Manual Therapy Research Methods in Animal Models, Focusing on Soft Tissues.

Manual therapies have been practiced for centuries, yet little research has been performed to understand their efficacy and almost no animal research has been performed to inform mechanisms of action. The methods of manual therapy practice are quite varied and present a challenge for scientists to model the treatments and perform research using rodents. In this perspective we present a descriptive analysis of the complexity of the treatments, highlighting the role of tissue mechanics and physics. With these complexities in mind, we compare using manual therapy as clinically practiced, to attempts to develop machinery to model or mimic manual therapy. We propose that because of the complexities of manual therapy as practiced, having therapists perform the treatments on research animals just as they would on humans is the most scientific approach. Our results using this approach have supported its practicality.

Manual therapy prevents onset of nociceptor activity, sensorimotor dysfunction, and neural fibrosis induced by a volitional repetitive task.

Painful and disabling musculoskeletal disorders remain prevalent. In rats trained to perform repetitive tasks leading to signs and dysfunction similar to those in humans, we tested whether manual therapy would prevent the development of the pathologies and symptoms. We collected behavioral, electrophysiological, and histological data from control rats, rats that trained for 5 weeks before performing a high-repetition high-force (HRHF) task for 3 weeks untreated, and trained rats that performed the task for 3 weeks while being treated 3x/week using modeled manual therapy (MMT) to the forearm (HRHF + MMT). The MMT included bilateral mobilization, skin rolling, and long axis stretching of the entire upper limb. High-repetition high-force rats showed decreased performance of the operant HRHF task and increased discomfort-related behaviors, starting after training. HRHF + MMT rats showed improved task performance and decreased discomfort-related behaviors compared with untreated HRHF rats. Subsets of rats were assayed for presence or absence of ongoing activity in C neurons and slow Aδ neurons in their median nerves. Neurons from HRHF rats had a heightened proportion of ongoing activity and altered conduction velocities compared with control and MMT-treated rats. Median nerve branches in HRHF rats contained increased numbers of CD68 macrophages and degraded myelin basic protein, and showed increased extraneural collagen deposition, compared with the other groups. We conclude that the performance of the task for 3 weeks leads to increased ongoing activity in nociceptors, in parallel with behavioral and histological signs of neuritis and nerve injury, and that these pathophysiologies are largely prevented by MMT.

A Novel Method for Evaluating Postoperative Adhesions in Rats.

Purpose/Aim: Postoperative adhesions remain an undesirable and commonly symptomatic side effect of abdominopelvic surgeries. Animal models of postoperative adhesions typically yield heterogeneous adhesions throughout the abdominal cavity and are not easily quantified. Here we present a novel method of postoperative adhesion assessment and report its reliability and measurement error. MATERIALS AND METHODS: A model of cecal abrasion with partial sidewall attachment was performed on female rats. After 1, 2, 4, or 7 days of recovery, the rats were euthanized and their abdominopelvic cavities were systematically evaluated for postoperative adhesions. The necropsy was recorded through the surgical microscope. Four raters were trained to use a ballot to capture key factors of the adhesions as they viewed the recordings. Their ratings were compared for measurement error and reliability (using Bland-Altman plots and intraclass correlation coefficients, respectively) and for the ability to discriminate differences in experimental groups. A subset of the data was analyzed to determine practical utility. RESULTS: The rating system was shown to have low measurement error and high inter-rater reliability for all parameters measured. Applied practically, the system was able to discriminate groups in a manner that was expected. CONCLUSIONS: We have developed and validated a rating system for postoperative adhesions and shown that it can detect group differences. This method can be used to quantify postoperative adhesions in rodent models.

Attenuation of postoperative adhesions using a modeled manual therapy.

Postoperative adhesions are pathological attachments that develop between abdominopelvic structures following surgery. Considered unavoidable and ubiquitous, postoperative adhesions lead to bowel obstructions, infertility, pain, and reoperations. As such, they represent a substantial health care challenge. Despite over a century of research, no preventive treatment exists. We hypothesized that postoperative adhesions develop from a lack of movement of the abdominopelvic organs in the immediate postoperative period while rendered immobile by surgery and opiates, and tested whether manual therapy would prevent their development. In a modified rat cecal abrasion model, rats were allocated to receive treatment with manual therapy or not, and their resulting adhesions were quantified. We also characterized macrophage phenotype. In separate experiments we tested the safety of the treatment on a strictureplasty model, and also the efficacy of the treatment following adhesiolysis. We show that the treatment led to reduced frequency and size of cohesive adhesions, but not other types of adhesions, such as those involving intraperitoneal fatty structures. This effect was associated with a delay in the appearance of trophic macrophages. The treatment did not inhibit healing or induce undesirable complications following strictureplasty. Our results support that that maintained movements of damaged structures in the immediate postoperative period has potential to act as an effective preventive for attenuating cohesive postoperative adhesion development. Our findings lay the groundwork for further research, including mechanical and pharmacologic approaches to maintain movements during healing.

Visceral massage reduces postoperative ileus in a rat model.

OBJECTIVE: Abdominal surgery invariably causes a temporary reduction of normal intestinal motility, called postoperative ileus. Postoperative ileus extends hospital stays, increases the costs of hospitalization, and may contribute to the formation of postoperative adhesions. We designed experiments to determine if visceral massage affects postoperative ileus in a rat model. MATERIAL AND METHODS: Forty female Long Evans rats were assigned to 4 groups in a 2 (surgery) × 2 (treatment) factorial design. Twenty rats were subjected to a small intestinal manipulation designed to emulate "running of the bowel." Transabdominal massage was performed upon 10 operated and 10 control rats in the first 12 h following surgery. Ileus was assayed after 24 h using fecal pellet discharge and gastrointestinal transit. Intraperitoneal inflammation was assayed using total intraperitoneal protein and inflammatory cell concentrations. RESULTS: The surgery consistently caused ileus. Compared to the operated group with no treatment, the operated with treatment group showed increased gastrointestinal transit and reduced time to first fecal pellet discharge. Similar group comparisons revealed that the treatment decreased total intraperitoneal protein and numbers of intraperitoneal inflammatory cells. CONCLUSIONS: In this rat model, visceral massage reduced experimental postoperative ileus. The data suggest that the effect was through the attenuation of inflammation. A similar study could be designed and performed in a hospital setting to assess the potential role of visceral massage as part of the integrated care for postoperative ileus.

Visceral mobilization can lyse and prevent peritoneal adhesions in a rat model.

OBJECTIVE: Peritoneal adhesions are almost ubiquitous following surgery. Peritoneal adhesions can lead to bowel obstruction, digestive problems, infertility, and pain, resulting in many hospital readmissions. Many approaches have been used to prevent or treat adhesions, but none offer reliable results. A method that consistently prevented or treated adhesions would benefit many patients. We hypothesized that an anatomically-based visceral mobilization, designed to promote normal mobility of the abdominal contents, could manually lyse and prevent surgically-induced adhesions. MATERIAL AND METHODS: Cecal and abdominal wall abrasion was used to induce adhesions in 3 groups of 10 rats (Control, Lysis, and Preventive). All rats were evaluated 7 days following surgery. On postoperative day 7, unsedated rats in the Lysis group were treated using visceral mobilization, consisting of digital palpation, efforts to manually lyse restrictions, and mobilization of their abdominal walls and viscera. This was followed by immediate post-mortem adhesion evaluation. The rats in the Preventive group were treated daily in a similar fashion, starting the day after surgery. Adhesions in the Control rats were evaluated 7 days after surgery without any visceral mobilization. RESULTS: The therapist could palpate adhesions between the cecum and other viscera or the abdominal wall. Adhesion severity and number of adhesions were significantly lower in the Preventive group compared to other groups. In the Lysis and Preventive groups there were clear signs of disrupted adhesions. CONCLUSIONS: These initial observations support visceral mobilization may have a role in the prevention and treatment of post-operative adhesions.