Symptom severity in burning mouth syndrome associates with psychological factors.

Burning mouth syndrome (BMS) patients are psychologically distressed, but whether this associates with symptom severity is unclear. The aim was to investigate the association of psychological factors with pain intensity and interference in BMS. Fifty-two women (mean age 63.1, SD 10.9) with BMS participated. Pain intensity and interference data were collected using 2-week pain diaries. Psychological factors were evaluated using Depression Scale (DEPS), Pain Anxiety Symptom Scale (PASS) and Pain Vigilance and Awareness Questionnaire (PVAQ). The local ethical committee approved the study. Patients were divided into groups based on pain severity distribution tertiles: low intensity (NRS ≤ 3.7) or interference (NRS ≤ 2.9) (tertiles 1-2, n = 35) and moderate to intense intensity (NRS > 3.7) or interference (>2.9) (tertile 3, n = 17). T test, Wilcoxon's test and Pearson's correlation coefficient were used in the analyses. Patients in the highest intensity and interference tertiles reported more depression (P = .0247 and P = .0169) and pain anxiety symptoms (P = .0359 and P = .0293), and were more preoccupied with pain (P = .0004 and P = .0003) than patients in the low intensity and interference groups. The score of the pain vigilance questionnaire correlated significantly with pain intensity (r = .366, P = .009) and interference (r = .482, P = .009). Depression (r = .399, P = .003) and pain anxiety symptoms (r = .452, P = .001) correlated with pain interference. Symptom severity in BMS associates with symptoms of psychological distress emphasising the need to develop multidimensional diagnostics for the assessment of BMS pain.

Up-regulation of IL-1ß and sPLA2-III in the medial prefrontal cortex contributes to orofacial and somatic hyperalgesia induced by malocclusion via glial-neuron crosstalk.

The medial prefrontal cortex (mPFC) has been identified as a key brain region involved in the modulation of chronic pain. Our recent study demonstrated that unilateral anterior crossbite (UAC) developed the comorbidity model of temporomandibular disorders (TMD) and fibromyalgia syndrome (FMS), which was characterized by both orofacial and somatic hyperalgesia. In the present study, UAC rats exhibited significant changes in gene expression in the mPFC. Enrichment analysis revealed that the significantly involved pathways were cytokines-cytokine receptor interaction and immune response. The expression of group III secretory phospholipase A2 (sPLA2-III) was significantly increased in the mPFC of UAC rats. Silencing sPLA2-III expression in the mPFC blocked the orofacial and somatic hyperalgesia. Immunofluorescence showed that sPLA2-III was mainly localized in neurons. The expression of interleukin-1ß (IL-1ß) in the mPFC significantly increased after UAC. Injection of IL-1ß antibody into the mPFC blocked orofacial and somatic hyperalgesia. IL-1ß was mainly localized in microglia cells. Furthermore, injection of IL-1ß antibody significantly reduced the expression of sPLA2-III. These results indicate that neuroinflammatory cascade responses induced by glial-neuron crosstalk in the mPFC may contribute to the development of TMD and FMS comorbidity, and IL-1ß and sPLA2-III are identified as novel potential therapeutic targets for the treatment of chronic pain in the comorbidity of TMD and FMS.

Pain Relief Following Selective Tibial Neurotomy for Spastic Equinus Foot Secondary to Stroke and Traumatic Brain Injury.

OBJECTIVE: Selective tibial neurotomy (STN) has been indicated for spastic equinus foot (SEF); however, the impact of this procedure on quality of life and activities of daily living has not been evaluated in detail. This study aimed to evaluate the surgical outcomes of STN and its effect on SEF accompanied by pain. METHODS: We evaluated 26 patients (mean age: 59.6 ± 15.2 years; 14 men and 12 women) who underwent STN for SEF, 10 of whom complained of spontaneous pain preoperatively. We used the following scales for clinical evaluation: the Modified Ashworth Scale, Medical Research Council (MRC), 10-m walking test, Functional Independence Measure, and numeric rating scale for pain. These scales were evaluated preoperatively and postoperatively. Differences in clinical characteristics were compared between the 10 patients with pain and the 16 patients without pain. RESULTS: Significant differences were observed in all evaluation scale scores except for the Functional Independence Measure, and no serious adverse events were reported. Pain intensity was significantly improved from 6.4 ± 2.0 to 2.7 ± 2.3 (P < 0.05). An analysis showed that the preoperative mean Medical Research Council score of ankle movement was significantly lower in patients with pain but recovered to the same level postoperatively at the 6-month follow-up. CONCLUSIONS: Our study showed significant improvements in spasticity and its associated symptoms, and STN effectively addressed spastic pain and motor weakness. Among various treatment modalities, STN may be positively indicated for patients with spastic pain in the lower leg.

The Case for Comorbid Myofascial Pain-A Qualitative Review.

Myofascial pain syndrome is widely considered to be among the most prevalent pain conditions, both in the community and in specialized pain clinics. While myofascial pain often arises in otherwise healthy individuals, evidence is mounting that its prevalence may be even higher in individuals with various comorbidities. Comorbid myofascial pain has been observed in a wide variety of medical conditions, including malignant tumors, osteoarthritis, neurological conditions, and mental health conditions. Here, we review the evidence of comorbid myofascial pain and discuss the diagnostic and therapeutic implications of its recognition.

A Central Amygdala Input to the Parafascicular Nucleus Controls Comorbid Pain in Depression.

While comorbid pain in depression (CP) occurs at a high rate worldwide, the neural connections underlying the core symptoms of CP have yet to be elucidated. Here, we define a pathway whereby GABAergic neurons from the central nucleus of the amygdala (GABACeA) project to glutamatergic neurons in the parafascicular nucleus (GluPF). These GluPF neurons relay directly to neurons in the second somatosensory cortex (S2), a well-known area involved in pain signal processing. Enhanced inhibition of the GABACeA→GluPF→S2 pathway is found in mice exhibiting CP symptoms. Reversing this pathway using chemogenetic or optogenetic approaches alleviates CP symptoms. Together, the current study demonstrates the putative importance of the GABACeA→GluPF→S2 pathway in controlling at least some aspects of CP.

Neuropathic Ocular Pain due to Dry Eye is Associated with Multiple Comorbid Chronic Pain Syndromes.

UNLABELLED: Recent data show that dry eye (DE) susceptibility and other chronic pain syndromes (CPS) such as chronic widespread pain, irritable bowel syndrome, and pelvic pain, might share common heritable factors. Previously, we showed that DE patients described more severe symptoms and tended to report features of neuropathic ocular pain (NOP). We hypothesized that patients with a greater number of CPS would have a different DE phenotype compared with those with fewer CPS. We recruited a cohort of 154 DE patients from the Miami Veterans Affairs Hospital and defined high and low CPS groups using cluster analysis. In addition to worse nonocular pain complaints and higher post-traumatic stress disorder and depression scores (P < .01), we found that the high CPS group reported more severe neuropathic type DE symptoms compared with the low CPS group, including worse ocular pain assessed via 3 different pain scales (P < .05), with similar objective corneal DE signs. To our knowledge, this was the first study to show that DE patients who manifest a greater number of comorbid CPS reported more severe DE symptoms and features of NOP. These findings provided further evidence that NOP might represent a central pain disorder, and that shared mechanistic factors might underlie vulnerability to some forms of DE and other comorbid CPS. PERSPECTIVE: DE patients reported more frequent CPS (high CPS group) and reported worse DE symptoms and ocular and nonocular pain scores. The high CPS group reported symptoms of NOP that share causal genetic factors with comorbid CPS. These results imply that an NOP evaluation and treatment should be considered for DE patients.

Impact of Alprazolam on Comorbid Pain and Knee Functions in Total Knee Arthroplasty Patients Diagnosed with Anxiety and Depression.

PURPOSE: Studies report 19-33% postoperative moderate-severe pain and dissatisfaction in uncomplicated total knee arthroplasty (TKA), even after 1 year. High rates of undiagnosed depression and anxiety may have a strong impact on these unfavourable outcomes. Here we aimed to investigate the efficacy of alprazolam on postoperative analgesic use and knee functions. METHODS: Seventy-six patients with a mean age of 65 ± 9.3 years (range 46-80) diagnosed with mild-moderate anxiety or depression according to the Hamilton anxiety scale (HAS) and Beck Depression Inventory (BDI) that underwent TKA were evaluated in the study. Group 1 patients were subjected to alprazolam treatment in addition to an analgesic/antiinflammatory drug, whereas Group 2 consisted of patients receiving only the standard postoperative pain management protocol. Visual analog scale (VAS) and postoperative analgesic use (g/day) were calculated to evaluate the magnitude of pain experienced. Preoperative and postoperative knee functions were assessed from the patients' Knee Society Score and Knee Society Functional Score records. RESULTS: A positive correlation was found between the preoperative HAS, BDI, and total postoperative analgesic use in both groups. Although the decrease in VAS was significant in both groups, postoperative analgesic need (4.25 ± 0.30 g) in Group 1 was less compared to Group 2 (4.81 ± 0.41 g) (p=0.01). The mean change in postoperative (1 month) Knee Society Score and Knee Society Functional Score were also significantly improved in Group1 compared to Group 2. CONCLUSION: Alprazolam can reduce postoperative analgesic use and improve knee functions by reducing the pain threshold, and enhancing overall mood via its antidepressive and anxiolytic properties in patients undergoing TKA diagnosed with mild-moderate anxiety/depression.

Acupuncture, counselling or usual care for depression and comorbid pain: secondary analysis of a randomised controlled trial.

BACKGROUND: Depression with comorbid pain is associated with a poor response to various treatments. The objective in this secondary analysis was to determine whether patients reporting pain have different depression and pain outcomes over time in response to acupuncture, counselling or usual care. METHODS: Self-reported ratings of depression and pain from 755 patients in a pragmatic randomised controlled trial of acupuncture (302) or counselling (302) compared to usual care alone (151) are described and analysed using a series of regression models and analysis of covariance. Patient-reported outcomes of Patient Health Questionnaire (PHQ)-9 for depression, SF36 bodily pain and EQ-5D, all at baseline, 3, 6, 9 and 12 months. RESULTS: At baseline, 755 patients reported EQ-5D pain categories; 384 (50.9%) reported moderate-to-extreme pain. Controlling for baseline depression, a linear regression model showed that the presence of pain at baseline was associated with poorer depression outcomes at 3 months mean difference=-1.16, (95% CI 0.12 to 2.2). Participants with moderate-to-extreme pain at baseline did better at 3 months if they received acupuncture (mean reduction in Patient Health Questionnaire 9 (PHQ-9) from baseline=6.0, 95% CI 5.0 to 7.1 and a mean reduction in SF-36 bodily pain=11.2, (95% CI 7.1 to 15.2) compared to improvements for those who received counselling (4.3, 95% CI 3.3 to 5.4; 7.6, 95% CI 3.6 to 11.6) or usual care (2.7, 95% CI 1.50 to 4.0: 7.2, 95% CI 2.3 to 12.1). In comparison, no notable differences were seen between treatment arms within the no pain comparator group. CONCLUSIONS: Patients with depression and pain at baseline recovered less well from treatment over 3 months than those with depression and no pain. Reductions in both depression and pain were most marked in the acupuncture group, followed by the counselling group and then the usual care group.

A clinically relevant animal model of temporomandibular disorder and irritable bowel syndrome comorbidity.

UNLABELLED: Temporomandibular disorder and irritable bowel syndrome are comorbid functional chronic pain disorders of unknown etiology that are triggered/exacerbated by stress. Here we present baseline phenotypic characterization of a novel animal model to gain insight into the underlying mechanisms that contribute to such comorbid pain conditions. In this model, chronic visceral hypersensitivity, a defining symptom of irritable bowel syndrome, is dependent on 3 factors: estradiol, existing chronic somatic pain, and stress. In ovariectomized rats, estradiol replacement followed by craniofacial muscle injury and stress induced visceral hypersensitivity that persisted for months. Omission of any 1 factor resulted in a transient (1 week) visceral hypersensitivity from stress alone or no hypersensitivity (no inflammation or estradiol). Maintenance of visceral hypersensitivity was estradiol dependent, resolving when estradiol replacement ceased. Referred cutaneous hypersensitivity was concurrent with visceral hypersensitivity. Increased spinal Fos expression suggests induction of central sensitization. These data demonstrate the development and maintenance of visceral hypersensitivity in estradiol-replaced animals following distal somatic injury and stress that mimics some characteristics reported in patients with temporomandibular disorder and comorbid irritable bowel syndrome. This new animal model is a powerful experimental tool that can be employed to gain further mechanistic insight into overlapping pain conditions. PERSPECTIVE: The majority of patients with temporomandibular disorder report symptoms consistent with irritable bowel syndrome. Stress and female prevalence are common to both conditions. In a new experimental paradigm in ovariectomized rats with estradiol replacement, masseter inflammation followed by stress induces visceral hypersensitivity that persists for months, modeling these comorbid pain conditions.

Multisystem dysregulation in painful temporomandibular disorders.

UNLABELLED: Multiple physiological and psychological regulatory domains may contribute to the pathophysiology of pain in temporomandibular disorder (TMD) and other bodily pain conditions. The purpose of this study was to evaluate the relationship between multisystem dysregulation and the presence of TMD pain, as well as the presence of different numbers of comorbid pain conditions in TMD. Secondary data analysis was conducted in 131 non-TMD (without comorbid pain) controls, 14 TMD subjects without comorbid pain, 78 TMD subjects with 1 comorbid pain, and 67 TMD subjects with multiple comorbid pain conditions who participated in a TMD genetic study. Twenty markers from sensory, autonomic, inflammatory, and psychological domains were evaluated. The results revealed that 1) overall dysregulation in multiple system domains (OR [odds ratio] = 1.6, 95% confidence interval [CI] = 1.4-1.8), particularly in the sensory (OR = 1.9, 95% CI = 1.3-2.9) and the psychological (OR = 2.1, 95% CI = 2.1-2.7) domains, were associated with increased likelihood of being a painful TMD case; and 2) dysregulations in individual system domains were selectively associated with the increased odds of being a TMD case with different levels of comorbid persistent pain conditions. These outcomes indicate that heterogeneous multisystem dysregulations may exist in painful TMD subgroups, and multidimensional physiological and psychological assessments can provide important information regarding pathophysiology, diagnosis, and management of pain in TMD patients. PERSPECTIVE: The concurrent assessment of multiple physiological and psychological systems is critical to our understanding of the pathophysiological processes that contribute to painful TMD and associated comorbid conditions, which will ultimately guide and inform appropriate treatment strategies that address the multisystem dysregulation associated with complex and common persistent pain conditions.