Management of chronic pain secondary to temporomandibular disorders: a systematic review and network meta-analysis of randomised trials

Meta-epidemiological studies found little to no effect of blinding on treatment results among randomised trials, including a review of oral health trials.

“based on meta-epidemiological studies [22][23][24][25] that found little to no effect of blinding on treatment results among randomised trials (including a review of oral health trials 26 )”

• cites [22] sourcePartly supported

  The Discussion reports no evidence of an average difference in estimated treatment effects between blinded and non-blinded randomised trials. Its “Other studies” section says an oral-health trial study found no evidence of an effect from blinding outcome assessors, but some evidence of a moderate effect from blinding patients. Thus the unqualified “little to no effect” summary misses an important exception for oral-health trials. (LLM, conf=0.84)

  Experimental — accuracy not yet measured
• cites [23] sourcePartly supported

  The Results (page unavailable) report negligible or little evidence of bias from lack of blinding for several analyses, including outcomes analysed together. But the same section reports exaggerated treatment effects when subjective outcomes were assessed without blinding, so the unqualified claim of little to no effect overstates the review. The oral-health review is attached to a separate citation in the citing sentence. (LLM, conf=0.88)

  Experimental — accuracy not yet measured
• cites [24] sourceNot checked — no full text of the source

There have been nine prior network meta-analyses of interventions for chronic temporomandibular disorder pain.

“There have been nine prior network meta-analyses (NMAs) of interventions for chronic TMD pain.[6][7][8][9][10][11][12][13][14]”

• cites [6] sourceNot checked — no full text of the source
• cites [7] sourceNot checked — no full text of the source
• cites [8] sourceSupported

In total, 148 RCTs involving 7867 patients and evaluating 59 interventions reported effects on pain.

“In total, 148 RCTs involving 7867 patients and evaluating 59 interventions reported effects on pain (fig 2).”

The updated literature search in January 2023 identified 13 additional eligible trials that enrolled a total of 875 patients.

“Our updated literature search in January 2023, identified 13 additional eligible trials that enrolled a total of 875 patients”

In the 31 direct comparisons with two or more studies available for conventional pairwise meta-analysis, there was substantial heterogeneity (I2 >70%) for 11 comparisons.

“In the 31 direct comparisons with two or more studies available for conventional pairwise metaanalysis, there was substantial heterogeneity (I 2 >70%) for 11 comparisons”

78 studies (51%) concealed allocation.

“78 (51%) concealed allocation”

There was no evidence of global or loop-specific incoherence in the pain network.

“We found no evidence of global or loop-specific incoherence (supplement table 9).”

Compared with placebo, effects on pain for eight interventions were supported by moderate to high certainty evidence.

“Compared with placebo, effects on pain for eight interventions were supported by moderate to high certainty evidence.”

118 studies (77%) adequately generated their randomisation sequence.

“118 studies (77%) adequately generated their randomisation sequence”

Most trials (133/153, 87%) were at risk for bias for at least one domain.

“Most trials (133/153, 87%) were at risk for bias for at least one domain”

Four interventions reported in three studies (arthrocentesis, arthrocentesis with steroid injection, arthrocentesis with hyaluronic acid injection, and discectomy) were disconnected from the network.

“four interventions reported in three studies (that is, arthrocentesis, arthrocentesis with steroid injection, arthrocentesis with hyaluronic acid injection, and discectomy) were disconnected from the network”

Most trials did not report effects on adverse events.

“Most trials did not report effects on adverse events”

There was no evidence of global or loop-specific incoherence in the physical functioning network.

“We found no evidence of global or loop-specific incoherence (supplement table 12).”

The certainty in effects for all other interventions was low or very low.

“The certainty in effects for all other interventions was low or very low (fig 3).”

Supervised jaw exercise with stretching probably improves physical functioning compared with placebo in patients with chronic temporomandibular disorders, with a risk difference for achieving the minimally important difference of 43% (95% CI 33 to 51) and moderate certainty evidence.

“supervised jaw exercise with stretching (RD for achieving the minimally important difference of 5 points on the 100 point short form-36 physical component summary score 43% (95% CI 33 to 51))”

• AssumptionThe authors state this as an assumption: The standard deviations of outcome measures are the same in both the treatment and control groups.
• AssumptionThe authors state this as an assumption: Change scores in both the treatment and control groups are normally distributed.

In subgroup analysis, trials at high risk of bias were associated with larger treatment effects for pain relief for removeable occlusal splint versus placebo.

“1) removeable occlusal splint versus placebo, which found trials at high risk of bias were associated with larger treatment effects for pain relief”

Therapist-assisted jaw mobilisation had a modelled risk difference for achieving the minimally important difference in pain relief of 36% (95% CI 31 to 40).

“therapist-assisted jaw mobilisation (RD 36% (31 to 40))”

The certainty in effects on adverse events for all 19 interventions was low or very low.

“The certainty in effects on adverse events for all 19 interventions was low or very low (fig 3).”

The network for physical functioning included 33 RCTs with 1910 patients that evaluated 26 interventions.

“our network included 33 RCTs with 1910 patients that evaluated 26 interventions (fig 4).”

None of the prior network meta-analyses assessed all available interventions across all temporomandibular disorder subtypes.

“None of them, however, assessed all available interventions across all TMD subtypes (supplement table 21).”

The certainty of evidence for the 19 interventions reporting on adverse events was low to very low.

“the certainty of evidence for the 19 interventions reporting on adverse events was low to very low.”

The review was unable to construct networks for mental functioning, role functioning, social functioning, or sleep quality due to the small numbers of trials reporting these outcomes.

“We were unable to construct networks for mental functioning, role functioning, social functioning, or sleep quality due to the small numbers of trials reporting these outcomes.”

Supervised jaw exercise with mobilisation probably improves physical functioning compared with placebo in patients with chronic temporomandibular disorders, with a risk difference for achieving the minimally important difference of 36% (95% CI 19 to 51) and moderate certainty evidence.

“supervised jaw exercise with mobilisation (RD 36% (19 to 51))”

• AssumptionThe authors state this as an assumption: The standard deviations of outcome measures are the same in both the treatment and control groups.
• AssumptionThe authors state this as an assumption: Change scores in both the treatment and control groups are normally distributed.

Supervised jaw exercise with stretching and manual trigger point therapy had a modelled risk difference for achieving the minimally important difference in pain relief of 23% (95% CI 11 to 31).

“supervised jaw exercise with stretching and manual trigger point therapy (RD 23% (11 to 31))”

Acupuncture probably improves physical functioning compared with placebo in patients with chronic temporomandibular disorders, with a risk difference for achieving the minimally important difference of 42% (95% CI 33 to 50) and moderate certainty evidence.

“acupuncture (RD 42% (33 to 50))”

• AssumptionThe authors state this as an assumption: The standard deviations of outcome measures are the same in both the treatment and control groups.
• AssumptionThe authors state this as an assumption: Change scores in both the treatment and control groups are normally distributed.

Supervised postural exercise had a modelled risk difference for achieving the minimally important difference in pain relief of 26% (95% CI 14 to 34).

“supervised postural exercise (RD 26% (14 to 34))”

Thirty six trials with 2009 patients, evaluating 30 interventions, reported treatment effects on physical functioning.

“Thirty six trials with 2009 patients, evaluating 30 interventions, reported treatment effects on physical functioning”

The certainty in effects for physical functioning among interventions other than supervised jaw exercise with stretching, manipulation, acupuncture, and supervised jaw exercise with mobilisation was low or very low.

“The certainty in effects for physical functioning among other interventions was low or very low (fig 3).”

• Also stated in: § Discussion · plain

  “The certainty in effects, among other interventions, was low or very low.”

Adverse events were reported in only 31 studies involving 1987 patients with chronic temporomandibular disorders.

“Adverse events were only reported in 31 studies involving 1987 patients with chronic TMD (fig 5, supplement table 13).”

Supervised jaw exercise with stretching had a modelled risk difference for achieving the minimally important difference in pain relief of 26% (95% CI 20 to 31).

“supervised jaw exercise with stretching (RD 26% (20 to 31))”

Manipulation probably improves physical functioning compared with placebo in patients with chronic temporomandibular disorders, with a risk difference for achieving the minimally important difference of 43% (95% CI 25 to 56) and moderate certainty evidence.

“manipulation (RD 43% (25 to 56))”

• AssumptionThe authors state this as an assumption: The standard deviations of outcome measures are the same in both the treatment and control groups.
• AssumptionThe authors state this as an assumption: Change scores in both the treatment and control groups are normally distributed.

CBT augmented with biofeedback or relaxation therapy had a modelled risk difference for achieving the minimally important difference in pain relief of 36% (95% CI 33 to 39).

“cognitive behavioural therapy (CBT) augmented with biofeedback or relaxation therapy (modelled risk difference (RD) for achieving the minimally important difference in pain relief of 1 cm on a 10 cm scale 36% (95% CI 33 to 39))”

In subgroup analysis, longer follow-up was associated with smaller treatment effects for pain relief for removeable occlusal splint versus usual care.

“2) removeable occlusal splint versus usual care, which showed longer follow-up was associated with smaller treatment effects for pain relief”

The certainty in effects among interventions other than the most effective therapies was low or very low.

“The certainty in effects, among other interventions, was low or very low.”

This network meta-analysis has improved the precision associated with the effect of cognitive behavioural therapy for chronic temporomandibular disorder pain by augmenting direct evidence with indirect evidence.

“Our NMA has improved the precision associated with the effect of CBT for chronic TMD pain by augmenting direct evidence with indirect evidence.”

Manual trigger point therapy had a modelled risk difference for achieving the minimally important difference in pain relief of 32% (95% CI 29 to 34).

“manual trigger point therapy (RD 32% (29 to 34))”

Prior network meta-analyses included only nine to 57 randomised controlled trials, versus the 210 unique trials considered in this review.

“they included only nine to 57 RCTs, versus the 210 unique trials considered in our review.”

Cognitive behavioural therapy had a modelled risk difference for achieving the minimally important difference in pain relief of 30% (95% CI 23 to 35).

“cognitive behavioural therapy (RD 30% (23 to 35))”

Interventional trials for chronic temporomandibular disorders consistently reported effects only on pain and, to a lesser extent, physical function.

“interventional trials for chronic TMD consistently reported effects only on pain and, to a lesser extent, physical function.”

Several interventions commonly in use for chronic temporomandibular disorder pain are supported by only low or very low certainty evidence.

“Several interventions commonly in use for chronic TMD pain are supported by only low or very low certainty evidence.”

Usual care had a modelled risk difference for achieving the minimally important difference in pain relief of 25% (95% CI 22 to 28).

“usual care (such as home exercises, stretching, reassurance, self massage, and education) (RD 25% (22 to 28))”

Prior meta-epidemiological studies showed no systematic difference in estimated treatment effect between trials with and without blinded patients, healthcare providers, or outcome assessors.

“prior meta-epidemiological studies which showed no systematic difference in estimated treatment effect between trials with and without blinded patients, healthcare providers, or outcome assessors, [22][23][24][25][26]”

• cites [22][23][24][25][26]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Previous network meta-analyses of interventions for chronic TMD pain have focused on statistical significance without considering whether the magnitude of effect is patient-important.

“focusing on statistical significance without considering whether the magnitude of effect is patient-important, [6][7][8][9][10][11][12][13][14]”

• cites [6][7][8][9][10][11][12][13][14]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Previous network meta-analyses of interventions for chronic TMD pain have ranked treatments using the surface under the cumulative ranking curves (SUCRA) approach, which ignores the certainty of evidence and the absolute differences between treatment alternatives.

“These include ranking treatments using the”

• cites [6][7][8][9][10][11][12][13][14]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Previous network meta-analyses of interventions for chronic TMD pain have failed to assess the certainty of evidence.

“and failure to assess the certainty of evidence.8 13”

• cites 8 13Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Previous network meta-analyses of interventions for chronic TMD pain have addressed only certain categories of interventions or subtypes of TMD.

“addressing only certain categories of interventions or subtypes of TMD, 6 7 10 13 14”

• cites 6 7 10 13 14Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Previous network meta-analyses of interventions for chronic TMD pain have had suboptimal reporting of pooled estimates, such as pooling different instruments that measure a common domain as the standard mean difference or only pooling trials that report the same continuous outcome measure.

“suboptimal reporting of pooled estimates (such as pooling different instruments that measure a common domain as the standard mean difference, 7 8 11 only pooling trials that report the same continuous outcome measure [6][7][8][9][10][11][12][13][14] )”

• cites 7 8 11Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

The credibility of the two significant subgroup effects proved to be moderate.

“The credibility of these subgroup effects proved to be moderate (supplement table 19).”

The generalisability of the review's findings to patients with chronic temporomandibular disorder pain who also have comorbid mental illness, fibromyalgia, or rheumatoid arthritis, or who had previously undergone temporomandibular disorder surgery, is uncertain.

“because most eligible trials for our reviews excluded patients with chronic TMD pain who also had comorbid mental illness, fibromyalgia, or rheumatoid arthritis, or those who had previously undergone TMD surgery, the generalisability of our findings to these populations is uncertain.”

There was no evidence of small study effects for the three comparisons in which there were at least 10 trials available.

“We found no evidence of small study effects for the three comparisons in which there were ≥10 trials available (supplement table 20).”

In this large network meta-analysis of randomised controlled trials, moderate certainty evidence or higher shows that interventions that promote coping and encourage movement and activity were most effective for reducing chronic pain associated with temporomandibular disorders.

“In this large NMA of randomised controlled trials, moderate certainty evidence or higher shows interventions that promote coping and encourage movement and activity were most effective for reducing chronic pain associated with TMD.”

Compared with placebo or sham procedures, therapist-assisted jaw mobilisation is among the most effective therapies for reducing pain in patients with chronic temporomandibular disorder pain, based on moderate certainty evidence.

“This network meta-analysis of 153 RCTs that enrolled 8713 participants provided moderate certainty evidence that, compared with placebo/sham procedures, cognitive behavioural therapy (CBT) augmented with biofeedback or relaxation therapy, therapist-assisted jaw mobilisation, and manual trigger point therapy are among the most effective therapies for reducing pain in patients with chronic TMD pain.”

The review did not find any evidence of statistical variability across treatment effects in its outcome networks and in the assessments of between-study variances within the closed loops of evidence.

“we did not find any evidence of statistical variability across treatment effects in our outcome networks and in the assessments of between-study variances within the closed loops of evidence.”

Compared with placebo or sham procedures, manual trigger point therapy is among the most effective therapies for reducing pain in patients with chronic temporomandibular disorder pain, based on moderate certainty evidence.

“This network meta-analysis of 153 RCTs that enrolled 8713 participants provided moderate certainty evidence that, compared with placebo/sham procedures, cognitive behavioural therapy (CBT) augmented with biofeedback or relaxation therapy, therapist-assisted jaw mobilisation, and manual trigger point therapy are among the most effective therapies for reducing pain in patients with chronic TMD pain.”

There was no evidence of intransitivity based on the distribution of effect modifiers across comparisons.

“There was no evidence of intransitivity based on the distribution of effect modifiers across comparisons.”

The review did not rate down trials for risk of bias for interventions in which blinding is not possible and unblinding was the only risk of bias criterion not met.

“we did not rate down trials for risk of bias for interventions in which blinding is not possible and unblinding was the only risk of bias criterion not met”

Compared with placebo or sham procedures, cognitive behavioural therapy augmented with biofeedback or relaxation therapy is among the most effective therapies for reducing pain in patients with chronic temporomandibular disorder pain, based on moderate certainty evidence.

“This network meta-analysis of 153 RCTs that enrolled 8713 participants provided moderate certainty evidence that, compared with placebo/sham procedures, cognitive behavioural therapy (CBT) augmented with biofeedback or relaxation therapy, therapist-assisted jaw mobilisation, and manual trigger point therapy are among the most effective therapies for reducing pain in patients with chronic TMD pain.”

Four studies evaluating arthrocentesis with or without co-interventions that reported no adverse events were disconnected and thus not included in the network.

“Four studies evaluating arthrocentesis with or without co-interventions (arthrocentesis, arthrocentesis plus steroid, arthrocentesis plus opioid, ultrasound guided arthrocentesis, and arthrocentesis plus hyaluronic acid injection), and reporting no adverse events, were disconnected and thus not included in our network (supplement table 14).”