Corticosteroid preparations are the most commonly utilized injectate because of their effects as potent inhibitors of inflammation. They modify the local inflammatory response through stabilization of lysosomal membranes, inhibition of cellular metabolism (e.g., neutrophil chemotaxis and function), inhibition of polymorphonuclear leukocyte membrane microtubular function, and establishment of decreased local synovial permeability. Corticosteroids can also increase the viscosity of synovial fluid, alter production of hyaluronic acid synthesis, and change synovial fluid leukocyte activity [12], all of which may improve symptoms secondary to degenerative, inflammatory, and overuse syndromes.

Though many different preparations are available for joint and soft tissue injections, corticosteroids differ with respect to potency, solubility, and relative duration of action. The relative potency of individual corticosteroids is compared in Table 13.1 [13].

Few studies have investigated the duration of action of corticosteroid agents in joints or soft tissues. In general, the duration of effect is inversely related to the solubility of the therapeutic agent. The less soluble agents remain in the joint or soft tissue longer and provide more prolonged effect. Nevertheless, shorter acting solutions are less irritating to the joint space and less likely to produce a post-injection pain flare. Agents with low solubility should be used primarily for intra-articular therapy and should be avoided in soft tissues due to the increased risk of soft tissue atrophy from prolonged local corticosteroid action.

Intra-articular injection of hyaluronic acid is used to treat the pain associated with osteoarthritis of the knee with several randomized controlled studies showing reasonable efficacy [14]. The rationale for the use of hyalurons therapeutically is based on observations that hyaluronic acid is an important component of synovial fluid that acts as a cushion and lubricant for the joint. It serves as a major component of the extracellular matrix of the cartilage, helping to enhance the ability of cartilage to resist shear forces and maintain a resiliency to compression [15]. A systematic review published in 2006 suggests that injections with hyaluronic acid may also benefit people with osteoarthritis of the hip [4]. Intra-articular injection of hyaluronic acid into the hip joint appears to be safe and well tolerated [16], however only a small number of randomized clinical trials in humans have been published [17–19].

Local anesthetics can assist in identification of a symptomatic nociceptive structure by producing a rapid reduction in pain following injection/infiltration. Typically however, when performing intra-articular and soft tissue injections an anesthetic is mixed with a corticosteroid. Not only does this provide temporary analgesia and confirm delivery of the medication to the symptomatic structure, it dilutes the crystalline suspension of the corticosteroid and thus provides better diffusion of medication throughout the injected region. An allergic reaction to the amide local anesthetics such as lidocaine and bupivacaine is very rare.

Prolotherapy is the injection of a substance that activates the inflammatory cascade and thus induces fibroblast proliferation . One objective of proliferative therapy is to strengthen incompetent ligaments that exhibit laxity [23]. For example, a gymnast who has low back pain from a hypermobile sacroiliac joint, a series of prolotherapy treatments over the dorsal sacral ligaments may strengthen them and thereby reduce motion and pain. A second application of prolotherapy is to stimulate the repair of tendons that have undergone chronic degeneration (tendinosis), once again by inciting an inflammatory response which then reactivates the healing process [23]. A number of substances can be used for prolotherapy such as compounds containing phenol, glucose, and glycerine . Another commonly used substance is dextrose (10–12 % concentration) which is potentially less neurotoxic than phenol preparations. However, part of the pain-relieving effect of compounds containing dilute phenol might also be due to its toxic action on nociceptors [24].

The application of biologic treatments for musculoskeletal disorders is growing significantly. Platelet rich plasma (PRP) is an autologous biologic treatment utilizing the patients’ own blood plasma. The process involves injection of platelet derived growth factors that are obtained via density gradient centrifugation to remove plasma and red blood cells and to increase platelet concentration [25]. Platelets are well-known mediators of the coagulation cascade, however they also have hundreds of bioactive cytokines and growth factors that act via autocrine and paracrine mechanisms to enhance cell interaction and healing [26]. The rationale for the use of PRP is to stimulate tissue regeneration and the natural healing cascade by releasing these growth factors directly into the area of tissue damage [27].

It is important to mention that not all PRP preparations are the same and formulations vary in the concentration of platelets and leukocytes. This variability has made it difficult to compare PRP treatments between investigational studies. A classification system has been proposed that incorporates white blood cell concentration (increased vs. not increased over baseline), platelet concentration (greater or less than 5 times baseline), and platelet activation status [28]. Such classification allows researchers to standardize formulations of PRP for various treatment populations.

More substantiated clinical data is needed to improve our understanding of the best use of this treatment modality. Further research efforts are aimed at determining appropriate indications, type of PRP formulation, and timing/number of injections. Currently accepted indications for PRP include the treatment of chronic tendinopathies, muscle strains, and ligament injuries that have been resistant to standard medical and rehabilitative therapies [29–33]. More research is also needed to determine if there is a role for PRP to treat acute sports injuries in order to speed recovery and decrease the time missed from athletic competition [34, 35].

PRP is also being investigated as a tool for the management of knee osteoarthritis . An increasing number of clinical trials show increased function and decreased pain in the treatment of the arthritic knee [36–39]. With regard to osteoarthritis treatment, PRP is being looked at for its potential to increase anabolic effect on chondrocytes and a decrease catabolic effect in the inflammatory environment [40]. A meta-analysis on the use of PRP for the treatment of knee arthritis demonstrated better pain relief and functional improvement when compared to hyaluronic acid and placebo [41]. While the use of PRP in treatment of knee osteoarthritis seems promising, randomized controlled studies need to be initiated to explore the efficacy in other joints such as the hip.

Mesenchymal stem cells (MSCs) are another therapy which has received increased attention for not only musculoskeletal care but also in many areas of regenerative medicine. MSCs are being considered as a potential treatment for osteoarthritis because of their healing potential and anti-inflammatory effects [42]. Animal studies with MSCs used in the treatment of osteoarthritis show potential to slow down the progression of cartilage degeneration [43–46]. MSCs can modulate the inflammatory response , inhibit apoptosis, stimulate cell repair, and improve blood flow to joints [47]. By secreting paracrine factors, including cytokines and growth factors, MSCs can target injured tissues leading to a trophic effect that can initiate endogenous tissue repair [48].

MSCs are easily found in various tissue sources including bone marrow, adipose cells, periosteum, umbilical cord tissue, and synovial tissue [49]. MSCs have the capacity to differentiate into a variety of cell types. Bone marrow derived MSCs can differentiate into cells of chondrogenic lineage [46].

FDA guidelines explicitly dictate the extent to which stem cell-based therapies may be administered in clinical practice in the USA. FDA Tissue Regulation, 21 CFR Part 1271, outlines the guidelines for cell-based therapies that may be used by clinicians. These guidelines require that cells “be minimally manipulated,” “used within a short period of time,” and “be used only at the point of care.” Minimal manipulation of cells at present does not allow for extended ex-vivo culturing of cells and treatment with growth factors [49, 50].

MSCs are in their infancy with respect to their role in modulating pain and the potential for treating articular cartilage degeneration . Well-designed clinical studies are needed to not only determine efficacy, but also to determine variables such as optimal concentration of MSCs , best source to harvest them, and the safety of both autologous and allogenic sources [51, 52].

As previously discussed, the physician should review the rationale for the procedure and obtain written informed consent. In July 2004, the Joint Commission on the Accreditation of Healthcare Organizations (JCAHO ) began requiring providers to follow a universal protocol for preventing wrong site, wrong procedure, and wrong person surgery. The protocol’s three major elements include: (1) initial verification of the intended patient, procedure, and the site of the procedure; (2) marking the intended site with a sterile pen, where applicable; and (3) a final “time-out” immediately before beginning the procedure [57].