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Marked effects of tachykinin in myositis both in the experimental side and contralaterally: studies on NK-1 receptor expressions in an animal model
Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Idrottsmedicin.
Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
2013 (Engelska)Ingår i: ISRN Inflammation, ISSN 2090-8695, Vol. 2013, nr 907821Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Muscle injury and inflammation (myositis) in a rabbit model of an unilateral muscle overuse were examined. It is unknown if the tachykinin system has a functional role in this situation. In this study, therefore, the neurokinin-1 receptor (NK-1R) expression patterns were evaluated. White blood cells, nerve fascicles, fine nerve fibers, and blood vessel walls in myositis areas showed NK-1R immunoreaction. NK-1R mRNA reactions were observable for white blood cells and blood vessel walls of these areas. NK-1R immunoreaction and NK-1R mRNA reactions were also seen for muscle fibers showing degenerative and regenerative features. There were almost no NK-1R immunoreactions in normal muscle tissue. Interestingly, marked NK-1R expressions were seen for myositis areas of both the experimental side and the contralateral nonexperimental side. EIA analyses showed that the concentration of substance P in the muscle tissue was clearly increased bilaterally at the experimental end stage, as compared to the situation for normal muscle tissue. These observations show that the tachykinin system is very much involved in the processes that occur in muscle injury/myositis. The effects can be related to proinflammatory effects and/or tissue repair. The fact that there are also marked NK-1R expressions contralaterally indicate that the tachykinin system has crossover effects.

Ort, förlag, år, upplaga, sidor
2013. Vol. 2013, nr 907821
Nationell ämneskategori
Cell- och molekylärbiologi Idrottsvetenskap
Identifikatorer
URN: urn:nbn:se:umu:diva-68846DOI: 10.1155/2013/907821PubMedID: 24049666OAI: oai:DiVA.org:umu-68846DiVA, id: diva2:618232
Tillgänglig från: 2013-04-26 Skapad: 2013-04-26 Senast uppdaterad: 2018-06-08Bibliografiskt granskad
Ingår i avhandling
1. Cross transfer effects after unilateral muscle overuse: an experimental animal study about alterations in the morphology and the tachykinin system of muscles
Öppna denna publikation i ny flik eller fönster >>Cross transfer effects after unilateral muscle overuse: an experimental animal study about alterations in the morphology and the tachykinin system of muscles
2013 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

Unilateral exercise can produce certain contralateral strength effects. Deleterious events can be cross-transferred as well, as illustrated by a strict symmetry in some chronic inflammatory diseases. To date, knowledge on the effects of marked overuse of skeletal muscles is limited, and there is largely no information if unilateral overuse affects the contralateral muscles. In view of this, the present study was undertaken to test the hypothesis that unilateral muscle overuse causes alterations in tissue structure and the tachykinin system, with a focus on substance P (SP), not only in the exercised muscles, but also in the contralateral muscles. SP is a well-known neuromodulator that is known to be proinflammatory.

An experimental rabbit model with unilateral muscle overuse of the soleus and gastrocnemius muscles caused by exercise via electrical muscle stimulation (E/EMS) was used. In total, 40 rabbits were randomly divided into seven groups of which two groups served as controls. The rabbits were anaesthetized and then set on a “kicking machine” to perform exercise via EMS for 2h every second day. Experimental periods for groups 1-3 were 1, 3 and 6w, respectively, whereas groups 4-6 were exercised for 1w but also subjected to injections in the peritendinous tissue with SP, NaCL, Captopril (C), an ACE inhibitor, and DL-Thiorphan (Th) which inhibits the activity of neural endopeptidase. One group was not subjected to the experiment at all. The day after the last session of E/EMS, the soleus muscle and the gastrocnemius muscle from both legs were collected for analysis. Alterations in muscle structure and the tachykinin system were analyzed with enzyme and immunohistochemical techniques, in situ hybridization and EIA methods.

After 1w of E/EMS, focal areas of the exercised muscles contained a mild infiltration of inflammatory cells (myositis) and small morphological changes. After 3 and 6w of E/EMS, distinct myositis and muscle changes were bilaterally present in focal areas of both muscles. The structural changes, which mainly were observed in myositis areas, consisted of increased fiber size variability, split fibers, internal myonuclei, necrotic fibers, fibrosis, fat infiltration, and small fibers containing developmental MyHCs. Bilateral morphological changes, such as loss of axons, were also observed in nerves. In addition, expressions of tachykinin and the SP-preferred receptor, the neurokinin-1 (NK-1R), were bilaterally upregulated in nerve structures and blood vessel walls.  Infiltrating white blood cells exhibited tachykinin–like and NK-1R immunoreactivity. NK-1R immunoreactions were also found in necrotic and regenerating muscle fibers.

The concentration of tachykinin (SP) was significantly increased in both soleus and gastrocnemius muscles after E/EMS. There was a significant correlation between the two sides in concentration of tachykinin and in the intensity of tachykinin-like immunoreaction in blood vessel walls. The muscle fiber size and capillary supply of fibers were bilaterally decreased after 3w of EMS. The myositis areas contained an increased number of vessels with a larger size than capillaries, while areas with increased amount of connective tissue contained a very low number of capillaries. A bilateral fiber type shift against a lower proportion of slow MyHCI fibers and higher proportion of fast MyHCII fibers was observed in both muscles. The local injections of C+Th and SP+C+Th led to marked structural changes in the muscle tissue and marked increased NK-1R and tachykinin-like immunoreactivity in the myositis areas and increased tachykinin concentration in the tissue.

In conclusion, the repetitive unilateral muscle overuse caused by E/EMS led overtime to muscle injury and myositis. The affected areas contained both degenerative and regenerative alterations in the muscle tissue and nerves, and an upregulation of the tachykinin system. Most interestingly, the changes not only occurred in the exercised side, but also in the homologous contralateral muscles. The tachykinin system appears to be an important factor in the processes of crossover effects. 

Ort, förlag, år, upplaga, sidor
Umeå: Umeå Universitet, 2013. s. 73
Serie
Umeå University medical dissertations, ISSN 0346-6612 ; 1581
Nyckelord
Triceps surae, overuse, contralateral, muscle, muscle fiber, MyHC, capillary, tachykinin, substance P, NK-1R, inflammation
Nationell ämneskategori
Idrottsvetenskap Fysiologi
Forskningsämne
anatomi
Identifikatorer
urn:nbn:se:umu:diva-71242 (URN)978-91-7459-636-6 (ISBN)978-91-7459-635-9 (ISBN)
Disputation
2013-06-14, N320, Naturvetarhuset, Umeå Universitet, Umeå, 13:00 (Engelska)
Opponent
Handledare
Tillgänglig från: 2013-05-24 Skapad: 2013-05-23 Senast uppdaterad: 2018-06-08Bibliografiskt granskad

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