Fibromyalgia (FM) is a disorder characterized by chronic diffuse muscle pain due to an exaggerated response to peripheral stimuli known as central sensitization [1-3]. The prevalence of FM rates varies from 2% to 11% in the general population but has predominance in middle-aged female [2,4].

FM frequently accompanies centrally mediated symptoms such as fatigue and non-restorative sleep [5]. Some patients with FM have distressing neuropsychiatric symptoms and functional impairments [2]. It is well-known that otologic symptoms such as dizziness, hearing loss, and tinnitus also often associate with FM [6,7].

The cause of tinnitus is not well known in most cases, so there is no curative treatment [8]. Recently, there is increasing evidence that changes in the central nervous system such as central gaining and centralization are associated with tinnitus [9]. But the relationship between tinnitus and FM is not well understood. In this study, we evaluated the impact of tinnitus on FM.

All 47 FM patients completed the study protocol. About 90% are women and suffered from headache. Also, about half the patients had tinnitus. Widespread moderate-to-severe pain, insomnia, and decreased quality of life were also observed (Table 1).

While we found a mildly significant difference between the 22 FM patients with tinnitus and the 25 FM patients without tinnitus with regard to SSS (p=0.051), there were no statistical differences in demographics and clinical variables between the two groups (as shown in Table 2).

Among the 22 patients who had tinnitus and FM, two did not answer the Tinnitus Handicap Questionnaire. Our study showed significant differences between patients with mild tinnitus (THQ<38) and patients with moderate-to-severe tinnitus (THQ≥38) for FIQ (p= 0.025) and the physical functioning (p=0.003), social functioning (p=0.035), and mental health (p=0.017) components of the SF-36 (Table 3). These results suggest that FM patients who had more severe tinnitus had more severe FM symptoms and suffered more negative impacts on their quality of life.

When we divided FM patients into two groups by insomnia severity (insomnia grade 1∼2 and insomnia grade 3∼4), we found significant differences in FIQ (p= 0.002) and in bodily pain (p=0.001), general health (p= 0.008), vitality (p=0.003), social functioning (p=0.003), role limitation due to emotional condition (p=0.001), and mental health (p<0.001) components of the SF-36 (Table 4). This suggests that insomnia severity has a positive correlation with FM severity and a negative correlation with quality of life in FM patients.

In this study, we evaluated the association between tinnitus severity and FM. Previous studies demonstrate that tinnitus and FM have a common pathophysiology, called central sensitization. Also, the conditions are treated with similar drugs. However, no previous studies have explored links between them.

In this study, 93.6% of the 47 FM patients were female and their mean age was 53.8±8.8 years. A recent study investigated 86 FM patients in South Korea, among whom 94.4% were female and their mean age was 50.9±11.8 years [11], which is consistent with the high prevalence of FM in middle-aged women. We showed that 46.8% and 87.2% of the 47 FM patients had tinnitus and headache, respectively, suggesting a high incidence of these symptoms in FM. Koca et al. [16] found that FM patients had more otologic symptoms, including tinnitus and high level of oxidative stress. In another study, 74.3% of 101 FM patients had tinnitus despite having audiological test results in the normal range [7]. Herein, we confirm that fibromyalgia frequently accompanies tinnitus. Furthermore, we show that the more severe is the tinnitus, the more severe are the FM symptoms and the lower is the quality of life, all of which cause limited physical activity and mood disturbance.

Our study suggests that tinnitus is a key component of centrally mediated symptoms in FM, indicating that tinnitus severity is closely related to FM severity and should be assessed in all FM patients. Due to altered neurological processing known as central sensitization, FM patients feel pain associated with peripheral nociceptive stimuli more acutely (allodynia) and more intensely (hyperalgesia) [2]. Centrally mediated symptoms such as fatigue, sleeplessness, and mood disturbance are characteristics in central sensitization [1,5]. There is some evidence that FM patients have increased activation of a pain-related brain lesion and significant imbalances among pain-processing areas and cognition-attention networks of the brain [1]. Also, evidence suggests that the activity of centrally acting neurotransmitters is altered in FM. Russell et al. [17,18] investigated the neurotransmitters in FM patients and found elevated level of substance P and reduced levels of serotonin, norepinephrine, and dopamine in the cerebrospinal fluid. Furthermore, centrally acting drugs such as serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants, and gabapentinoids are used to treat FM. These drugs not only have an analgesic effect, they also diminish centrally mediated symptoms in FM patients [5,19]. From these findings, we hypothesize that the imbalance of neurotransmitters in central sensitization plays an essential role in FM. Additionally, assuming that tinnitus is a result of imbalance in neurotransmitters, we found that FM severity correlated with tinnitus severity rather than tinnitus presence, as shown in Tables 2 and 3. Moreover, we assume that drugs taken to treat FM will also affect tinnitus. We could confirm that the rate of taking drugs such as selective serotonin reuptake inhibitors, SNRI and pregabalin was significantly higher in the moderate-to-severe tinnitus group than in the mild tinnitus group, as shown in Table 3 (p=0.042). In a single, small study that evaluated the efficacy of some FM drugs for tinnitus, pregabalin and duloxetine were found to alleviate tinnitus in FM patients but not to a statistically significant degree between pregabalin and duloxetine [7]. More research about the effectiveness of these drugs for tinnitus is needed.

Numerous studies have found that reduced input of peripheral sensory neurons activates homeostatic plasticity to result in central sensitization. Noreña and Farley [9] suggested that this process ultimately causes tinnitus, even if hearing loss is not detected in the audiogram. Additionally, centralization of tinnitus may become progressive over time, making it less dependent on peripheral sensory input. So, there is a possibility that tinnitus is one of the aggravating causes of FM, not a result of FM. Therefore, it may be appropriate to evaluate and treat tinnitus early in FM patients.

We predicted that tinnitus severity would be associated with insomnia severity in FM patients, but we found no meaningful difference between the mild tinnitus and moderate-to-severe tinnitus groups in Insomnia Severity Index scores (p=0.16; Table 3). This may be due to our small sample size. Further studies are needed to better evaluate these associations. A cross-sectional survey showed that poor quality of sleep is associated with increased pain intensity and decreased quality of life in women with FM [20]. Our study also concluded that insomnia is a significant symptom of FM and should be carefully evaluated.

To our knowledge, this is the first study of the impact of tinnitus in FM patients. We concluded that tinnitus severity is related to FM severity and lower quality of life. We also reconfirmed that insomnia severity has a positive correlation with FM severity and an inverse correlation with quality of life, as shown in Table 4. However, we found no significant correlation between tinnitus presence and FM severity.

Our study has some limitations. First, this was a study conducted in a tertiary hospital, our participants may represent a subset of patients with more severe FM symptoms than would be expected in FM patients overall. Second, we performed a single-center cross-sectional study. Third, we could not measure the hearing capacity in tinnitus group since the patients had difficulty getting a hearing test at the otolaryngology clinic for time reasons. Fourth, due to our small sample size, we used non-normal distribution tests. Further large-scale, multicenter, and cohort studies are necessary.

FM patients with severe tinnitus have more functional impairments and lower quality of life than patients with mild tinnitus. Insomnia severity also has a positive correlation with poor health status and lower quality of life in FM patients. We identified a need for early evaluation and treatment of tinnitus and the significance of insomnia in FM patients.