Health-related quality of life in patients with chronic orofacial pain compared with other chronic pain patients.

BACKGROUND: Health-related quality of life (HRQoL) of orofacial pain patients is lower than that of the general population and impaired in multiple dimensions. The aim of the present study was to investigate HRQoL of orofacial pain patients in comparison with patients suffering from other chronic pain disorders. MATERIALS AND METHODS: One hundred and fifty-one tertiary care facial pain patients (mean age, 50 years; standard deviation [SD], 15; 119 females), were compared with 312 other non-cancer chronic pain patients (mean age, 46 years; SD, 13; 204 women), recruited from three multidisciplinary pain clinics in Finland. The groups were compared using the 15D, and pain-related measures such as pain interference, pain acceptance, anxiety, depression, and sleep. Statistical comparisons between groups were done using t test, χ2 test, or analysis of covariance. Multivariate linear regression analysis was used to study whether pain-related aspects influencing HRQoL are similar between the patient groups. RESULTS: The 15D score was significantly higher in facial pain patients (0.823; SD, 0.114) indicating better HRQoL in comparison with other chronic pain patients (0.732; SD, 0.107) (p < .001). The 15D profiles of studied populations resembled each other but orofacial pain patients showed significantly higher scores for most individual 15D dimensions. Dimensions regarding discomfort and symptoms and sleep were most affected in both groups. Orofacial pain patients showed less psychosocial disability and better acceptance of their pain. Pain acceptance was a weaker explanatory factor of HRQoL in orofacial pain patients. CONCLUSION: Compared to other non-cancer chronic pain, chronic pain in the orofacial area causes less impairment in HRQoL. Orofacial pain patients showed less psychosocial disability and better pain acceptance.

Developing a research diagnostic criteria for burning mouth syndrome: Results from an international Delphi process.

OBJECTIVE: To develop a beta version of a preliminary set of empirically derived research diagnostic criteria (RDC) for burning mouth syndrome (BMS) through expert consensus, which can then be taken into a test period before publication of a final RDC/BMS. DESIGN: A 6 round Delphi process with twelve experts in the field of BMS was used. The first round formed a focus group during which the purpose of the RDC and the definition of BMS was agreed upon, as well as the structure and contents. The remaining rounds were carried out virtually via email to achieve a consensus of the beta version of the RDC/BMS. RESULTS: The definition of BMS was agreed to be 'an intraoral burning or dysaesthetic sensation, recurring daily for more than 2 hours per day over more than 3 months, without evident causative lesions on clinical examination and investigation'. The RDC was based upon the already developed and validated RDC/TMD and formed three main parts: patient self-report; examination; and psychosocial self-report. A fourth additional part was also developed listing aspirational biomarkers which could be used as part of the BMS diagnosis where available, or to inform future research. CONCLUSION: This Delphi process has created a beta version of an RDC for use with BMS. This will allow future clinical research within BMS to be carried out to a higher standard, ensuring only patients with true BMS are included. Further validation studies will be required alongside refinement of the RDC as trialling progresses.

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.

The impact of chronic orofacial pain on health-related quality of life.

Background and aims Health-related quality of life (HRQoL) assessments have been widely used in pain medicine as they are able to reflect the subjective and multidimensional nature of chronic pain. Studies have shown a consistent impairment in HRQoL in different chronic pain conditions. However, it is not known whether HRQoL is impaired in chronic orofacial pain (OFP). The generic 15D HRQoL instrument has been shown to fare as well as or better than other generic HRQoL instruments in the study of chronic pain. The aim was to investigate HRQoL in patients with chronic OFP using the generic 15D HRQoL instrument. The validity of the instrument was tested by studying the association of the 15D data with pain interference. Methods One hundred fifty-one patients (mean age 50 years, SD 15 years, 119 females) were recruited from three tertiary facial pain clinics. HRQoL data of the participants were contrasted with that of an age- and gender- standardized sample of general population by comparing the mean 15D scores and profiles. The data for the general population came from the National Health 2011 Survey representing Finnish population aged 18 years and older. Pain interference was assessed using Brief Pain Inventory. Based on pain interference distribution the participants were divided into tertiles. Statistical comparison between patient and population HRQoL values were performed using Monte-Carlo-type simulations. Statistical significance for the hypothesis of linearity was evaluated by using generalized linear models. Results The mean 15D score of OFP patients (0.824, SD 0.113) was statistically significantly lower than that of the age- and gender-standardized general population (0.929, SD 0.019) (p < 0.001). The difference between the patients and the general population was also clinically important, i.e. over the minimum clinically important difference in the 15D score. All mean 15D dimension values were significantly lower compared with the general population values (p < 0.001 for all dimensions). The largest differences were seen in the dimensions of discomfort and symptoms (0.418, SD 0.222 vs. 0.816, SD 0.027), sleeping (0.693, SD 0.258 vs. 0.838, SD 0.029), and vitality (0.702, SD 0.221 vs. 0.884 SD 0.026). There was a statistically significant linear decrease in the 15D dimension values (p < 0.001) with increasing pain interference. The greatest differences were found on the dimensions of discomfort and symptoms, sleeping and vitality. Conclusions HRQoL is significantly impaired in patients with chronic OFP. A decrease in the 15D dimension values with increasing pain interference indicated convergent validity between 15D and pain interference. Implications The findings suggest that 15D is an appropriate instrument for use in the assessment of HRQoL in OFP patients. By showing the usefulness of the 15D, the present study may encourage further use of generic HRQoL assessments in the study of chronic OFP, and contribute e.g. to the implementation of HRQoL as one of the core outcome measures in future treatment studies on chronic OFP.

World Workshop in Oral Medicine VII: Reporting of IMMPACT-recommended outcome domains in randomized controlled trials of burning mouth syndrome: A systematic review.

OBJECTIVES: To determine the frequency of use of the core outcome domains published by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) in burning mouth syndrome (BMS) randomized controlled trials (RCTs). METHODS: This systematic review, conducted as part of the World Workshop on Oral Medicine VII (WWOM VII), was performed by searching the literature for studies published in PubMed, Web of Science, PsycINFO, Cochrane Database/Cochrane Central, and Google Scholar from January 1994 (when the first BMS definition came out) through October 2017. RESULTS: A total of 36 RCTs (n = 2,175 study participants) were included and analyzed. The overall reporting of the IMMPACT core and supplemental outcome domains was low even after the publication of the IMMPACT consensus papers in 2003 and 2005 (mean before IMMPACT consensus publication = 2.6 out of 6; mean after IMMPACT publication = 3.8 out of 6). Use of validated assessment tools recommended by the IMMPACT consensus was scarce (1.9 out of 6). None of the RCTs reviewed cited the IMMPACT consensus papers. CONCLUSIONS: The underreporting of IMMPACT outcome domains in BMS RCTs is significant. Raising awareness regarding the existence of standardized outcome domains in chronic pain research is essential to ensure more accurate, comparable, and consistent interpretation of RCT findings that can be clinically translatable.

Neurophysiology and genetics of burning mouth syndrome.

BACKGROUND AND AIMS: Neuropathic mechanisms are involved in burning mouth syndrome (BMS), and variation of the dopamine D2 receptor (DRD2) gene contributes to experimental pain perception. We investigated whether neurophysiologic findings differ in BMS patients compared to healthy controls, and whether 957C>T polymorphism of the DRD2 gene influences thermal sensitivity or pain experience in BMS. METHODS: Forty-five BMS patients (43 women), mean age 62.5 years, and 32 healthy controls (30 women), mean age 64.8 years, participated. Patients estimated pain intensity, interference, suffering and sleep with Numeric Rating Scale. Blink reflex tests of the supraorbital (SON), mental (MN) and lingual (LN) nerves, and thermal quantitative sensory testing were done. The results were analysed with ANOVA. DRD2 gene 957C>T polymorphism was determined in 31 patients, and its effects on neurophysiologic and clinical variables were analysed. RESULTS: Cool (p = 0.0090) and warm detection thresholds (p = 0.0229) of the tongue were higher in BMS patients than controls. The stimulation threshold for SON BR was higher in patients than in controls (p = 0.0056). The latencies of R2 component were longer in BMS patients than in controls (p = 0.0005) at the SON distribution. Habituation of SON BR did not differ between the groups. The heat pain thresholds were highest (p = 0.0312) in homozygous patients with 957TT, who also reported most interference (p = 0.0352) and greatest suffering (p = 0.0341). Genotype 957CC associated with sleep disturbances (p = 0.0254). CONCLUSIONS: Burning mouth syndrome patients showed thermal hypoesthesia within LN distribution compatible with small fibre neuropathy. The DRD2 957C>T genotype influences perception and experience of BMS pain. SIGNIFICANCE: The results confirm earlier findings of neuropathic pain in BMS. The DRD2 957 C>T genotype influences perception and experience of clinical pain in BMS.

World Workshop on Oral Medicine VII: Burning mouth syndrome: A systematic review of disease definitions and diagnostic criteria utilized in randomized clinical trials.

OBJECTIVE: To conduct a systematic review analyzing disease definitions and diagnostic criteria used in randomized controlled trials (RCTs) involving burning mouth syndrome (BMS). METHODS: A systematic search conducted in PubMed, Web of Science, PsycINFO, Cochrane Database/Cochrane Central, and Google Scholar that included RCTs on BMS published between 1994 and 2017 was performed. RESULTS: Considerable variability in BMS disease definitions and diagnostic criteria used created substantial heterogeneity in the selection of participants and weakened the rigor of the 36 RCTs identified. The analyzed RCTs routinely under-reported the methods used to rule in or out study participants and the number of individuals excluded from BMS RCTs. CONCLUSIONS: Our findings indicate that a large proportion of participants enrolled in these studies may have had an underlying condition that could have explained their BMS symptoms. Thus, outcomes of therapeutic interventions from these BMS RCTs should be interpreted with caution due to heterogeneous disease definitions and diagnostic criteria. In order to improve the quality of clinical trials, future research should focus on establishing consensus for a single definition of BMS that includes specific inclusion and exclusion criteria that should be used to select study participants for clinical trials.

Painful temporomandibular disorders (TMD) and comorbidities in primary care: associations with pain-related disability.

Objective: We studied whether primary care temporomandibular disorder (TMD) patients reporting different levels of pain-related disability differ in terms of comorbid pains, general health conditions and quality of life.Material and methods: Consecutive TMD pain patients (n = 399) seeking treatment in primary care completed a questionnaire on comorbid pains and their interference and the Finnish version of the RAND-36-item quality of life questionnaire. Medical diagnoses confirmed by doctors were recorded. The patients were classified according to the Graded Chronic Pain Scale (GCPS) of the Research Diagnostic Criteria for TMD (RDC/TMD). The patients were classified: no disability group (0 disability points), low disability group (1-2 disability points) and high disability group (3-6 disability points).Results: Compared to patients in the no-disability group, patients in the high- and low-disability groups reported more comorbid pain conditions (p < .001), and experienced these as more intense and interfering more with daily life (p < .05). Patients in the high-disability group reported more general health-related medical diagnoses than patients in the no-disability group (p < .05). Furthermore, patients with low or high pain-related disability indicated poorer quality of life in all RAND-36 subscales than those with no disability (p < .05).Conclusions: The findings suggest that GCPS-related disability scoring can be used as a simple screening instrument to identify TMD patients with different degrees of health burdens.

Validation of diagnostic methods for traumatic sensory neuropathy and neuropathic pain.

INTRODUCTION: We evaluated diagnostic value of sensory tests during recovery from iatrogenic sensory neuropathy using intraoperatively verified nerve injury with subjective symptoms as gold standard. METHODS: Inferior alveolar nerves were monitored neurophysiologically throughout mandibular osteotomy in 19 patients. Sensory disturbance was registered and sensation tested using clinical and quantitative sensory (QST) and neurophysiologic tests postoperatively at 1, 3, 6, and 12 months. Sensitivity, specificity, and predictive values were calculated for all tests. RESULTS: The sensitivity of clinical tests was at best 37%, with 100% specificity, but they lost diagnostic value at chronic stages. Best diagnostic accuracy (highest combination of sensitivity and specificity) at different time points was achieved by combining neurophysiologic and thermal QST or tactile and thermal QST. The single most accurate test was sensory neurography. CONCLUSIONS: Neurography or combinations of neurophysiologic and quantitative tests enables most reliable early and late diagnosis. Clinical sensory examination is inadequate for accurate diagnosis. Muscle Nerve 59:342-347, 2019.

Validation of EQ-5D and 15D in the assessment of health-related quality of life in chronic pain.

Chronic pain has a significant impact on quality of life. Measurement of health-related quality of life (HRQoL) is essential in the assessment of pain management outcomes, but different instruments have produced varying results. We assessed the validity of 2 HRQoL instruments, EuroQol 5 dimensions questionnaire (EQ-5D) and 15-dimensional health-related quality of life measure (15D), in patients with challenging chronic pain. Three hundred ninety-one chronic noncancer pain patients referred to tertiary pain clinics completed EQ-5D, 15D, and a broad set of questionnaires mapping socioeconomic factors, self-rated health, pain intensity and interference, depression, pain acceptance, pain-related anxiety, and sleep. The 2 HRQoL instruments were compared with each other, and head-to-head comparisons were made with self-rated health and the symptom-specific questionnaires. 15D and EQ-5D showed moderate agreement (ρ = 0.66), but there were also considerable differences between the instruments. 15D correlated better with self-rated health than EQ-5D (ρ = -0.62 vs -0.45, P < 0.001). The EQ-5D appeared less sensitive than 15D especially in those patients with chronic pain who had a better health status. The principal component constructed from measures of pain intensity and interference, anxiety, pain acceptance, depression, and sleep had higher standardized beta coefficients with 15D than with EQ-5D (P = 0.038). The principal component explained more variance in the 15D (R = 0.65) than in the EQ-5D (R = 0.43). The study identified differences in the pain-related variables between the EQ-5D and the 15D. In patients with chronic pain, both instruments are valid, but 15D appears somewhat more sensitive than EQ-5D.

The analgesic effect of therapeutic rTMS is not mediated or predicted by comorbid psychiatric or sleep disorders.

BACKGROUND: Mechanisms underlying alleviation of neuropathic pain by repetitive transcranial magnetic stimulation (rTMS) of primary motor cortex (M1) and right secondary somatosensory cortex (S2) are only partly known. Patients with chronic neuropathic pain often have comorbidities like depression and sleep problems. Through functional connectivity, rTMS of M1 and S2 may activate dorsolateral prefrontal cortex, the target for treating depression with rTMS. Thus, the analgesic effect of rTMS could be mediated indirectly via improvement of psychiatric comorbidities or sleep. We examined whether rTMS has an independent analgesic effect or whether its clinical benefits depend on effects on mood or sleep. We also evaluated if comorbid psychiatric or sleep disorders predict the treatment outcome. METHODS: Sixteen patients with chronic drug-resistant neuropathic orofacial pain participated in this randomized controlled crossover rTMS study. Patients' psychiatric history was evaluated by a specialist in psychiatry. Intensity and interference of pain, mood, and the quality of sleep and life were evaluated at baseline and after 2 active (primary somatosensory cortex [S1]/M1 and S2) and placebo rTMS treatments. A logistic regression analysis was done to investigate predictors of treatment outcome. RESULTS: The analgesic effect of the right S2 stimulation was not associated with improvement of psychiatric conditions or sleep, whereas S1/M1 stimulation improved sleep without significant analgesic effect (P = 0.013-0.046 in sleep scores). Psychiatric and sleep disorders were more common in patients than in the general population (P = 0.000-0.001 in sleep scores), but these comorbidities did not predict the rTMS treatment outcome. CONCLUSION: We conclude that rTMS to the right S2 does not exert its beneficial analgesic effects in chronic neuropathic orofacial pain via indirect improvement of comorbid psychiatric or sleep disorders.

Interventions for treating burning mouth syndrome.

BACKGROUND: Burning mouth syndrome (BMS) is a term used for oral mucosal pain (burning pain or discomfort in the tongue, lips or entire oral cavity) without identifiable cause. General population prevalence varies from 0.1% to 3.9%. Many BMS patients indicate anxiety, depression, personality disorders and impaired quality of life (QoL). This review updates the previous versions published in 2000 and 2005. OBJECTIVES: To determine the effectiveness and safety of any intervention versus placebo for symptom relief and changes in QoL, taste, and feeling of dryness in people with BMS. SEARCH METHODS: Cochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (to 31 December 2015), the Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 11) in the Cochrane Library (searched 31 December 2015), MEDLINE Ovid (1946 to 31 December 2015), and Embase Ovid (1980 to 31 December 2015). We searched ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform for ongoing trials. We placed no restrictions on the language or date of publication when searching the electronic databases SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing any treatment against placebo in people with BMS. The primary outcomes were symptom relief (pain/burning) and change in QoL. Secondary outcomes included change in taste, feeling of dryness, and adverse effects. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Outcome data were analysed as short-term (up to three months) or long-term (three to six months). MAIN RESULTS: We included 23 RCTs (1121 analysed participants; 83% female). Interventions were categorised as: antidepressants and antipsychotics, anticonvulsants, benzodiazepines, cholinergics, dietary supplements, electromagnetic radiation, physical barriers, psychological therapies, and topical treatments.Only one RCT was assessed at low risk of bias overall, four RCTs' risk of bias was unclear, and 18 studies were at high risk of bias. Overall quality of the evidence for effectiveness was very low for all interventions and all outcomes.Twenty-one RCTs assessed short-term symptom relief. There is very low-quality evidence of benefit from electromagnetic radiation (one RCT, 58 participants), topical benzodiazepines (two RCTs, 111 participants), physical barriers (one RCT, 50 participants), and anticonvulsants (one RCT, 100 participants). We found insufficient/contradictory evidence regarding the effectiveness of antidepressants, cholinergics, systemic benzodiazepines, dietary supplements or topical treatments. No RCT assessing psychological therapies evaluated short-term symptom relief.Four studies assessed long-term symptom relief. There is very low-quality evidence of a benefit from psychological therapies (one RCT, 30 participants), capsaicin oral rinse (topical treatment) (one RCT, 18 participants), and topical benzodiazepines (one RCT, 66 participants). We found no evidence of a difference for dietary supplements or lactoperoxidase oral rinse. No studies assessing antidepressants, anticonvulsants, cholinergics, electromagnetic radiation or physical barriers evaluated long-term symptom relief.Short-term change in QoL was assessed by seven studies (none long-term).The quality of evidence was very low. A benefit was found for electromagnetic radiation (one RCT, 58 participants), however findings were inconclusive for antidepressants, benzodiazepines, dietary supplements and physical barriers.Secondary outcomes (change in taste and feeling of dryness) were only assessed short-term, and the findings for both were also inconclusive.With regard to adverse effects, there is very low-quality evidence that antidepressants increase dizziness and drowsiness (one RCT, 37 participants), and that alpha lipoic acid increased headache (two RCTs, 118 participants) and gastrointestinal complaints (3 RCTs, 138 participants). We found insufficient/contradictory evidence regarding adverse events for anticonvulsants or benzodiazepines. Adverse events were poorly reported or unreported for cholinergics, electromagnetic radiation, and psychological therapies. No adverse events occurred from physical barriers or topical therapy use. AUTHORS' CONCLUSIONS: Given BMS' potentially disabling nature, the need to identify effective modes of treatment for sufferers is vital. Due to the limited number of clinical trials at low risk of bias, there is insufficient evidence to support or refute the use of any interventions in managing BMS. Further clinical trials, with improved methodology and standardised outcome sets are required in order to establish which treatments are effective. Future studies are encouraged to assess the role of treatments used in other neuropathic pain conditions and psychological therapies in the treatment of BMS.

Assessment of Pain Drawings and Self-Reported Comorbid Pains as Part of the Biopsychosocial Profiling of Temporomandibular Disorder Pain Patients.

AIMS: To assess drawings of pain sites and self-reported comorbid pains as a part of the biopsychosocial profiling of tertiary care referral patients with temporomandibular disorder (TMD) pain. METHODS: A total of 135 consecutive patients referred to tertiary care for TMD pain participated. Patients drew all the sites where they had pain on whole-body pain drawings. Other assessments included self-reported comorbid pains in the head and body regions, the Finnish Research Diagnostic Criteria for TMD (RDC/TMD_FIN Axis II), and additional biopsychosocial and treatment-related variables. Patients were grouped into pain drawing profiles (localized, regional, and widespread) and the associations between these profiles and the biopsychosocial variables were statistically evaluated using Bonferroni adjusted P values and with logistic regression using SAS 9.3. RESULTS: A total of 21% of the patients reported localized TMD pain, 20% reported regional pain (headaches and neckaches), and the majority, 59%, reported widespread pain (local/regional and multiple bodily pain sites). Patients with widespread pain profiles formed a heterogenous group in which 28.2% reported severe and 30.8% reported moderate pain-related disability. The widespread pain patients reported significantly higher levels of depression and somatization, lower levels of general health, more sleep dysfunction, decreased ability to control pain, and greater health care needs compared to patients with localized pain (P < .05). Patients with regional pain profiles reported moderate scores on psychosocial functioning compared to the patients with localized or widespread pain. CONCLUSION: The majority of tertiary care referral patients with TMD pain reported comorbid pains. Pain drawings were found a useful adjunctive tool for screening and as a part of comprehensive biopsychosocial assessment and treatment planning for patients with TMD pain.

Explanatory Models of Illness and Treatment Goals in Temporomandibular Disorder Pain Patients Reporting Different Levels of Pain-Related Disability.

AIMS: To explore whether temporomandibular disorder (TMD) pain patients reporting different levels of pain-related disability differ in terms of illness explanations and treatment expectations. METHODS: Consecutive TMD pain patients (n = 399; mean ± SD age, 40.5 ± 12.7 years; 83% women) seeking treatment in primary care completed the Explanatory Model Scale (EMS). Patients were asked to indicate their expectations regarding the treatment. Each patient's pain-related disability level was determined using the Graded Chronic Pain Scale, with scores indicating no (0 disability points), low (1-2 disability points), or high (3-6 disability points) disability. Differences between EMS factor scores were evaluated using the Mann-Whitney U test. Differences between study groups were analyzed using logistic regression. RESULTS: High-disability patients considered physical and stress factors as more important in causing and in aggravating pain and as targets of treatment compared with patients with no disability (P = .0196 and P = .0251, respectively). The great majority of patients indicated they would like to receive information, decrease pain, and increase jaw function, with no significant subtype differences noted. Compared with no-disability patients, low-disability and high-disability patients were more likely to expect increased ability to perform daily functions (P < .0001 in both comparisons), increased work ability (P < .0001 in both comparisons), and better stress management skills (P = .0014 and P = .0001, respectively). CONCLUSION: Illness explanations and goals for treatment differ in patients reporting different levels of TMD pain-related disability.

Right secondary somatosensory cortex-a promising novel target for the treatment of drug-resistant neuropathic orofacial pain with repetitive transcranial magnetic stimulation.

High-frequency repetitive transcranial magnetic stimulation (rTMS) of the motor cortex has analgesic effect; however, the efficacy of other cortical targets and the mode of action remain unclear. We examined the effects of rTMS in neuropathic orofacial pain, and compared 2 cortical targets against placebo. Furthermore, as dopaminergic mechanisms modulate pain responses, we assessed the influence of the functional DRD2 gene polymorphism (957C>T) and the catechol-O-methyltransferase (COMT) Val158Met polymorphism on the analgesic effect of rTMS. Sixteen patients with chronic drug-resistant neuropathic orofacial pain participated in this randomized, placebo-controlled, crossover study. Navigated high-frequency rTMS was given to the sensorimotor (S1/M1) and the right secondary somatosensory (S2) cortices. All subjects were genotyped for the DRD2 957C>T and COMT Val158Met polymorphisms. Pain, mood, and quality of life were monitored throughout the study. The numerical rating scale pain scores were significantly lower after the S2 stimulation than after the S1/M1 (P = 0.0071) or the sham (P = 0.0187) stimulations. The Brief Pain Inventory scores were also lower 3 to 5 days after the S2 stimulation than those at pretreatment baseline (P = 0.0127 for the intensity of pain and P = 0.0074 for the interference of pain) or after the S1/M1 (P = 0.001 and P = 0.0001) and sham (P = 0.0491 and P = 0.0359) stimulations. No correlations were found between the genetic polymorphisms and the analgesic effect in the present small clinical sample. The right S2 cortex is a promising new target for the treatment of neuropathic orofacial pain with high-frequency rTMS.

Subtyping patients with temporomandibular disorders in a primary health care setting on the basis of the research diagnostic criteria for temporomandibular disorders axis II pain-related disability: a step toward tailored treatment planning?

AIMS: To use the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) Axis II and additional pain-related and psychosocial variables to identify subtypes of TMD patients in a primary health care setting based on pain-related disability. METHODS: Consecutive TMD pain patients (n = 399) seeking treatment in a primary care setting completed a multidimensional pain questionnaire. Subtyping was based on the Graded Chronic Pain Scale (GCPS), and the patients were divided into a no-disability group (0 disability points), lowdisability group (1-2 disability points), and high-disability group (3-6 disability points). Psychosocial variables included RDC/TMD Axis II variables, anxiety, tension and stress, worry, catastrophizing, coping ability, general health, and other pain problems. Subtype differences were analyzed with t test, Wilcoxon rank-sum test, ANOVA, or Kruskal-Wallis test. A further analysis with multivariable logistic model was applied. All P values from pairwise comparisons were Bonferroni adjusted. RESULTS: Most (61%) of the patients belonged to the no-disability group, 27% to the low-disability group, and 12% to the high-disability group. When subtypes were compared, patients in the no-disability group appeared psychosocially well-functioning, with fewer symptoms related to psychosocial distress, better ability to control pain, and fewer jaw functional limitations and other pain problems. Patients in the high-disability group reported the highest levels of symptoms of depression and somatization, sleep dysfunction, worry, and catastrophizing thoughts. The low-disability patients formed an intermediate group between the no-disability and high-disability groups. CONCLUSION: The results suggest that GCPS-related disability scoring can be used as a simple screening instrument in primary care settings to identify individuals with different, clinically relevant psychosocial subtypes.

Variation in the dopamine D2 receptor gene plays a key role in human pain and its modulation by transcranial magnetic stimulation.

We tested whether variation of the dopamine D2 receptor (DRD2) gene contributes to individual differences in thermal pain sensitivity and analgesic efficacy of repetitive transcranial magnetic stimulation (rTMS) in healthy subjects (n=29) or susceptibility to neuropathic pain in patients with neurophysiologically confirmed diagnosis (n=16). Thermal sensitivity of healthy subjects was assessed before and after navigated rTMS provided to the S1/M1 cortex. All subjects were genotyped for the DRD2 gene 957C>T and catechol-O-methyltransferase (COMT) protein Val158Met polymorphisms. In healthy subjects, 957C>T influenced both innocuous and noxious thermal detection thresholds that were lowest in 957TT homozygotes (P values from .0277 to .0462). rTMS to S1 cortex had analgesic effect only in 957TT homozygote genotype (P=.0086). In patients, prevalence of 957TT homozygote genotype was higher than in a healthy Finnish population (50% vs 27%; P=.0191). Patients with 957TT genotype reported more severe pain than patients with other genotypes (P=.0351). COMT Val158Met polymorphism was not independently associated with the studied variables. Genetic regulation of DRD2 function by 957C>T polymorphism thus seems to influence thermal and pain sensitivity, its modulation by rTMS, and susceptibility to neuropathic pain. This indicates a central role for the dopamine system and DRD2 in pain and analgesia. This may have clinical implications regarding individualized selection of patients for rTMS treatment and assessment of risks for neuropathic pain.