Change In Average Pain Intensity Research Articles

Low-dose naltrexone for the treatment of fibromyalgia: protocol for a double-blind, randomized, placebo-controlled trial

BackgroundLow-dose naltrexone (LDN) is used widely as an off-label treatment for pain despite limited evidence for its effectiveness. A few small trials with a high risk of bias have investigated the effect of LDN on pain associated with fibromyalgia in women, but larger and more methodologically robust studies are needed. The primary aim of this randomized controlled trial is to investigate if 12 weeks of LDN treatment is superior to placebo in reducing the average pain intensity during the last 7 days in women with fibromyalgia.MethodsA single-center, permuted block randomized, double-blind, placebo-controlled, parallel-group trial will be performed in Denmark. Randomization comprises 100 women aged 18–64 years diagnosed with fibromyalgia who will be treated with either LDN or placebo for 12 weeks including a 4-week titration phase. The primary outcome is change in average pain intensity (during the last 7 days) from baseline to 12 weeks. Secondary outcomes are other fibromyalgia-related symptoms, i.e., tenderness, fatigue, sleep disturbance, stiffness, memory problems, depression, anxiety and measures of global assessment, physical function, impact of fibromyalgia, pain distribution, and health-related quality of life. Intention-to-treat analysis will be performed, and the number of responders with a more than 15%, 30%, and 50% improvement of pain after 12 weeks will be calculated for the LDN and placebo groups. Exploratory outcomes include measures of pain sensitivity, muscle performance, and biomarkers.DiscussionThis study will contribute with high-level evidence on the efficacy of low-dose naltrexone for the treatment of pain in women with fibromyalgia. Secondary outcomes include both disease-specific and generic components investigating whether LDN influences other symptoms than pain. Explorative outcomes are included to provide greater insight into the mechanism of action of LDN and possibly a better understanding of the underlying pathology in fibromyalgia.Trial registrationEudraCT 2019-000702-30. Registered on 12 July 2019. ClinicalTrials.gov NCT04270877. Registered on 17 February 2020

An 8-Week Self-Administered At-Home Behavioral Skills-Based Virtual Reality Program for Chronic Low Back Pain: Double-Blind, Randomized, Placebo-Controlled Trial Conducted During COVID-19.

BackgroundChronic low back pain is the most prevalent chronic pain condition worldwide and access to behavioral pain treatment is limited. Virtual reality (VR) is an immersive technology that may provide effective behavioral therapeutics for chronic pain.ObjectiveWe aimed to conduct a double-blind, parallel-arm, single-cohort, remote, randomized placebo-controlled trial for a self-administered behavioral skills-based VR program in community-based individuals with self-reported chronic low back pain during the COVID-19 pandemic.MethodsA national online convenience sample of individuals with self-reported nonmalignant low back pain with duration of 6 months or more and with average pain intensity of 4 or more/10 was enrolled and randomized 1:1 to 1 of 2 daily (56-day) VR programs: (1) EaseVRx (immersive pain relief skills VR program); or (2) Sham VR (2D nature content delivered in a VR headset). Objective device use data and self-reported data were collected. The primary outcomes were the between-group effect of EaseVRx versus Sham VR across time points, and the between–within interaction effect representing the change in average pain intensity and pain-related interference with activity, stress, mood, and sleep over time (baseline to end-of-treatment at day 56). Secondary outcomes were global impression of change and change in physical function, sleep disturbance, pain self-efficacy, pain catastrophizing, pain acceptance, pain medication use, and user satisfaction. Analytic methods included intention-to-treat and a mixed-model framework.ResultsThe study sample was 179 adults (female: 76.5%, 137/179; Caucasian: 90.5%, 162/179; at least some college education: 91.1%, 163/179; mean age: 51.5 years [SD 13.1]; average pain intensity: 5/10 [SD 1.2]; back pain duration ≥5 years: 67%, 120/179). No group differences were found for any baseline variable or treatment engagement. User satisfaction ratings were higher for EaseVRx versus Sham VR (P<.001). For the between-groups factor, EaseVRx was superior to Sham VR for all primary outcomes (highest P value=.009), and between-groups Cohen d effect sizes ranged from 0.40 to 0.49, indicating superiority was moderately clinically meaningful. For EaseVRx, large pre–post effect sizes ranged from 1.17 to 1.3 and met moderate to substantial clinical importance for reduced pain intensity and pain-related interference with activity, mood, and stress. Between-group comparisons for Physical Function and Sleep Disturbance showed superiority for the EaseVRx group versus the Sham VR group (P=.022 and .013, respectively). Pain catastrophizing, pain self-efficacy, pain acceptance, prescription opioid use (morphine milligram equivalent) did not reach statistical significance for either group. Use of over-the-counter analgesic use was reduced for EaseVRx (P<.01) but not for Sham VR.ConclusionsEaseVRx had high user satisfaction and superior and clinically meaningful symptom reduction for average pain intensity and pain-related interference with activity, mood, and stress compared to sham VR. Additional research is needed to determine durability of treatment effects and to characterize mechanisms of treatment effects. Home-based VR may expand access to effective and on-demand nonpharmacologic treatment for chronic low back pain.Trial RegistrationClinicalTrials.gov NCT04415177; https://clinicaltrials.gov/ct2/show/NCT04415177International Registered Report Identifier (IRRID)RR2-10.2196/25291

Transcutaneous electrical nerve stimulation for advanced cancer pain inpatients in specialist palliative care\u2014a blinded, randomized, sham-controlled pilot cross-over trial

PurposeTranscutaneous electrical nerve stimulation (TENS) is a treatment option for cancer pain, but the evidence is inconclusive. We aimed to evaluate the efficacy and safety of TENS.MethodsA blinded, randomized, sham-controlled pilot cross-over trial (NCT02655289) was conducted on an inpatient specialist palliative care ward. We included adult inpatients with cancer pain ≥ 3 on an 11-point numerical rating scale (NRS). Intensity-modulated high TENS (IMT) was compared with placebo TENS (PBT). Patients used both modes according to their preferred application scheme during 24 h with a 24-h washout phase. The primary outcome was change in average pain intensity on the NRS during the preceding 24 h. Responders were patients with at least a “slight improvement.”ResultsOf 632 patients screened, 25 were randomized (sequence IMT-PBT = 13 and PBT-IMT = 12). Finally, 11 patients in IMT-PBT and 9 in PBT-IMT completed the study (N = 20). The primary outcome did not differ between groups (IMT minus PBT: − 0.2, 95% confidence interval − 0.9 to 0.6). However, responder rates were higher in IMT (17/20 [85%] vs. 10/20 [50%], p = 0.0428). Two patients experienced an uncomfortable feeling caused by the current, one after IMT and one after PBT. Seven patients (35%) desired a TENS prescription. Women and patients with incident pain were most likely to benefit from TENS.ConclusionTENS was safe, but IMT was unlikely to offer more analgesic effects than PBT. Even though many patients desired a TENS prescription, 50% still reported at least “slight pain relief” from PBT. Differences for gender and incident pain aspects demand future trials.

Treatment of at-level spinal cord injury pain with botulinum toxin A.

Study designRandomized, double-blinded, placebo-controlled, cross-over study.ObjectiveTo explore whether botulinum toxin A (BoNTA) could be effective for treating at-level spinal cord injury (SCI) pain.SettingOutpatient SCI clinic, New York, USA.MethodsParticipants were randomized to receive subcutaneous injections of either placebo or BoNTA with follow-up (office visit, telephone, or e-mail) at 2, 4, 8, and 12 weeks to assess the magnitude of pain relief post injection. Crossover of participants was then performed. Those who received placebo received BoNTA, and vice versa, with follow-up at 2, 4, 8, and 12 weeks.ResultsEight participants completed at least one of the two crossover study arms. Four completed both arms. The median age of the eight participants was 45 years (range 32–61 years) and 75% were male. All had traumatic, T1-L3 level, complete SCI. Although our data did not meet statistical significance, we noted a higher proportion of participants reporting a marked change in average pain intensity from baseline to 8 and 12 weeks post-BoNTA vs. post-placebo (33% vs. 0%). At 2 and 4 weeks post-BoNTA, almost all participants reported some degree of reduced pain, while the same was not seen post-placebo (83% vs. 0%).ConclusionThe subcutaneous injection of BoNTA may be a feasible approach for the control of at-level SCI pain and is worthy of further study.SponsorshipThe onabotulinumtoxinA (BOTOX) used in this study was provided by Allergan (Irvine, CA).

Effectiveness of 2 Osteopathic Treatment Approaches on Pain, Pressure-Pain Threshold, and Disease Severity in Patients with Fibromyalgia: A Randomized Controlled Trial

Objective: To assess the effectiveness of osteopathic intervention (OI) and general osteopathic treatment (GOT) in individuals with fibromyalgia syndrome (FMS). Methods: The trial was designed as a randomized controlled trial with 2 osteopathic interventions and 1 untreated control group. The patients in the two osteopathic groups received 10 osteopathic treatments (OI or GOT) within a time period of 12 weeks. The control group did not receive any osteopathic treatment. The primary outcome was the average pain intensity (API) assessed by visual analog scale (VAS). Secondary outcomes were the pressure-pain threshold rated by means of a tender point score, and disease severity, assessed by the Fibromyalgia Impact Questionnaire (FIQ). Results: 50 patients were randomized. The primary outcome parameter API decreased from 7.2 to 4.7 in the OI group, from 6.3 to 4.3 in the GOT group, and increased slightly in the control group from 6.2 to 6.6. There were significant differences for the change in API between the OI group and the control group (VAS: 2.9, 95% confidence interval (CI) = 1.12-4.52), and between the GOT group and the control group (VAS: 2.4, 95% CI = 0.65-4.11), but no significant differences between the OI group and the GOT group. There were no significant differences for the secondary outcome parameters between the groups. Conclusion: A series of osteopathic treatments might be beneficial for patients suffering from FMS.

Acupuncture for the treatment of phantom limb syndrome in lower limb amputees: a randomised controlled feasibility study.

BackgroundPost amputation, the complication of phantom limb pain (PLP) is prevalent and difficult to manage. This study aimed to determine whether it was feasible and acceptable to undertake a definitive multicentred randomised controlled trial assessing the effectiveness of acupuncture for treating lower limb amputees with PLP.MethodsA mixed-methods embedded design, including a randomised controlled trial and semistructured interviews, was undertaken. A total of 15 participants with PLP were randomly assigned to receive either eight pragmatic Traditional Chinese Medicine acupuncture treatments and usual care or usual care alone over 4 weeks. Outcome measures were completed at baseline, weekly throughout the study and at 1 month post completion of the study and included: a numerical pain-rating scale, the Short-Form McGill Pain Questionnaire 2, the EQ-5D-5 L, the Hospital Anxiety and Depression Scale, the Perceived Stress Scale 10-item, the Insomnia Severity Index, and the Patient Global Impression of Change. Post completion of the trial, participants in the acupuncture group were interviewed about their experience. Feasibility-specific data were also collected.ResultsOf 24 amputees meeting the study inclusion criteria, 15 agreed to participate (recruitment rate 62.50 %). Qualitatively, acupuncture was perceived to be beneficial and effective. Quantitatively, acupuncture demonstrated clinically meaningful change in average pain intensity (raw change = 2.69) and worst pain intensity (raw change = 4.00). Feasibility-specific data identified that before undertaking a definitive trial, recruitment, practitioner adherence to the acupuncture protocol, completion of outcome measures at 1 month follow-up and blinding should be addressed. Appropriate outcome measures were identified for use in a definitive trial. Data were generated for future sample size calculations (effect size 0.64). Allowing for a 20 % dropout rate, a sample size of 85 participants per group would be needed in a future definitive trial.ConclusionsA future definitive trial may be possible if the areas identified in this study are addressed. As acupuncture may be effective at treating PLP, and as this feasibility study suggests that a definitive trial may be possible, a multicentred trial with adequate sample size and blinding is now needed.Trial registrationClinicalTrials.gov Identifier: NCT02126436, registered on 4 September 2014.Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-016-1639-z) contains supplementary material, which is available to authorized users.

Single-Entity Hydrocodone Extended-Release Capsules in Opioid-Tolerant Subjects with Moderate-to-Severe Chronic Low Back Pain: A Randomized Double-Blind, Placebo-Controlled Study

A single-agent, extended-release formulation of hydrocodone (HC) has been developed for treatment of chronic moderate-to-severe pain. This study was designed to examine the safety and efficacy of HC extended release in opioid-experienced adults with moderate-to-severe chronic low back pain (CLBP). This multicenter, enriched enrollment, randomized withdrawal study comprised an open-label conversion/titration phase (≤6 weeks) followed by placebo-controlled, double-blind treatment (12 weeks). During the conversion/titration phase, subjects (N = 510) converted from their current opioid and were titrated to a stabilized dose of HC extended release (20-100 mg every 12 hours). During treatment, subjects (N = 151 per group) received HC extended release or placebo; rescue medication was permitted. The primary efficacy end point was mean change in average pain intensity from baseline to day 85. Response rates (30% pain improvement) and satisfaction (Subject Global Assessment of Medication) were assessed. Demographic and baseline characteristics were similar between groups. Mean ± SD change in average pain intensity score from baseline to day 85 was significantly lower in the HC extended-release treatment group vs placebo (0.48 ± 1.56 vs 0.96 ± 1.55; P = 0.008). Significantly more responders were in the treatment group (68% vs 31%; P < 0.001). Mean Subject Global Assessment of Medication scores increased significantly (0.8 ± 1.3 vs 0.0 ± 1.4; P < 0.0001), indicating greater satisfaction with HC extended release. The adverse event profile was consistent with other opioids. Extended-release HC is well tolerated and effective, without acetaminophen-associated risks of liver toxicity, for treatment of CLBP.

Heated lidocaine/tetracaine patch for treatment of patellar tendinopathy pain

IntroductionThe pain of patellar tendinopathy (PT) may be mediated by neuronal glutamate and sodium channels. Lidocaine and tetracaine block both of these channels. This study tested the self-heated lidocaine-tetracaine patch (HLT patch) in patients with PT confirmed by physical examination to determine if the HLT patch might relieve pain and improve function.MethodsThirteen patients with PT pain of ≥14 days’ duration and baseline average pain scores ≥4 (on a 0–10 scale) enrolled in and completed this prospective, single-center pilot study. Patients applied one HLT patch to the affected knee twice daily for 2–4 hours for a total of 14 days. Change in average pain intensity and interference (Victorian Institute of Sport Assessment [VISA]) scores from baseline to day 14 were assessed. No statistical inference testing was performed.ResultsAverage pain scores declined from 5.5 ± 1.3 (mean ± standard deviation) at baseline to 3.8 ± 2.5 on day 14. Similarly, VISA scores improved from 45.2 ± 14.4 at baseline to 54.3 ± 24.5 on day 14. A clinically important reduction in pain score (≥30%) was demonstrated by 54% of patients.ConclusionThe results of this pilot study suggest that topical treatment that targets neuronal sodium and glutamate channels may be useful in the treatment of PT.

Efficacy and tolerability of tapentadol extended release (ER) in patients with chronic, painful diabetic peripheral neuropathy (DPN): results of a phase 3, randomized-withdrawal, placebo-controlled study

This Phase 3, randomized-withdrawal, placebo-controlled study (NCT01041859) evaluated the efficacy and tolerability of tapentadol ER for the management of neuropathic pain associated with DPN. Adult patients with moderate to severe, painful DPN with symptoms for ≥6 months and ≥3-month history of analgesic use for painful DPN were titrated to an optimal dose (balancing efficacy and tolerability) of tapentadol ER (100-250 mg bid) during a 3-week open-label period. At the end of the titration period, patients with ≥1-point reduction in pain intensity from the beginning to end of titration were randomized (1:1) to receive placebo or their pre-determined optimal dose of tapentadol ER for 12 weeks (double-blind, fixed dose, maintenance phase). The primary efficacy endpoint was mean change in average pain intensity (recorded twice daily [average pain during previous 12 hours]; 11-point NRS) from the start to Week 12 (LOCF) of the double-blind maintenance phase. Treatment-emergent adverse events (TEAEs) were recorded. A total of 358 patients completed the open-label titration period; 318 patients (placebo, n=152; tapentadol ER, n=166) were randomized and received ≥1 dose of study medication. At the start versus Week 12 of double-blind maintenance, respectively, mean (SD) pain intensity was: tapentadol ER, 3.70 (1.78) versus 4.01 (2.23); placebo, 3.35 (2.17) versus 4.83 (2.60). Mean (SD) change in average pain intensity from the start to Week 12 of the double-blind maintenance phase was: tapentadol ER, 0.28 (2.042); placebo, 1.30 (2.428) (least-squares mean difference for tapentadol ER vs placebo, –0.95 [95% CI, –1.415 to –0.493]; P <0.001 favoring tapentadol ER). TEAEs (≥10%) reported in the tapentadol ER group during double-blind maintenance were nausea (21.1%) and vomiting (12.7%). Tapentadol ER (100-250 mg bid) was effective and well tolerated for the management of moderate to severe, neuropathic pain associated with DPN in adults. Supported by Janssen Research & Development, L.L.C., and Grünenthal GmbH.

A Spicamycin Derivative (KRN5500) Provides Neuropathic Pain Relief in Patients With Advanced Cancer: A Placebo-Controlled, Proof-of-Concept Trial

ContextNeuropathic pain in patients with cancer can be difficult to treat effectively. ObjectivesThe purpose of the study was to determine safety and efficacy of KRN5500, a novel, spicamycin-derived, nonopioid analgesic agent, in patients with advanced cancer and neuropathic pain of any etiology. MethodsThe study was a Phase 2a, multicenter, double-blind, placebo-controlled, dose escalation clinical trial. Patients with refractory neuropathic pain and advanced cancer were randomly assigned 2:1 to receive a maximum of eight single escalating doses of KRN5500 or placebo, ranging from 0.6 to 2.2mg/m2. The primary objective was safety and tolerability. The secondary objective was efficacy, measured by change in average pain intensity on a 0–10 numeric rating scale administered one week after the patient’s final dose. ResultsNineteen patients received treatment (KRN5500 n=12; placebo n=7). The most frequently reported adverse events were gastrointestinal symptoms, which were more frequent and severe with KRN5500 than placebo; two (17%) KRN5500 patients discontinued the study because of nausea and vomiting. At study endpoint, KRN5500 exhibited a significant median decrease in pain intensity from baseline of 24% compared with 0% for placebo (P=0.03). The median for largest weekly reduction in target pain intensity was 29.5% for KRN5500 and 0% for placebo patients (P=0.02). ConclusionThis proof-of-concept study for KRN5500 in patients with advanced cancer and any type of neuropathic pain found gastrointestinal adverse events to be the predominant safety concern. The results also provided the first indication of clinical and statistical efficacy in reducing pain intensity.

Safety and efficacy of tapentadol ER in patients with painful diabetic peripheral neuropathy: results of a randomized-withdrawal, placebo-controlled trial

Objective:Painful diabetic peripheral neuropathy (DPN) may not be adequately managed with available therapeutic options. This phase III, randomized-withdrawal, placebo-controlled trial evaluated the safety and efficacy of tapentadol extended release (ER) for relieving painful DPN.Research design and methods:Patients (n = 588) with at least a 3-month history of opioid and/or non-opioid analgesic use for DPN, dissatisfaction with current treatment, and an average pain intensity score of at least 5 on an 11-point numerical rating scale (NRS; 0 = ‘no pain,’ 10 = ‘pain as bad as you can imagine’) were titrated to an optimal dose of tapentadol ER (100–250 mg bid) during a 3-week open-label phase. Subsequently, patients (n = 395) with at least a 1-point reduction in pain intensity were randomized 1:1 to receive placebo or the optimal fixed dose of tapentadol ER determined during the open-label phase for a 12-week double-blind phase.Clinical trial registration: NCT00455520.Main outcome measures:The primary efficacy outcome was the change in average pain intensity from randomization, determined by twice-daily NRS measurements. Safety was assessed throughout the study.Results:The least-squares mean difference between groups in the change in average pain intensity from the start of double-blind treatment to week 12 was −1.3 (95% confidence interval, −1.70 to −0.92; p < 0.001, tapentadol ER vs. placebo). A total of 60.5% (356/588) of patients reported at least a 30% improvement in pain intensity from the start to the end of the open-label titration phase; of the patients who were randomized to tapentadol ER, 53.6% (105/196) reported at least a 30% improvement from pre-titration to week 12 of the double-blind phase. The most common treatment-emergent adverse events that occurred during double-blind treatment with tapentadol ER included nausea, anxiety, diarrhea, and dizziness. Potential limitations of this study are related to the enriched enrollment randomized-withdrawal trial design, which may result in a more homogeneous patient population during double-blind treatment and may present a risk of unblinding because of changes in side effects from the open-label to the double-blind phase.Conclusions:Compared with placebo, tapentadol ER 100–250 mg bid provided a statistically significant difference in the maintenance of a clinically important improvement in pain and was well-tolerated by patients with painful DPN.

Poster 269: Titration of Oxymorphone Extended Release in Opioid-Experienced Patients With Chronic Low Back Pain Due to a Herniated Disk or Degenerative Disk Disease

Objective: Evaluate the effectiveness and tolerability of a program of gradual titration with oxymorphone extended-release (oxymorphone ER) in patients with chronic low back pain (CLBP) due to a herniated disk(s) (HD) or degenerative disk disease (DDD). Design: Subgroup analysis of a randomized controlled trial. Setting: Multidisciplinary pain centers. Participants: Opioid-experienced adults with moderate to severe CLBP despite opioid therapy equivalent to greater than or equal to 60mg/d of oral morphine. Interventions: Patients were converted from their previous opioid and gradually titrated for less than or equal to 1 month to a dose of oxymorphone ER (q12 h) that reduced pain to less than or equal to 40mm on a 100-mm visual analog scale with less than or equal to 2 daily doses of 5mg oxymorphone immediate-release rescue medication. Main Outcome Measures: Patient disposition, change in average pain intensity, and adverse events (AEs) in HD and DDD subgroups during titration to a stable oxymorphone ER dose. Results: Titration was successfully completed by the majority of patients in the DDD (53 out of 97; 54.6%) and HD (29 out of 48; 60.4%) groups. Discontinuations due to AEs accounted for 24.7% (DDD) and 10.4% (HD) of patients. Discontinuations due to lack of efficacy were 4% in each group. The most frequent AEs were nausea (19.6%−18.8%), constipation (14.4%−10.4%), and headache (14.4%−16.7%) in the DDD and HD groups; most were mild or moderate (86−87%). Mean stabilized doses of oxymorphone ER were 89.9mg/d and 105mg/d in DDD and HD patients, respectively. Successfully titrated patients experienced a decrease in pain from a median of 71mm at screening (both groups) to 26.0 and 27.5mm following titration in the DDD and HD groups, respectively. Conclusions: The majority of patients with CLBP due to DDD or HD were titrated to an effective, generally well-tolerated oxymorphone ER dose. Differences in back pain etiology did not preclude successful outcomes, as both groups experienced large, clinically significant reductions in pain.

Morphine versus Mexiletine for Treatment of Postamputation Pain

Stump and phantom pains are debilitating sequelae of amputations that are often resistant to treatment. The efficacy of pharmacologic therapies, including opioids and sodium channel blockers, for postamputation pain is uncertain. The authors conducted a double-blind, randomized, placebo-controlled, crossover study in adult patients with postamputation pain of 6 months or longer and greater than 3 on a 0-10 numeric pain rating scale. Each of the three treatment periods (morphine, mexiletine, or placebo) included a 1-week drug-free interval followed by 4-week titration, 2-week maintenance, and 2-week drug-taper phases. The primary outcome measure was change in average pain intensity from the drug-free baseline to the last week of maintenance. Sixty amputees were enrolled; data were analyzed from 56 subjects for one drug period, 45 subjects for two drug periods, and 35 subjects who completed all three drug periods. The mean morphine and mexiletine dosages were 112 and 933 mg, respectively. Morphine treatment provided lower pain scores compared with placebo and mexiletine (P = 0.0003). The mean percent pain relief during treatment with placebo, mexiletine, and morphine was 19, 30, and 53%, respectively (P < 0.0001, morphine vs. placebo and mexiletine). The numbers needed to treat to obtain 50% and 33% decreases in pain intensity with morphine were 5.6 and 4.5, respectively. Treatment with morphine was associated with a higher rate of side effects. Therapy with morphine, but not mexiletine, resulted in a decrease in intensity of postamputation pain but was associated with a higher rate of side effects and no improvement in self-reported levels of overall functional activity and pain-related interference in daily activities.

Five-year outcomes in TMD: relationship of changes in pain to changes in physical and psychological variables

Factors influencing natural history and clinical course of pain in temporomandibular disorders (TMD) are largely unknown. Physical, psychological and behavioral data from a population-based epidemiologic study of TMD were examined in 234 cases of persons reporting TMD pain. The cases were assigned to one of five pain pattern groups based on changes in average TMD pain from baseline to 5-year follow-up: (i) remitted (49% of the sample), (ii) high-improvement (14%), (iii) low-improvement (9%), (iv) same (13%), and (v) worse (16%). For each pain change group, an ANOVA-derived pattern analysis was performed to assess whether the pattern of change in each of seven physical and three psychological variables was congruent or dissimilar to the pattern of change in average pain intensity. For none of the physical or psychological variables was the change over time completely congruent with the changes in pain. Changes in ambient average TMD pain were most closely related to those clinical variables whose assessment is influenced by pain or other self-reported symptoms (e.g., number of muscle sites painful to examiner palpation), while the amount of pain change was less closely related to changes in clinical variables, such as joint sounds, where assessment is not dependent on subjective report. The three psychological variables, anxiety, depression, and somatization, displayed similar change patterns, but these patterns were distinctly different from those of the physical variables in that the remitted pain group was at the population mean at baseline for these psychological variables and remained there; significant improvement in psychological status was observed only in the pain group showing high improvement. The other three pain change groups exhibited elevated psychological distress scores at both baseline and 5 years. These results indicate that although the relationships among the course of pain, of physical variables, and of psychological variables are complicated, the 5-year outcome in pain is largely independent of readily discernible changes in clinical signs.