Handbook of Pain Assessment

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a 38-amino acid peptide that was first isolated from ovine hypothalamic extracts on the basis of its ability to stimulate cAMP formation in anterior pituitary cells. PACAP belongs to the vasoactive intestinal polypeptide (VIP)-glucagon-growth hormone releasing factor-secretin superfamily. The sequence of PACAP has been remarkably well conserved during the evolution from protochordate to mammals, suggesting that PACAP is involved in the regulation of important biological functions. PACAP is widely distributed in the brain and peripheral organs, notably in the endocrine pancreas, gonads, and respiratory and urogenital tracts. Characterization of the PACAP precursor has revealed the existence of a PACAP-related peptide whose activity remains unknown. Two types of PACAP binding sites have been characterized. Type I binding sites exhibit a high affinity for PACAP and a much lower affinity for VIP whereas type II binding sites have similar affinity for PACAP and VIP. Molecular cloning of PACAP receptors has shown the existence of three distinct receptor subtypes, the PACAP-specific PAC1 receptor, which is coupled to several transduction systems, and the two PACAP/VIP-indifferent VPAC1 and VPAC2 receptors, which are primarily coupled to adenylyl cyclase. PAC1 receptors are particularly abundant in the brain and pituitary and adrenal glands whereas VPAC receptors are expressed mainly in the lung, liver, and testis. The wide distribution of PACAP and PACAP receptors has led to an explosion of studies aimed at determining the pharmacological effects and biological functions of the peptide. This report reviews the current knowledge concerning the multiple actions of PACAP in the central nervous system and in various peripheral organs including the endocrine glands, the airways, and the cardiovascular and immune systems, as well as the different effects of PACAP on a number of tumor cell types.

Pituitary Adenylate Cyclase-Activating Polypeptide and Its Receptors: From Structure to Functions

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a 38-amino acid C-terminally alpha-amidated peptide that was first isolated 20 years ago from an ovine hypothalamic extract on the basis of its ability to stimulate cAMP formation in anterior pituitary cells (Miyata et al., 1989. PACAP belongs to the vasoactive intestinal polypeptide (VIP)-secretin-growth hormone-releasing hormone-glucagon superfamily. The sequence of PACAP has been remarkably well conserved during evolution from protochordates to mammals, suggesting that PACAP is involved in the regulation of important biological functions. PACAP is widely distributed in the brain and peripheral organs, notably in the endocrine pancreas, gonads, respiratory and urogenital tracts. Characterization of the PACAP precursor has revealed the existence of a PACAP-related peptide, the activity of which remains unknown. Two types of PACAP binding sites have been characterized: type I binding sites exhibit a high affinity for PACAP and a much lower affinity for VIP, whereas type II binding sites have similar affinity for PACAP and VIP. Molecular cloning of PACAP receptors has shown the existence of three distinct receptor subtypes: the PACAP-specific PAC1-R, which is coupled to several transduction systems, and the PACAP/VIP-indifferent VPAC1-R and VPAC2-R, which are primarily coupled to adenylyl cyclase. PAC1-Rs are particularly abundant in the brain, the pituitary and the adrenal gland, whereas VPAC receptors are expressed mainly in lung, liver, and testis. The development of transgenic animal models and specific PACAP receptor ligands has strongly contributed to deciphering the various actions of PACAP. Consistent with the wide distribution of PACAP and its receptors, the peptide has now been shown to exert a large array of pharmacological effects and biological functions. The present report reviews the current knowledge concerning the pleiotropic actions of PACAP and discusses its possible use for future therapeutic applications.

Pituitary Adenylate Cyclase-Activating Polypeptide and Its Receptors: 20 Years after the Discovery

Overuse tendinopathy is problematic to manage clinically. People of different ages with tendons under diverse loads present with varying degrees of pain, irritability, and capacity to function. Recovery is similarly variable; some tendons recover with simple interventions, some remain resistant to all treatments. The pathology of tendinopathy has been described as degenerative or failed healing. Neither of these descriptions fully explains the heterogeneity of presentation. This review proposes, and provides evidence for, a continuum of pathology. This model of pathology allows rational placement of treatments along the continuum. A new model of tendinopathy and thoughtful treatment implementation may improve outcomes for those with tendinopathy. This model is presented for evaluation by clinicians and researchers.

https://bjsm.bmj.com/content/bjsports/43/6/409.full.pdf

Is tendon pathology a continuum? A pathology model to explain the clinical presentation of load-induced tendinopathy

https://espace.library.uq.edu.au/view/UQ:225158/UQ225158_OA.pdf

Efficacy and safety of corticosteroid injections and other injections for management of tendinopathy: a systematic review of randomised controlled trials

Background Arthroscopic partial meniscectomy is one of the most common orthopedic procedures, yet rigorous evidence of its efficacy is lacking. Methods We conducted a multicenter, randomized, double-blind, sham-controlled trial in 146 patients 35 to 65 years of age who had knee symptoms consistent with a degenerative medial meniscus tear and no knee osteoarthritis. Patients were randomly assigned to arthroscopic partial meniscectomy or sham surgery. The primary outcomes were changes in the Lysholm and Western Ontario Meniscal Evaluation Tool (WOMET) scores (each ranging from 0 to 100, with lower scores indicating more severe symptoms) and in knee pain after exercise (rated on a scale from 0 to 10, with 0 denoting no pain) at 12 months after the procedure. Results In the intention-to-treat analysis, there were no significant between-group differences in the change from baseline to 12 months in any primary outcome. The mean changes (improvements) in the primary outcome measures were as follows: Lysholm score, 21.7 points in the partial-meniscectomy group as compared with 23.3 points in the sham-surgery group (between-group difference, −1.6 points; 95% confi dence interval [CI], −7.2 to 4.0); WOMET score, 24.6 and 27.1 points, respectively (between-group difference, −2.5 points; 95% CI, −9.2 to 4.1); and score for knee pain after exercise, 3.1 and 3.3 points, respectively (between-group difference, −0.1; 95% CI, −0.9 to 0.7). There were no significant differences between groups in the number of patients who required subsequent knee surgery (two in the partialmeniscectomy group and five in the sham-surgery group) or serious adverse events (one and zero, respectively). Conclusions In this trial involving patients without knee osteoarthritis but with symptoms of a degenerative medial meniscus tear, the outcomes after arthroscopic partial meniscectomy were no better than those after a sham surgical procedure. (Funded by the Sigrid Juselius Foundation and others; ClinicalTrials.gov number, NCT00549172.)

/pdf/arthroscopic-partial-meniscectomy-versus-sham-surgery-for-a-5e819dn5r1.pdf

Arthroscopic Partial Meniscectomy versus Sham Surgery for a Degenerative Meniscal Tear

To determine the long-term outcome of patients treated nonoperatively for acute or subchronic (duration of the symptoms before initiation of the treatment less than 6 months) Achilles tendinopathy, we performed a follow-up analysis on 83 of 107 patients an average 8 +/- 2 (SD) years after the initial contact. The analysis included a questionnaire, clinical examination, performance tests, muscle strength measurement, and ultrasonographic examination. Twenty-four of the 83 patients (29%) had to be operated on during the follow-up period. Seventy patients (84%) had full recovery of their activity level, and at 8 years' follow-up 78 patients (94%) were asymptomatic or had only mild pain with strenuous exercise. However, a clear side-to-side difference between the involved and the uninvolved sides was observed on the performance test, clinical examination, and ultrasonography. Also, 34 patients (41%) started to suffer from overuse symptoms in the initially uninvolved Achilles tendon. The results of our 8-year follow-up showed that the long-term prognosis of patients with acute-to-subchronic Achilles tendinopathy is favorable as determined by subjective and functional assessments. In the clinical and ultrasonographic examinations, mild-to-moderate changes were observed rather frequently in both the involved and initially uninvolved Achilles tendons, but the occurrence of these changes was not clearly related to the patients' symptoms.

Long-Term Prognosis of Patients With Achilles Tendinopathy An Observational 8-Year Follow-up Study

We analyzed the complications after surgical treatment of Achilles tendon overuse injuries in 432 consecutive patients. The patients underwent a clinical examination 2 weeks, and 1, 2, and 5 months after the surgery. If a complication appeared, the patient was followed up clinically for at least 1 year. There were 46 (11%) complications in the 432 patients: 14 skin edge necroses, 11 superficial wound infections, 5 seroma formations, 5 hematomas, 5 fibrotic reactions or scar formations, 4 sural nerve irritations, 1 new partial rupture, and 1 deep vein thrombosis. Fourteen patients with a complication had reoperations: four patients for skin edge necrosis, two for superficial wound infection, two for seroma formation, one for hematoma formation, two for fibrotic reaction or scar formation, two for sural nerve irritation, and one for a new partial rupture. About every 10th patient treated surgically for chronic Achilles tendon overuse injury suffered from a postoperative complication that clearly delayed rec...

Chronic Achilles tendon overuse injury: complications after surgical treatment. An analysis of 432 consecutive patients.

The Achilles tendon is the strongest tendon in the human body. Because most Achilles tendon injuries take place in sports and there has been an common upsurge in sporting activities, the number and incidence of the Achilles tendon overuse injuries and complete ruptures have increased in the industrialized countries during the last decades. The most common clinical diagnosis of Achilles overuse injuries is tendinopathy, which is characterized by a combination of pain and swelling in the Achilles tendon accompanied by impaired ability to perform strenuous activities. Most patients with Achilles tendon injury respond favorably to conservative treatment and only those who fail to respond to carefully followed nonoperative treatment should undergo surgery for repair. A complete rupture of the Achilles tendon usually occurs in sports that require jumping, running, and quick turns. Although histopathologic studies have shown that ruptured Achilles tendons include clear degenerative changes before the rupture, many of the Achilles tendon ruptures occur suddenly without any preceding signs or symptoms. Neither conservative nor operative treatment is a treatment of choice for the ruptured Achilles tendon. It is generally accepted that surgery should be performed on ruptured Achilles tendons in young, physically active patients and in those patients for whom the diagnosis or the treatment of the rupture has been delayed, whereas the results of conservative treatment are an acceptable outcome in older patients with sedentary lifestyles. Many important issues still remain unanswered concerning the cause, pathogenesis, diagnosis, and management of the Achilles tendon disorders. Only when these issues have been solved by well-controlled studies can tailored treatment protocols be created.

Achilles tendon injuries.

>The combination of Achilles tendon pain, swelling, and impaired performance indicates the clinical diagnosis of Achilles tendinopathy. > The chronic form of Achilles tendinopathy is not an inflammatory condition. > In its early phases, Achilles tendinopathy often responds favorably to conservative treatment with rest or modified activity, cold, stretching, nonsteroidal anti-inflammatory medications, and correction of provoking factors. > Surgery is considered an acceptable choice among patients who have failed to respond to conservative treatment. > Operative management includes longitudinal division of the crural fascia, excision of the macroscopic adhesions, and excision of any intratendinous lesion that is identified on preoperative imaging examinations or intraoperatively.

Mika Paavola

Papers

Arthroscopic Partial Meniscectomy versus Sham Surgery for a Degenerative Meniscal Tear

Long-Term Prognosis of Patients With Achilles Tendinopathy An Observational 8-Year Follow-up Study

Chronic Achilles tendon overuse injury: complications after surgical treatment. An analysis of 432 consecutive patients.

Achilles tendon injuries.

Current concepts review: Achilles tendinopathy