The Computerized General Neuropsychological INPH Test revealed improvement in idiopathic normal pressure hydrocephalus after shunt surgery.

OBJECTIVE: The Computerized General Neuropsychological INPH Test (CoGNIT) provides the clinician and the researcher with standardized and accessible cognitive assessments in patients with idiopathic normal pressure hydrocephalus (INPH). CoGNIT includes tests of memory, executive functions, attention, manual dexterity, and psychomotor speed. Investigations of the validity and reliability of CoGNIT have been published previously. The aim of this study was to evaluate CoGNIT's sensitivity to cognitive change after shunt surgery in patients with INPH. METHODS: Forty-one patients with INPH (median Mini-Mental State Examination score 26) were given CoGNIT preoperatively and at a postoperative follow-up 4 months after shunt surgery. Scores were compared to those of 44 healthy elderly control volunteers. CoGNIT was administered by either a nurse or an occupational therapist. RESULTS: Improvement after shunt surgery was seen in all cognitive domains: memory (10-word list test, p < 0.01); executive functions (Stroop incongruent color and word test, p < 0.01); attention (2-choice reaction test, p < 0.01); psychomotor speed (Stroop congruent color and word test, p < 0.01); and manual dexterity (4-finger tapping, p < 0.01). No improvement was seen in the Mini-Mental State Examination score. Preoperative INPH test scores were significantly impaired compared to healthy control subjects (p < 0.001 for all tests). CONCLUSIONS: In this study the feasibility for CoGNIT to detect a preoperative impairment and postoperative improvement in INPH was demonstrated. CoGNIT has the potential to become a valuable tool in clinical and research work.Clinical trial registration no.: NCT01618500 (clinicaltrials.gov).

Vascular risk factors in INPH: A prospective case-control study (the INPH-CRasH study).

OBJECTIVE: To assess the complete vascular risk factor (VRF) profile of idiopathic normal pressure hydrocephalus (INPH) using a large sample of representative patients with INPH and population-based controls to determine the extent to which vascular disease influences INPH pathophysiology. METHODS: All patients with INPH who underwent shunting in Sweden in 2008-2010 were compared to age- and sex-matched population-based controls. Inclusion criteria were age 60-85 years and no dementia. The 10 most important VRFs and cerebrovascular and peripheral vascular disease were prospectively assessed using blood samples, clinical examinations, and standardized questionnaires. Assessed VRFs were hypertension, hyperlipidemia, diabetes, obesity, psychosocial factors, smoking habits, diet, alcohol intake, cardiac disease, and physical activity. RESULTS: In total, 176 patients with INPH and 368 controls participated. Multivariable logistic regression analysis indicated that hyperlipidemia (odds ratio [OR] 2.380; 95% confidence interval [CI] 1.434-3.950), diabetes (OR 2.169; 95% CI 1.195-3.938), obesity (OR 5.428; 95% CI 2.502-11.772), and psychosocial factors (OR 5.343; 95% CI 3.219-8.868) were independently associated with INPH. Hypertension, physical inactivity, and cerebrovascular and peripheral vascular disease were also overrepresented in INPH. Moderate alcohol intake and physical activity were overrepresented among the controls. The population-attributable risk percentage was 24%. CONCLUSIONS: Our findings confirm that patients with INPH have more VRFs and lack the protective factors present in the general population. Almost 25% of cases of INPH may be explained by VRFs. This suggests that INPH may be a subtype of vascular dementia. Targeted interventions against modifiable VRFs are likely to have beneficial effects on INPH.

Incidence and outcome of surgery for adult hydrocephalus patients in Sweden.

OBJECT: To present population-based and age related incidence of surgery and clinical outcome for adult patients operated for hydrocephalus, registered in the Swedish Hydrocephalus Quality Registry (SHQR). METHODS: All patients registered in SHQR during 2004-2011 were included. Data on age, gender, type of hydrocephalus and type of surgery were extracted as well as three months outcome for patients with idiopathic normal pressure hydrocephalus (iNPH). RESULTS: The material consisted of 2360 patients, 1229 men and 1131 women, age 63.8 ± 14.4 years (mean ± standard deviation (SD)). The mean total incidence of surgery was 5.1 ± 0.9 surgeries/100,000/year; 4.7 ± 0.9 shunt surgeries and 0.4 ± 0.1 endoscopic third ventriculostomies. For iNPH, secondary communicating hydrocephalus and obstructive hydrocephalus, the incidence of surgery was 2.2 ± 0.8, 1.9 ± 0.3 and 0.8 ± 0.1/100,000/year, respectively. During 2004-2011, the incidence of surgery increased in total (p = .044), especially in age groups 70-79 years and ≥80 years (p = .012 and p = .031). After surgery, 253 of 652 iNPH patients (38.8%) improved at least one step on the modified Rankin scale (mRS). Number needed to treat was 3.0 for improving one patient from unfavourable (mRS 3-5) to favourable (mRS 0-2). The mean score of a modified iNPH scale increased from 54 ± 23 preoperatively to 63 ± 25 postoperatively (p < .0001, n = 704), and 58% improved. No significant regional differences in incidence, surgical techniques or outcome were found. CONCLUSIONS: Incidence of hydrocephalus surgery increased significantly during 2004-2011, specifically in elderly patients. Surgical treatment of iNPH markedly improved functional independence, but the improvement rate was low compared to recent single- and multicentre studies. Thus, the potential for surgical improvement is likely lower than generally reported when treating patients as part of everyday clinical care.

Preoperative and postoperative 1H-MR spectroscopy changes in frontal deep white matter and the thalamus in idiopathic normal pressure hydrocephalus.

BACKGROUND: In a previous study we found significantly decreased N-acetyl aspartate (NAA) and total N-acetyl (tNA) groups in the thalamus of patients with idiopathic normal pressure hydrocephalus (iNPH) compared with healthy individuals (HI). No significant difference between the groups could be found in the frontal deep white matter (FDWM). OBJECTIVE: The primary aim of this study was to investigate if these metabolites in the thalamus were normalised after shunt surgery. The secondary aim was to investigate postoperative metabolic changes in FDWM. SUBJECTS AND METHODS: Fourteen patients with iNPH, mean age 74 years, and 15 HI, also mean age 74 years, were examined. Assessment of a motor score (MOSs) was performed before and after shunt surgery. Absolute quantitative (1)H-MR spectroscopy (1.5 T, volumes of interest 2.5-3 ml) was performed on the patients in the FDWM and in the thalamus, before and 3 months after shunt surgery, and also once on the HI. The following metabolites were analysed: tNA, NAA, total creatine, total choline (tCho), myo-inositol (mIns), glutamate and lactate concentrations. MRI volumetric calculations of the lateral ventricles were also performed. RESULTS: At 3 months postoperatively, we found no significant changes of tNA or NAA in the thalamus. In contrast, in the FDWM, there was a significant increase of tCho (p=0.01) and a borderline significant decrease of mIns (p=0.06). 12/14 patients were shunt responders (motor function). Median reduction of the lateral ventricle was 16%. A weak correlation between MOS and ventricular reduction was seen. CONCLUSIONS: Normalisation of thalamic tNA and NAA could not be detected postoperatively. The increased tCho and decreased mIns in the FDWM postoperatively might relate to clinical improvement.

5% lidocaine medicated plaster versus pregabalin in post-herpetic neuralgia and diabetic polyneuropathy: an open-label, non-inferiority two-stage RCT study.

OBJECTIVE: To compare efficacy and safety of 5% lidocaine medicated plaster with pregabalin in patients with post-herpetic neuralgia (PHN) or painful diabetic polyneuropathy (DPN). STUDY DESIGN AND METHODS: This was a two-stage adaptive, randomized, open-label, multicentre, non-inferiority study. Data are reported from the initial 4-week comparative phase, in which adults with PHN or painful DPN received either topical 5% lidocaine medicated plaster applied to the most painful skin area or twice-daily pregabalin capsules titrated to effect according to the Summary of Product Characteristics. The primary endpoint was response rate at 4 weeks, defined as reduction averaged over the last three days from baseline of > or = 2 points or an absolute value of < or = 4 points on the 11-point Numerical Rating Scale (NRS-3). Secondary endpoints included 30% and 50% reductions in NRS-3 scores; change in allodynia severity rating; quality of life (QoL) parameters EQ-5D, CGIC, and PGIC; patient satisfaction with treatment; and evaluation of safety (laboratory parameters, vital signs, physical examinations, adverse events [AEs], drug-related AEs [DRAEs], and withdrawal due to AEs). RESULTS: Ninety-six patients with PHN and 204 with painful DPN were analysed (full analysis set, FAS). Overall, 66.4% of patients treated with the 5% lidocaine medicated plaster and 61.5% receiving pregabalin were considered responders (corresponding numbers for the per protocol set, PPS: 65.3% vs. 62.0%). In PHN more patients responded to 5% lidocaine medicated plaster treatment than to pregabalin (PPS: 62.2% vs. 46.5%), while response was comparable for patients with painful DPN (PPS: 66.7% vs 69.1%). 30% and 50% reductions in NRS-3 scores were greater with 5% lidocaine medicated plaster than with pregabalin. Both treatments reduced allodynia severity. 5% lidocaine medicated plaster showed greater improvements in QoL based on EQ-5D in both PHN and DPN. PGIC and CGIC scores indicated greater improvement for 5% lidocaine medicated plaster treated patients with PHN. Improvements were comparable between treatments in painful DPN. Fewer patients administering 5% lidocaine medicated plaster experienced AEs (safety set, SAF: 18.7% vs. 46.4%), DRAEs (5.8% vs. 41.2%) and related discontinuations compared to patients taking pregabalin. CONCLUSION: 5% lidocaine medicated plaster showed better efficacy compared with pregabalin in patients with PHN. Within DPN, efficacy was comparable for both treatments. 5% lidocaine medicated plaster showed a favourable efficacy/safety profile with greater improvements in patient satisfaction and QoL compared with pregabalin for both indications, supporting its first line position in the treatment of localized neuropathic pain.

Efficacy and safety of combination therapy with 5% lidocaine medicated plaster and pregabalin in post-herpetic neuralgia and diabetic polyneuropathy.

OBJECTIVE: Neuropathic pain is often difficult to treat due to a complex pathophysiology. This study evaluated the efficacy, tolerability and safety of combination therapy with 5% lidocaine medicated plaster and pregabalin for neuropathic pain in patients with post-herpetic neuralgia (PHN) or painful diabetic polyneuropathy (DPN). METHODS: Patients completing 4-week monotherapy with 5% lidocaine medicated plaster or pregabalin were enrolled in an 8-week combination phase. Patients with adequate response to monotherapy (recalled average pain intensity of 4 or less on 11-point numeric rating scale in the previous 3 days [NRS-3 score]) continued their previous therapy, whereas those with insufficient response received combination therapy. Efficacy endpoints included change in NRS-3 from combination phase baseline, Patient and Clinical Global Impression of Change (PGIC/CGIC), and patient's satisfaction with treatment. Safety evaluation included adverse events (AEs), drug-related AEs (DRAEs), and withdrawal due to AEs. CLINICAL TRIAL REGISTRATION: EudraCT No. 2006-003132-29. RESULTS: Of 229 patients in the per-protocol set (PPS: 68 PHN and 161 DPN), 71 received 5% lidocaine medicated plaster monotherapy, 57 had pregabalin added to 5% lidocaine medicated plaster, 57 pregabalin monotherapy and 44 received 5% lidocaine medicated plaster in addition to continued pregabalin treatment. There were no meaningful differences in demographic data between the treatment groups. Patients continuing on monotherapy demonstrated additional decreases in NRS-3 scores. Patients receiving combination therapy achieved clinically relevant reduction in NRS-3 values in addition to improvement achieved during the 4 weeks of monotherapy. Improvement was similar between the two combination therapy groups. Considerable improvements in patients' treatment satisfaction were reported. Incidences of AEs were in line with previous reports for the two treatments and combination therapy was generally well tolerated. CONCLUSIONS: In patients with PHN and painful DPN failing to respond to monotherapy, combination therapy with 5% lidocaine medicated plaster and pregabalin provides additional clinically relevant pain relief and is safe and well-tolerated.

Efficacy and safety of 5% lidocaine (lignocaine) medicated plaster in comparison with pregabalin in patients with postherpetic neuralgia and diabetic polyneuropathy: interim analysis from an open-label, two-stage adaptive, randomized, controlled trial.

BACKGROUND AND OBJECTIVE: Postherpetic neuralgia (PHN) and diabetic polyneuropathy (DPN) are two common causes of peripheral neuropathic pain. Typical localized symptoms can include burning sensations or intermittent shooting or stabbing pains with or without allodynia. Evidence-based treatment guidelines recommend the 5% lidocaine (lignocaine) medicated plaster or pregabalin as first-line therapy for relief of peripheral neuropathic pain. This study aimed to compare 5% lidocaine medicated plaster treatment with pregabalin in patients with PHN and patients with DPN. METHODS: The study was a two-stage, adaptive, randomized, controlled, open-label, multicentre trial that incorporated a drug wash-out phase of up to 2 weeks prior to the start of the comparative phase. At the end of the enrollment phase, patients who fulfilled the eligibility criteria were randomized to either 5% lidocaine medicated plaster or pregabalin treatment and entered the 4-week comparative phase. The interim analysis represents the first stage of the two-stage adaptive trial design and was planned to include data from the comparative phase for the first 150 randomized patients of the 300 total planned for the trial. Patients aged > or = 18 years with PHN or DPN were recruited from 53 investigational centres in 14 European countries. For this interim analysis, 55 patients with PHN and 91 with DPN (full-analysis set [FAS]), randomly assigned to the treatment groups, were available for analysis. Topical 5% lidocaine medicated plaster treatment was administered by patients to the area of most painful skin. A maximum of three or four plasters were applied for up to 12 hours within each 24-hour period in patients with PHN or DPN, respectively. Pregabalin capsules were administered orally, twice daily. The dose was titrated to effect: all patients received 150 mg/day in the first week and 300 mg/day in the second week of treatment. After 1 week at 300 mg/day, the dose of pregabalin was further increased to 600 mg/day in patients with high pain intensity scores. The pre-planned primary study endpoint was the rate of treatment responders, defined as completing patients experiencing a reduction from baseline of > or = 2 points or an absolute value of < or = 4 points on the 11-item numerical rating scale of recalled average pain intensity over the last 3 days (NRS-3), after 4 weeks of treatment. Secondary endpoints included > or = 30% and > or = 50% reductions in NRS-3 scores, changes in neuropathic pain symptom inventory (NPSI) scores and allodynia severity ratings. Overall, 65.3% of patients treated with the 5% lidocaine medicated plaster and 62.0% receiving pregabalin responded to treatment with respect to the primary endpoint. A higher proportion of PHN patients responded to plaster treatment compared with pregabalin (63.0% vs 37.5%), whereas in the larger DPN group treatments were comparable. Both treatments improved NPSI scores and reduced allodynia severity. Patients administering lidocaine plaster experienced fewer drug-related adverse events (3.9% vs 39.2%) and there were substantially fewer discontinuations due to drug-related adverse events (1.3% vs 20.3%). CONCLUSION: After 4 weeks, 5% lidocaine medicated plaster treatment was associated with similar levels of analgesia in patients with PHN or DPN but substantially fewer frequent adverse events than pregabalin.

Somatosensory abnormalities in atypical odontalgia: A case-control study.

Somatosensory function in patients with persistent idiopathic types of orofacial pain like atypical odontalgia (AO) is not well described. This study tested the hypothesis that AO patients have significantly more somatosensory abnormalities than age- and sex-matched controls. Forty-six AO patients and 35 controls participated. Inclusion criteria for AO were pain in a region where a tooth had been endodontically or surgically treated, persistent pain >6 months, and lack of clinical and radiological findings. The examination included qualitative tests and a battery of intraoral quantitative sensory testing (QST). Most AO patients (85%) had qualitative somatosensory abnormality compared with few controls (14%). The most common qualitative abnormalities in AO patients were found with pin-prick 67.4%, cold 47.8%, and touch 46.5% compared with 11.4%, 8.6%, and 2.9%, respectively, in the control group (P<0.001). Between-group differences were seen for many intraoral QST: mechanical detection threshold, mechanical pain threshold (pinprick), dynamic mechanical allodynia (brush), dynamic mechanical allodynia (vibration), wind-up ratio, and pressure pain threshold (P<0.01). In the trigeminal area, between-group differences in thermal thresholds were nonsignificant while differences in cold detection at the thenar eminence were significant. Individual somatosensory profiles revealed complex patterns with hyper- and hyposensitivity to intraoral QST. Between-group differences in pressure pain thresholds (P<0.02) were observed at the thenar eminence. In conclusion, significant abnormalities in intraoral somatosensory function were observed in AO, which may reflect peripheral and central sensitization of trigeminal pathways. More generalized sensitization of the nociceptive system may also be part of AO pathophysiology.

Comparison of clinical findings and psychosocial factors in patients with atypical odontalgia and temporomandibular disorders.

AIMS: To systematically compare clinical findings and psychosocial factors between patients suffering from atypical odontalgia (AO) and an age- and gender-matched group of patients with temporomandibular disorders (TMD). METHODS: Forty-six AO patients (7 men and 39 women; mean age, 56 years) were compared with 41 TMD patients (8 men and 33 women; mean age, 58 years). RESULTS: Mean pain intensity at the time of inclusion in the study was similar between the groups (TMD: 5.3 +/- 0.4, AO: 5.0 +/- 0.3), but pain duration was longer in AO patients (AO: 7.7 +/- 1.1 years, TMD: 4.5 +/- 0.1 years). Eighty-three percent of the AO patients and 15% of TMD patients reported pain onset in relation to dental/surgical procedures. Episodic tension-type headache (TTH) occurred equally in both groups (TMD: 46%, AO: 46%), but TMD patients more frequently experienced chronic TTH (TMD: 35%, AO: 18%), myofascial TMD (TMD: 93%, AO: 50%), and temporomandibular joint disorders (TMD: 66%, AO: 2%). Overall, TMD patients had lower pressure pain thresholds and poorer jaw function than AO patients. Mean depression and somatization scores were moderate to severe in both groups, and widespread pain was most common in TMD patients. CONCLUSION: AO and TMD share some characteristics but differ significantly in report of dental trauma, jaw function, pain duration, and pain site.

Experienced dilemmas of everyday life in chronic neuropathic pain patients--results from a critical incident study.

Neuropathic pain is a disabling chronic condition with limited therapeutic options. Few studies have addressed patient's experience and strategies. The aim of this study was to explore dilemmas experienced in order to improve care and rehabilitation. An interview study with 39 patients suffering from neuropathic pain of different origin was performed. We used the critical incident technique to collect data. Questions on occasions when patients had been hindered by or reminded of their neuropathic pain were included, and the self-perceived consequences and management of such occasions. The interviews were transcribed verbatim and analysed qualitatively. A broad range of experiences categorised into dilemmas, disturbances, consequences and managements from most parts of everyday life was identified. The dilemmas were 'housework', 'sitting', 'physical activity', 'personal hygiene', 'sleeping difficulties', 'hypersensitivity to external stimuli', 'social relationships', 'transportation' and 'leisure time'. Disturbances were 'failures', 'inabilities' and 'restrictions'. Consequences were 'increased pain', 'psychological reactions' and 'physical symptoms'. The majority of the patients used activity-oriented strategies to manage their pain such as alternative ways of performing the task, a cognitive approach or simply ignoring the pain. This is one of the first studies presenting detailed data on everyday dilemmas, disturbances and consequences of patients with chronic neuropathic pain. Such information is important in clinical settings to improve care and rehabilitation.

Clinical findings and psychosocial factors in patients with atypical odontalgia: a case-control study.

AIM: To provide a systematic description of clinical findings and psychosocial factors in patients suffering from atypical odontalgia (AO). METHODS: Forty-six consecutive AO patients (7 men and 39 women; mean age, 56 years; range, 31 to 81 years) were compared with 35 control subjects (11 men and 24 women; mean age, 59 years; range, 31 to 79 years). RESULTS: The pain of the AO patients was characterized by persistent, moderate pain intensity (mean, 5.6 +/- 1.9) with long pain duration (mean, 7.7 +/- 7.8 years). Eighty-three percent reported that onset of pain occurred in conjunction with dental treatment. No significant difference was found between the groups in number of remaining teeth or number of root fillings. Temporomandibular disorder (TMD) pain (P < .001), tension-type headache (P < .002), and widespread pain (P < .001) were significantly more common among AO patients than controls. Significantly higher scores for somatization (P < .01) and depression (P < .01) and limitations in jaw function (P < .001) were found for the AO group compared with the control group. Significant differences between groups were found in 4 general health domains: role-physical (P < .001), bodily pain (P < .001), vitality (P < .004), and social functioning (P < .001). CONCLUSION: A majority of the AO patients reported persistent, moderately intense intraoral pain that in most cases had an onset in conjunction with dental treatment. AO patients had more comorbid pain conditions and higher scores for depression and somatization. Significant limitation in jaw function and significantly lower scores on quality of life measures were found for AO patients compared with controls.

Effect of local anesthesia on atypical odontalgia--a randomized controlled trial.

The aim of the study was to evaluate the analgesic effect of lidocaine in a double-blind, controlled multi-center study on patients with atypical odontalgia (AO)--a possible orofacial neuropathic pain condition. Thirty-five consecutive AO patients (range 31-81 years) with a mean pain duration of 7.2 years (range 1-30 years) were recruited from four different orofacial pain clinics in Sweden. In a randomized cross-over design, 1.5 ml local anesthesia (20mg/ml lidocaine and 12.5 microg/ml adrenaline) or 1.5 ml saline (9 mg/ml NaCl solution) (placebo) was injected to block the painful area. The VAS pain scores showed an overall effect of time (ANOVA: P<0.001) and treatment (ANOVA: P=0.018) with a significant interaction between the factors (ANOVA: P<0.001). Overall, VAS pain relief was significantly greater at 15-120 min following the lidocaine injections compared to the placebo injections (Tukey: P<0.05). All patients demonstrated significant disturbances in somatosensory function on the painful side compared to the non-painful side as revealed by quantitative sensory tests, however, only one significant inverse correlation was found between percentage pain relief and the magnitude of brush-evoked allodynia (Spearman: P<0.01). In conclusion, AO patients experienced significant, but not complete, pain relief from administration of local anesthetics compared with placebo. The findings indicate that the spontaneous pain in AO patients only to some extent is dependent on peripheral afferent inputs and that sensitization of higher order neurons may be involved in the pathophysiology of AO.

Blink reflexes in patients with atypical odontalgia.

AIMS: To use the human blink reflex (BR) to explore possible neuropathic pain mechanisms in patients with atypical odontalgia (AO). METHODS: In 13 AO patients, the BR was elicited using a concentric electrode and recorded bilaterally with surface electromyographic (EMG) electrodes on both orbicularis oculi muscles. Electrical stimuli were applied to the skin above branches of the V1, V2, and V3 nerves and to the V branch contralateral to the painful branch. Sensory and pain thresholds were determined. The BR examination of the painful V branch was repeated during a capsaicin pain-provocation test. The data were analyzed with nonparametric statistics. RESULTS: The BR responses (R2 and R3) evoked by stimulation of V3 were significantly smaller than the BR responses evoked by stimulation of V1 and V2 (P < .004). There were no differences in BR (R2 or R3) between the painful and nonpainful sides (P > .569), and the BR (R2 and R3) was not significantly modulated by experimental pain (P > .080). The sensory thresholds were significantly lower on the painful side compared to the nonpainful side (P = .014). The pain thresholds were not different between sides (P > .910). CONCLUSION: No major differences between the V nociceptive pathways on the right and left sides were found in a relatively small group of AO patients. Future studies that compare BRs in AO patients and healthy volunteers are needed to provide further knowledge on the pain mechanisms in AO.

Pharmacologic interventions in the treatment of temporomandibular disorders, atypical facial pain, and burning mouth syndrome. A qualitative systematic review.

AIMS: To carry out a systematic review of the literature in order to assess the pain-relieving effect and safety of pharmacologic interventions in the treatment of chronic temporomandibular disorders (TMD), including rheumatoid arthritis (RA), as well as atypical facial pain (AFP), and burning mouth syndrome (BMS). METHODS: Study selection was based on randomized clinical trials (RCTs). Inclusion criteria included studies on adult patients (> or = 18 years) with TMD, RA of the temporomandibular joint (TMJ), AFP, or BMS and a pain duration of > 3 months. Data sources included Medline, Cochrane Library, Embase, and Psych Litt. RESULTS: Eleven studies with a total of 368 patients met the inclusion criteria. Four trials were on TMD patients, 2 on AFP, 1 on BMS, 1 on RA of the TMJ, and 3 on mixed groups of patients with TMD and AFP. Of the latter, amitriptyline was effective in 1 study and benzodiazepine in 2 studies; the effect in 1 of the benzodiazepine studies was improved when ibuprofen was also given. One study showed that intra-articular injection with glucocorticoid relieved the pain of RA of the TMJ. In 1 study, a combination of paracetamol, codeine, and doxylamine was effective in reducing TMD pain. No effective pharmacologic treatment was found for BMS. Only minor adverse effects were reported in the studies. CONCLUSION: The common use of analgesics in TMD, AFP, and BMS is not supported by scientific evidence. More large RCTs are needed to determine which pharmacologic interventions are effective in TMD, AFP, and BMS.