The role of tryptophan and its derivatives in musculoskeletal pains: A systematic review and meta-analysis.

BACKGROUND: Studies present ambiguous findings regarding the role of tryptophan and its metabolites, kynurenine and serotonin in chronic musculoskeletal pain. This systematic review aimed to investigate the expression of tryptophan and its metabolites, serotonin and kynurenine in patients with local and generalized chronic musculoskeletal pain in comparison with pain-free controls. METHODS: An electronic search was conducted in the databases MEDLINE, CINAHL, EMBASE, the Cochrane Central Registry of Controlled Trials (CENTRAL) and Web of Science for clinical and observational trials from the beginning of each database to 21 April 2023. Out of 6734 articles, a total of 17 studies were included; 12 studies were used in the meta-analysis of serotonin, 3 regarding tryptophan and 2 studies for a narrative synthesis regarding kynurenine. Risk of bias was assessed using the quality assessment tool for observational cohort and cross-sectional studies of the National Heart, Lung, and Blood Institute, while the certainty of evidence was by GRADE. RESULTS: All included studies showed a low risk of bias. The meta-analysis showed lower blood levels of tryptophan (p < .001; very low quality of evidence) and higher blood levels of serotonin (p < .001; very low-quality evidence) in patients with generalized musculoskeletal pain, when compared to pain-free individuals. In local chronic musculoskeletal pain, there were higher blood levels of serotonin (p=.251; very low quality of evidence) compared to pain-free individuals. Regarding kynurenine, the studies reported both higher and lower blood levels in generalized chronic musculoskeletal pain compared to pain-free individuals. CONCLUSIONS: The blood levels of tryptophan and its metabolites serotonin and kynurenine seem to influence chronic musculoskeletal pain.

Pharmacological Treatments of Temporomandibular Disorders: A Systematic Review Including a Network Meta-Analysis.

OBJECTIVE: Temporomandibular disorders (TMD) comprise a cluster of conditions with a wide range of etiological factors that causes pain and discomfort in the masticatory muscles (TMD-M) and temporomandibular joints (TMD-J). More than 50% of the patients with TMD report regular usage of drugs. However, there is still no consensus, nor is there any evidence-based support for clinicians when choosing between different drugs. Therefore, this systematic review, including a network meta-analysis (NMA), aimed to evaluate the scientific evidence and discuss the pharmacological treatment options available to treat painful TMD. METHOD: An electronic search was undertaken to identify randomized controlled trials (RCTs) investigating pharmacological treatments for TMD-M and/or TMD-J, published until 6 April 2023. Since only 11 articles could be used for an NMA regarding TMD-M, a narrative synthesis was also performed for all 40 included RCTs. The quality of evidence was rated according to Cochrane's tool for assessing risk of bias, while the certainty of evidence was rated according to Grading of Recommendations Assessment, Development and Evaluation (GRADE). RESULTS: When it comes to TMD-M, evidence arises for wet needling therapies with BTX-A, granisetron, and PRP as well as muscle relaxants. For TMD-J, evidence points toward pharmacological treatment approaches including non-steroidal antiinflammatory drugs (NSAIDs) and glucocorticosteriods (for inflammatory conditions) as well as hyaluronic acid and dextrose. CONCLUSIONS: The evidence clearly indicates that the pharmacological treatment approaches differ between TMD-M and TMD-J. Therefore, it is of great importance to first try to uncover each patient's individual and multifactorial etiology and then employ a multifaceted treatment strategy, including pharmacological treatment approaches.

Clinical aspects of mastication myalgia-an overview.

Mastication myalgia is the most common cause of non-odontogenic pain in the orofacial region and is often associated with a reduced quality of life. The purpose of this review is to provide an overview of the clinical aspects of myalgia based on available research. The review includes epidemiological, diagnostic, and etiological aspects. In addition, the potential risk factors related to the transition from acute to chronic myalgia are explored and treatment strategies are presented for its management. As a result, this review may increase clinical knowledge about mastication myalgia and clarify strategies regarding prevention, diagnostics, and management to improve prognosis and reduce patient suffering.

Comorbid Conditions in Temporomandibular Disorders Myalgia and Myofascial Pain Compared to Fibromyalgia.

The impact of comorbidities in fibromyalgia (FM) and temporomandibular disorders (TMD) have been well documented, but whether TMD sub-diagnoses myalgia (MYA) and myofascial pain with referral (MFP) differ regarding comorbidity is unclear. We aimed to elucidate this by studying the presence and associations of comorbidities in FM, MFP and MYA. An extended version of the Diagnostic Criteria for TMD axis II questionnaire was used to examine demographics, pain and comorbidities in 81 patients with FM, 80 with MYA, and 81 with MFP. Patients with MFP and FM reported a higher percentage of irritable bowel syndrome (IBS), depression, anxiety, somatic symptoms, perceived stress, and insomnia compared to MYA. Patients with FM had more IBS, depression, and somatic symptom disorder versus MFP. After adjusting for confounding variables, participants with anxiety, somatic symptoms disorder, pain catastrophizing, and perceived stress, as well as a greater number of comorbidities, were more likely to have MFP than MYA, whereas FM participants were more associated with IBS, somatic symptoms and insomnia compared to MFP. The number of comorbidities was significantly associated with widespread pain but not pain duration, body mass index or being on sick leave. In conclusion, patients with MFP were more similar to those with FM regarding comorbidity and should be differentiated from MYA in clinical settings and pain management.

Plasma tryptophan and kynurenine in females with temporomandibular disorders and fibromyalgia-An exploratory pilot study.

BACKGROUND: Both temporomandibular disorders myalgia (TMDM) and fibromyalgia (FM) have been linked to central and peripheral changes in serotonin availability. The precursor of serotonin, tryptophan (TRP), is mainly catabolised via another pathway to produce kynurenine (KYN), but whether changes of this pathway are present in TMDM and FM are still unclear. OBJECTIVE: The aim was to explore blood plasma concentrations of TRP and KYN in TMDM and FM in an attempt to identify novel associations for future research. METHODS: Plasma of 113 female participants (17 TMDM, 40 FM and 56 healthy pain-free controls) were analysed for TRP and KYN concentrations. The degradation of TRP via the KYN pathway was indicated by the KYN to TRP ratio (KYN/TRP). Pain intensities were assessed with the Graded Chronic Pain Scale (GCPS) and Visual Analogue Scale (VAS). Psychological symptoms were evaluated using the Hospital Anxiety and Depression Scale (HADS), Patient Health Questionnaire (PHQ-9) and General Anxiety Disorder scale (GAD-7). RESULTS: In TMDM there was a negative correlation between TRP and pain intensity (rs  = -0.55 P = .023) and positive correlations between KYN/TRP and pain intensity (rs  = 0.59 P = .013). In FM, KYN/TRP was negatively correlated with anxiety symptoms (rs  = -0.36 P = .022) and a trend towards significantly lower TRP levels was found compared to controls (P = .05). CONCLUSION: The association between KYN/TRP and pain intensity as well as anxiety ratings in this small exploratory study may indicate that KYN/TRP could be a relevant indicator for symptom severity in TMDM and FM. Further investigations of the KYN pathway in chronic myalgia are warranted.