**3.7 Mitochondrial myopathy**

In a study of mitochondrial myopathy that included four patients, no significant differences were found for metabolites, glutamate, hypoxanthine, urate, and aspartate (**Table 7**).

### **3.8 Chronic tendinosis**

We also found three studies that focused on chronic tendinosis (**Table 8**). These three studies are small and have investigated different tendons with pain. The interstitial concentrations of glutamate, PGE2, and lactate were investigated, but no consistent pattern with respect to these substances was found.

alterations in cytokines but also to some extent in algesic substances such as glutamate in two muscles. These two studies also reported 5-HT in one muscle and in BKN in one

> Results (Comparisons between patients

Comments (Compensated for RR (Y/N) or low flow rate\*

(NA or Y/N)

RR: Y Low flow: NA

Compensated for

Compensated for

RR: Y Low flow: NA

and HC; p-values)

ns

ns

ns

Pyruvate-trapezius:

Glucose-trapezius:

Urea-trapezius: ns

Lactate- trapezius:

Glutamatetrapezius: ns K+-trapezius: ns BKN-trapezius: ns PGE2-trapezius: ns ATP-trapezius: ns

muscle. Interestingly, all alterations were normalized after prednisolone treatment.

Substances investigated Flow rate

Pyruvate Glucose Urea Glutamate

K+ BKN PGE2 ATP 2µl/min

Lactate

2µl/min

Table 5. Studies of chronic tension type headaches. The results of the different substances

In a study of mitochondrial myopathy that included four patients, no significant differences

We also found three studies that focused on chronic tendinosis (**Table 8**). These three studies are small and have investigated different tendons with pain. The interstitial concentrations of glutamate, PGE2, and lactate were investigated, but no consistent pattern

were found for metabolites, glutamate, hypoxanthine, urate, and aspartate (**Table 7**).

\*Low flow rate associated with 100% relative recovery was defined as 0.3µl/min.

are baseline data. Healthy controls are abbreviated as HC.

Study Condition

Ashina et al. (Ashina et al., 2003)

Ashina et al. (Ashina et al., 2002)

Number of Subjects, % women (W) Muscles

Chronic tension-type

Chronic tension-type

Headache (CTTH; n=16), 63% W HC (n=17), 71% W Trapezius

**3.7 Mitochondrial myopathy** 

with respect to these substances was found.

**3.8 Chronic tendinosis** 

Headache (CTTH; n=16),

63% W HC (n=17), 71% W Trapezius


\*Low flow rate associated with 100% relative recovery was defined as 0.3µl/min.

Table 6. Studies of Polymyalgia rheumatica. The results of the different substances are baseline data. Healthy controls are abbreviated as HC.

Potential Muscle Biomarkers of Chronic Myalgia in Humans –

**4. Discussion 4.1 Metabolites** 

Larsson et al., 2004).

mitochondria.

**4.2.1 Glutamate** 

**4.2 Pain-related substances** 

RR and their results might be biased.

A Systematic Review of Microdialysis Studies 119

The majority of studies concerning the trapezius in chronic trapezius myalgia have reported increases in the interstitial concentrations of lactate and pyruvate (Flodgren et al., 2010; Flodgren et al., 2006; Larsson et al., 2008; Rosendal et al., 2004b; Sjogaard et al., 2010). However, Flodgren et al. (Flodgren et al., 2010; Flodgren et al., 2006) did not compensate for

There are several possible explanations for the generally higher interstitial levels of pyruvate levels in chronic trapezius myalgia and in the trapezius of patients with FMS. For example, changes in the lactate-pyruvate metabolism via lactate dehydrogenase isoforms may result in higher pyruvate levels (Philip et al., 2005). Another explanation is a reduction in tissue oxygenation in FMS (Bengtsson, 2002) and chronic trapezius myalgia (Larsson et al., 2004), reductions that may result in higher pyruvate and higher lactate concentrations due to a shift towards an anaerobic state. A lower fitness level is a third explanation as a low fitness level means more frequent reliance on anaerobic metabolism. However, it is unknown if a general deconditioning in these two pain conditions involves the postural trapezius. The aerobic capacity of a muscle is largely governed by the number of mitochondria and their enzymes (Weibel & Hoppeler, 2005). The mitochondrial density increases as result of exercise and this increased density affects the level of metabolites (i.e., enhanced aerobic capacity) (Norrbom, 2008). Lower capillary density and/or enzymes associated with aerobic metabolism have been reported in FMS and in chronic trapezius myalgia (Larsson et al., 2004; Lindh et al., 1995). For FMS and chronic trapezius myalgia, the trapezius muscle fibres can appear with alterations in mitochondrial content and distribution, e.g., moth-eaten fibres and ragged red-fibres (Bengtsson, 2002; Bengtsson et al., 1986; Larsson et al., 2000;

The role of lactate is complex. Lactate may assist in the detection of exercise stress before tissue damage occurs and can be exchanged rapidly among tissue compartments where it may be oxidized as a fuel or reconverted to form pyruvate or glucose (Gladden, 2004; Kim et al., 2007; Philip et al., 2005; Robergs et al., 2004). Lactate is also involved in peripheral nociception and it appears to facilitate the response of the acid-sensing ion channel 3 (ASIC-3) to low pH (Kim et al., 2007). Such ASIC channels are considered to be molecular

To summarize, most studies of myalgic trapezius muscles show significant increases in interstitial levels of lactate and pyruvate. These results might be explained by decreased fitness level, reduced tissue oxygenation, increased muscle activation, and/or damaged

Two of the studies of chronic trapezius myalgia (Larsson et al., 2008; Rosendal et al., 2004b), which are markedly larger than the third study (Flodgren et al., 2005), found significant increases in the interstitial concentrations of glutamate. A possible difference between subjects of these studies may contribute to the inconsistent glutamate finding. The myalgic

transducers for nociception and mechanosensation (Kim et al., 2007).


\*Low flow rate associated with 100% relative recovery was defined as 0.3µl/min.

Table 7. Studies of mitochondrial myopathy. The results of the different substances are baseline data. Healthy controls are abbreviated as HC.


\*Low flow was defined as 0.3µl/min.

Table 8. Studies of tendons with chronic pain. The results of the different substances are baseline data. Healthy controls are abbreviated as HC.
