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Subacromial inflammation: Clinical and experimental studies
Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics. Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
2001 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Shoulder pain and disability are common clinical problems. One major cause is subacromial inflammation and impingement of the supraspinatus tendon. These patients are usually offered conservative treatment or arthroscopic subacromial decompression (ASD). However, in some patients pain and a deficient shoulder function persist in spite of conservative and surgical treatment. This reflects the fact that the pathophysiology of this important disease is not fully understood. The general aim of the present thesis was to generate new lmowledge contributing to the understanding of subacromial inflammation through a combination of clinical and experimental studies.

Ketoprofen is a non-steroid antiinflammatory drug with effects on peripherally as well as centrally generated pain. In a randomized, double-blind, prospective study on impingement patients treated with ASD, postoperative administration of ketoprofen showed short-term, but not long-term positive effects on pain, range of movement and satisfaction.

The status of the rotator cuff was found not to influence the postoperative results after ASD. Patients with an intact, partially ruptured or totally ruptured (<2cm) supraspinatus tendon did equally well, both 3 and 6 years after surgery. The results suggest that the presence of an inflamed bursa is more important for the symptoms than the cuff lesion.

In search for an experimental model we found that the shoulder region of the rat shows macroanatomical similarities to the human shoulder. Analysis of the innervation of the rat shoulder showed that the suprascapular nerve and some branches projecting to the subacromial space contain numerous C- and Ao-fibers. Many of these appeared to be polymodally nociceptive units or postganglionic sympathetic units as revealed by capsaicin and chemical sympathectomy. Such fibers are relevant for inflanunatory states.

In the normal rat substance P- (SP), calcitonin gene-related peptide- (CGRP) immunoreactive putative nociceptive fibers and neuropeptide Y- (NPY) and tyrosine hydroxylase- (TH) immunoreactive putative sympathetic fibers were widely distributed in the subacromial space. After induction of an acute subacromial inflammation with carrageenan, the presence of SP- and/or CGRP-immunoreactive fibers in the supraspinatus tendon was increased, with a maximum at two weeks. The results of labeling with the growth-associated protein GAP-43 indicated a de novo sprouting of nociceptive fibers in the tendon. But, radioimmunoassay measurements showed that the content of SP, CGRP and NPY in the supraspinatus tendon were normal or subnormal.

These results called for examination of subacromial tissue biopsies from  impingement patients. Innnunohistochemical analysis showed an increase of SP- and/or CGRP- immunoreactive nerve fibers and of NPY-immunoreactive nerve fibers in tendon tissue. The presence of corresponding neuropeptides was also elevated, as determined by RIA. The analysis also revealed an increase of SP and/or CGRP-immunoreactive nerve fibers and an elevated concentration of corresponding neuropeptides in bursal tissue.

Place, publisher, year, edition, pages
Linköping: Linköpings universitet , 2001. , 87 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 658
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-25660Local ID: 10036ISBN: 91-721-9759-5 (print)OAI: oai:DiVA.org:liu-25660DiVA: diva2:246208
Public defence
2001-02-16, Berzeliussalen, Universitetssjukhuset, Linköping, 09:00 (Swedish)
Opponent
Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2012-08-17Bibliographically approved
List of papers
1. The Clinical Effect of Ketoprofen After Arthroscopic Subacromial Decompression: A Randomized Double-Blind Prospective Study
Open this publication in new window or tab >>The Clinical Effect of Ketoprofen After Arthroscopic Subacromial Decompression: A Randomized Double-Blind Prospective Study
1999 (English)In: Arthroscopy: The Journal of Arthroscopy And Related, ISSN 0749-8063, E-ISSN 1526-3231, Vol. 15, no 3, 249-252 p.Article in journal (Refereed) Published
Abstract [en]

The purpose of the study was to evaluate the clinical effect of ketoprofen after arthroscopic subacromial decompression (ASD). The design was randomized, prospective, and double-blind, with a placebo control group. Forty-one consecutive patients with subacromial impingement syndrome, were randomized to treatment with ketoprofen 200 mg once daily or placebo for 6 weeks following ASD. For additional analgesia, patients used paracetamol if necessary. Clinical follow-up was performed at 6 weeks and at 2 years postoperatively. At the 6-week follow-up, the patients treated with ketoprofen had a statistically significant increase in UCLA total score (P < .05), range of movement (P < .05), and satisfaction (P < .05), and they had significantly less pain (P < .05). There was no statistical difference between the ketoprofen and placebo groups regarding strength. Patients receiving ketoprofen had significantly less need for additional analgesia (P < .05). At the 2-year follow-up, there were no differences in the scores between the ketoprofen and placebo group.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-27821 (URN)10.1016/S0749-8063(99)70029-0 (DOI)12573 (Local ID)12573 (Archive number)12573 (OAI)
Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2017-12-13Bibliographically approved
2. The influence of cuff pathology on shoulder function after arthroscopic subacromial decompression: A 3- and 6-year follow-up study
Open this publication in new window or tab >>The influence of cuff pathology on shoulder function after arthroscopic subacromial decompression: A 3- and 6-year follow-up study
1999 (English)In: Journal of shoulder and elbow surgery, ISSN 1058-2746, E-ISSN 1532-6500, Vol. 8, no 6, 585-589 p.Article in journal (Refereed) Published
Abstract [en]

In the literature operative management of rotator cuff ruptures in the shoulder varies, from tendon repair to debridement of the cuff lesion combined with subacromial decompression. This study was made to evaluate whether patients with intact rotator cuff differed from patients with rotator cuff ruptures regarding functional outcome after arthroscopic subacromial decompression. We performed a clinical review of 39 patients with subacromial impingement who all underwent arthroscopic subacromial decompression; no other surgery was performed. There were 13 patients with intact cuff, 13 patients with partial-thickness supraspinatus ruptures, and 13 patients with full-thickness supraspinatus ruptures <2 cm. Selection was based solely on the status of the supraspinatus tendon. Patients with other pathologic conditions were excluded. Follow-up was performed after 3 and 6 years. The clinical evaluation was performed with the Constant score and the visual analog pain score. The 3- and 6-year follow-up (100% follow-up rate) revealed no significant difference between the groups regarding the Constant scores and the visual analog scale values. Also, no significant difference was seen among the 3 groups in active range of motion or strength, and the patients had no appreciable pain. We conclude that the functional outcome 6 years after arthroscopic subacromial decompression is not obviously related to the preoperative degree of cuff pathology, even if a total rupture of small size is present.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-49917 (URN)10.1016/S1058-2746(99)90094-0 (DOI)
Available from: 2009-10-11 Created: 2009-10-11 Last updated: 2017-12-12Bibliographically approved
3. Shoulder region of the rat: Anatomy and fiber composition of some suprascapular nerve branches
Open this publication in new window or tab >>Shoulder region of the rat: Anatomy and fiber composition of some suprascapular nerve branches
1994 (English)In: The Anatomical Record, ISSN 1932-8486, Vol. 239, no 3, 332-342 p.Article in journal (Refereed) Published
Abstract [en]

Background: The pathophysiology of chronic supraspinatus tendinitis is not fully understood. This may be due to the scarcity of experimental studies on this issue.

Methods: In search for a system suitable for experimental analysis, the present study describes the relevant gross anatomy of the rat shoulder region (dissection), and examines the fiber composition of relevant suprascapular nerve branches (electron microscopy, selective denervations).

Results: The rat shoulder region is similar to the human shoulder in terms of gross anatomy. The average suprascapular nerve (SSC) is derived mainly from the spinal cord segment C5 and contains 3,435 axons, 74% of which are unmyelinated. The supraspinatus branch (SSP) contains 627 fibers. Of the SSP fibers, 52% are myelinated, including 32% motor and 20% sensory axons. Of the C-fibers in the SSP 16% are sympathetic efferents and 32% are sensory. Many of the latter disappear after neonatal capsaicin treatment. The SSC emits a subacromial articular branch (ART), with some 260 axons, about 90% of which are unmyelinated. The myelinated ART fibers are sensory, and of the unmyelinated ones about 24% are sympathetic efferents and 66% are afferents. The latter resist neonatal capsaicin treatment.

Conclusions: In view of the anatomy of the supraspinatus muscle, of the subacromial space, and of relevant nerves, the rat shoulder should be appropriate for experimental studies on inflammatory conditions in the subacromial space.

Keyword
Rat, Shoulder region, Gross anatomy, Subacromial space, Supraspinatus muscle, Suprascapular nerve, Fiber composition, Electron microscopy
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-80033 (URN)10.1002/ar.1092390311 (DOI)
Available from: 2012-08-17 Created: 2012-08-17 Last updated: 2012-08-17Bibliographically approved
4. Acute local inflammation elicits sprouting of sensory axons in the rat supraspinatus tendon
Open this publication in new window or tab >>Acute local inflammation elicits sprouting of sensory axons in the rat supraspinatus tendon
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Inflammation activates nociceptive nerve endings and can elicit local sprouting of axons. We hypothesized that axon sprouting might be one factor behind the emergence of painful inflammatory conditions in the shoulder. Here we examine the distribution of sensory and sympathetic axons in the rat subacromial space under normal conditions and after local induction of inflammation with carrageenan. Furthermore, we measured the neuropeptide content in the supraspinatus tendon. In normal rats protein gene product 9.5- (POP 9.5-), substance P- (SP-), calcitonin gene related peptide- (CGRP-), neuropeptide Y- (NPY-) and tyrosine hydroxylase- (TH-) like immunoreactive (LI) axon profiles occurred in the subacromial space and around the glenohumeral joint. In the supraspinatus tendon axon profiles were limited to the tendon-muscle junction. After carrageenan injection inflammatory cells invaded the tendon and the subacromial bursa with a maximum at 2-3 weeks. Moreover, the tendon and the bursa showed signs of sprouting of PGP-9.5-, SP- and CGRP-LI axons, but not NPY- and TH-LI axons. The tendon was also invaded by blood vessels. The occurrence of axon profiles had a maximum at 2 weeks after injection and then subsided. Also, these axons were GAP-43-LI indicating collateral sprouting of nociceptive nerve fibres. There was no significant increase in the concentration of the neuropeptides SP and CGRP in the supraspinatus tendon. No inflammatory reaction or sprouting of nerve fibres was seen in saline-injected controls. We conclude that an acute inflammation in the subacromial space of the rat shoulder region can elicit a transient local sprouting of sensory axons in the tendon stroma and associated aberrant blood vessels.

Keyword
inflanunation, carrageenan, protein gene product 9.5, calcitonin gene related peptide, neuropeptide Y, substance P, tyrosine hydroxylase, GAP-43, radioimmunoassay
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-80044 (URN)
Available from: 2012-08-17 Created: 2012-08-17 Last updated: 2012-08-17Bibliographically approved
5. Increased Occurrence of Nerve Fibres and some Neuropeptides in Subacromial Tissue Biopsies from Patients with Impingement Syndrome of the Shoulder
Open this publication in new window or tab >>Increased Occurrence of Nerve Fibres and some Neuropeptides in Subacromial Tissue Biopsies from Patients with Impingement Syndrome of the Shoulder
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Background: The pathophysiology of subacromial inflammation is not fully understood. In the present study we evaluate the presence of sensory and sympathetic nerve fibres and some neuropeptides in biopsies from the supraspinatus tendon and the subacromial bursa of patients with chronic subacromial inflammation as well as of control cases.

Methods: The occurrence of nerve fibres was subjectively assessed by immunohistochemistry. The concentration of substance P (SP), calcitonin generelated peptide (CGRP) and neuropeptide Y (NPY) was measured by radioimmunoassay (RIA).

Results: In tendon biopsies from patients with an intact or partially ruptured tendon protein gene product 9.5-like immunoreactive (LI), SP-LI and CGRP-LI nerve fibres were abnormally abundant. In patients with a total tendon rupture nerve fibre occurrence was normal. All biopsies from the bursa exhibited an abnormally high occurrence of SP- and CGRP-LI nerve fibres. In all biopsies the tendon and the bursa contained more blood vessels than normal. The vessels were surrounded by NPY- and tyrosine hydroxylase-LI nerve fibres in a subjectively normal pattern. RIA analysis revealed that the concentration of all three neuropeptides was abnormally high in tendon biopsies from patients with an intact or partially ruptured tendon. Tendon biopsies from patients with total tendon rupture showed statistically normal levels. Biopsies from the bursa showed abnormally high levels of SP and CGRP but normal levels of NPY in all patients.

Conclusion: We conclude, that the supraspinatus tendon and the subacromial bursa exhibit an increased occurrence of nerve fibres and some neuropeptides in patients with chronic subacromial inflammation.

Clinical relevance: Patients with chronic subacromial inflammation have a disabling pain problem. The increased local occurrence of sensory andsympathetic axons in the inflamed tissues as well as the elevated tissue concentration of certain neuropeptides may represent important factors behind that problem.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-80036 (URN)
Available from: 2012-08-17 Created: 2012-08-17 Last updated: 2012-08-17Bibliographically approved

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