed activation likelihood estimate (ALE) meta-analyses. The first meta-analysis revealed consistent activation in the right anterior hippocampus (right antHC), parahippocampal gyrus, and amygdala. The second meta-analysis revealed consistently less activation in patients' right antHC, compared with healthy participants. We then conducted a seed-to-voxel resting state functional connectivity of the right antHC seed with the rest of the brain in 77 CBP and 79 age-matched healthy participants. We found that CBP had significantly weaker antHC functional connectivity to the medial prefrontal cortex compared with healthy participants. Taken together, these data indicate that the antHC has abnormally lower activity in chronic pain and reduced connectivity to the medial prefrontal cortex in CBP. Future studies should investigate the specific role of the antHC in the development and management of chronic pain.

Supplemental Digital Content is Available in the Text., Introduction: Multimodal characterisation with questionnaires, Quantitative Sensory Testing (QST), and neuroimaging will improve understanding of neuropathic pain (NeuP) in adolescents. Magnetic resonance imaging (MRI) data in adolescents with NeuP are limited, and the perceived practical or ethical burden of scanning may represent a barrier to research. Objective: To determine the feasibility of MRI scanning in adolescents with moderate–severe NeuP, with respect to consent rate, postscan acceptability, and data quality. Methods: This prospective cohort study evaluating questionnaires and QST recruited adolescents aged 10 to 18 years with clinically diagnosed NeuP from a tertiary clinic. Eligible adolescents aged 11 years and older could additionally agree/decline an MRI scan. After the scan, families rated discomfort, perceived risk, and acceptability of current and future MRI scans (0–10 numerical rating scales). Head motion during scanning was compared with healthy controls to assess data quality. Results: Thirty-four families agreed to MRI (72% recruitment), and 21 adolescents with moderate–severe pain (average last week 6.7 ± 1.7; mean ± SD) and with neuropathic QST profiles were scanned. Three adolescents reported positional or noise-related discomfort during scanning. Perceived risk was low, and acceptability of the current scan was high for parents (range [median]: 7 to 10/10 [10]) and adolescents (8–10/10 [10]). Willingness to undergo a future research scan was high for parents (7–10/10 [10]) and adolescents (5–10/10 [10]) and did not differ from future scans for clinical purposes. Mean head motion during resting state functional MRI did not differ from control adolescents. Conclusion: Research MRI is feasible and acceptable for many adolescents with moderate–severe NeuP.

Background The diagnosis of temporomandibular disorders (TMDs), specifically TMD myalgia, can be challenging. Although the anatomy of the jaw muscles has been extensively characterized, a structural difference in TMD-myalgia individuals has never been demonstrated. Tendons are a highly specialized tissue with a predominately mechanical function. Collagen fibrils, the main contributor to tendon mechanical properties, begin macroscopic failure at 8% to 10% strain. The characterization of tendon/muscle abnormalities in individuals with chronic, painful TMD myalgia will lay the groundwork for utilizing noninvasive magnetic resonance imaging (MRI) for screening and objective monitoring of patients with TMD myalgia. A structural marker unique to TMD myalgia will aid in its diagnosis and treatment. Objective(s) This study aimed to determine differences in the tendon/muscle volume ratio of the temporalis muscle in patients with TMD myalgia compared with age-/gender-matched controls without facial pain. Study Design This was a retrospective, observational study of the temporalis muscle and tendon on MRI images. The comparison between groups was based on a voxel-based morphometry of anatomic T1-weighted MRI images and analyzed for differences in the tendon/muscle volume ratio. The study included at least 14 patients per group to detect a 5% difference in tendon/muscle volume ratio. An intraclass correlation coefficient was used to evaluate the intrarater test–retest reliability. General linear models were used to test whether the outcome measures (muscle/tendon volume, muscle/tendon T1 signal intensity, tendon/muscle ratio) are different between groups. Results Our pilot data demonstrated similar muscle volumes but significantly smaller tendon volumes and signal intensity when comparing patients with TMD myalgia with healthy controls (P Discussion/Conclusions Preliminary data suggest that chronic TMD myalgia may be associated with structural abnormalities of the temporalis tendon. Should the temporalis tendon/muscle volume ratio prove to be a reliable marker, this metric may be used to evaluate different treatment modalities in a noninvasive manner.

The field of human pain neuroimaging has exploded in the last two decades. During this time, the broader neuroimaging community has continued to investigate and refine methods. Another key to progress is exchange with clinicians and pain scientists working with other model systems and approaches. These collaborative efforts require that non-imagers be able to evaluate and assess the evidence provided in these papers. Likewise, new trainees must design rigorous and reliable pain imaging experiments. Here, we provide a guideline for designing, reading, evaluating, analyzing, and reporting results of a pain neuroimaging experiment, with a focus on functional and structural MRI. We focus in particular on considerations that are unique to neuroimaging studies of pain in humans, including study design and analysis, inferences that can be drawn from these studies, and the strengths and limitations of the approach. This article provides an overview of the concepts and considerations of structural and functional MRI neuroimaging studies. The primer is written for those who are not familiar with brain imaging. We review key concepts related to recruitment and study sample, experimental design, data analysis and data interpretation. [Abstract copyright: Copyright © 2018. Published by Elsevier Inc.]

Background Approximately 30% of patients with major depressive disorder develop treatment-nonresponsive depression (TNRD); novel interventions targeting the substrates of this illness population are desperately needed. Convergent evidence from lesion, stimulation, connectivity, and functional neuroimaging studies implicates the frontopolar cortex (FPC) as a particularly important region in TNRD pathophysiology; regions functionally connected to the FPC, once identified, could present favorable targets for novel brain stimulation treatments. Methods We recently published a parcellation of the FPC based on diffusion tensor imaging data, identifying distinct medial and lateral subregions. Here, we applied this parcellation to resting-state functional magnetic resonance imaging scans obtained in 56 patients with TNRD and 56 matched healthy control subjects. Results In patients, the medial FPC showed reduced connectivity to the anterior midcingulate cortex and insula. The left lateral FPC showed reduced connectivity to the right lateral orbitofrontal cortex and increased connectivity to the fusiform gyri. In addition, TNRD symptom severity correlated significantly with connectivity of the left lateral FPC subregion to a medial orbitofrontal cortex region of the classical reward network. Conclusions Taken together, these findings suggest that changes in FPC subregion connectivity may underlie several dimensions of TNRD pathology, including changes in reward/positive valence, nonreward/negative valence, and cognitive control domains. Nodes of functional networks showing abnormal connectivity to the FPC could be useful in generating novel candidates for therapeutic brain stimulation in TNRD.

Repeated exposure to pain can result in sensitization of the central nervous system, enhancing subsequent pain and potentially leading to chronicity. The ability to reverse this sensitization in a top-down manner would be of tremendous clinical benefit, but the degree that this can be accomplished volitionally remains unknown. Here we investigated whether a brief (~5 min) cognitive-behavioural intervention could modify pain perception and reduce central sensitization (as reflected by secondary hyperalgesia). In each of 8 sessions, 2 groups of healthy human subjects received a series of painful thermal stimuli that resulted in secondary hyperalgesia. One group (regulate) was given brief pain-focused cognitive training at each session, while the other group (control) received a non-pain-focused intervention. The intervention selectively reduced pain unpleasantness but not pain intensity in the regulate group. Furthermore, secondary hyperalgesia was significantly reduced in the regulate group compared with the control group. Reduction in secondary hyperalgesia was associated with reduced pain catastrophizing, suggesting that changes in central sensitization are related to changes in pain-related cognitions. Thus, we demonstrate that central sensitization can be modified volitionally by altering pain-related thoughts.

It is well established that there is individual variability in pain and temperature sensitivity. Functional brain imaging studies have found that interindividual heat pain variability correlates with brain activity in sensory and pain modulation areas. Thus, it is possible that these individual differences are associated with variability in gray matter thickness of cortical regions involved in thermoreception and pain. To test this, we investigated the relationship between thermal thresholds and cortical thickness in 80 healthy subjects. Subjects underwent a psychophysical session to determine their cool detection (CD), warm detection (WD), cold pain (CP), and heat pain (HP) threshold. A high-resolution structural magnetic resonance imaging scan was acquired for each subject. We correlated each threshold measure to cortical thickness of regions associated with thermoreception and pain. The mean (± SD) thresholds were 30.7 °C (± 0.8) for CD, 33.8 °C (± 0.7) for WD, 11.7 °C (± 9.7) for CP, and 45.3 °C (± 2.8) for HP. The brain gray matter analysis revealed a strong correlation between greater thermal and pain sensitivity and cortical thickening of the primary somatosensory cortex. Additionally, greater sensitivity to cool stimuli correlated with cortical thickening in the paracentral lobule, and greater WD correlated with cortical thinning in the anterior midcingulate cortex. We also found that greater HP sensitivity correlated with thickening in the posterior midcingulate cortex and the orbitofrontal cortex. These cortical gray matter correlates of thermal and pain sensitivity provide a neural basis for individual differences in thermal sensitivity.

Trigeminal neuropathic pain (TNP) and temporomandibular disorders (TMD) are thought to have fundamentally different etiologies. It has been proposed that TNP arises through damage to, or pressure on, somatosensory afferents in the trigeminal nerve, whereas TMD results primarily from peripheral nociceptor activation. Because some reports suggest that neuropathic pain is associated with changes in brain anatomy, it is possible that TNP is maintained by changes in higher brain structures, whereas TMD is not. The aim of this investigation is to determine whether changes in regional brain anatomy and biochemistry occur in both conditions. Twenty-one TNP subjects, 20 TMD subjects, and 36 healthy controls were recruited. Voxel-based morphometry of T1-weighted anatomical images revealed no significant regional gray matter volume change in TMD patients. In contrast, gray matter volume of TNP patients was reduced in the primary somatosensory cortex, anterior insula, putamen, nucleus accumbens, and the thalamus, whereas gray matter volume was increased in the posterior insula. The thalamic volume decrease was only seen in the TNP patients classified as having trigeminal neuropathy but not those with trigeminal neuralgia. Furthermore, in trigeminal neuropathy patients, magnetic resonance spectroscopy revealed a significant reduction in the N-acetylaspartate/creatine ratio, a biochemical marker of neural viability, in the region of thalamic volume loss. The data suggest that the pathogenesis underlying neuropathic and non-neuropathic pain conditions are fundamentally different and that neuropathic pain conditions that result from peripheral injuries may be generated and/or maintained by structural changes in regions such as the thalamus.