Inflammation is the body’s response to disease or injury of any kind. Inflammation may be a “normal” body response to injury but this response can cause far more damage than what the body intended or can handle. To reduce the deleterious effects of these processes, veterinarians often manipulate the inflammatory response with different therapeutic methods and drugs.
Inflammation is a microcirculation response to injury. The cardinal signs of inflammation are heat, redness, swelling, pain, and loss of function. When injury or invasion by microorganisms takes place to the cells of the body, there is a release of enzymes and other materials from the dead or dying cells. These enzymes and proteins act to signal the body to release white blood cells. These white blood cells migrate to the site of the injury to clean up the cellular debris caused by the injury and help start the repair process. As the white blood cells clean up the debris, they are releasing enzymes and proteins that signal for more white blood cells to come help with the cleanup. This release of enzymes and proteins is the ultimate cause of the heat, redness, and pain at the site of injury. With the migration of white blood cells to the site of injury, the blood vessels leading to the site become leaky to allow for the cells to get to the injury. This permeability of the blood vessels is the source for the fluid that causes the swelling that occurs with inflammation. The swelling also contributes to the heat, redness and pain at the site. Combining all of these processes lead to the loss of function in this area. These processes are necessary to protect the body from further injury, to clean the site from dying tissue, to promote healing and return function to the site. If the inflammatory stimulus continues to persist, if the inflammatory process becomes uncontrollable, or to enhance healing to occur more quickly, intervention in the inflammatory process is necessary and desirable. To combat inflammation several modalities are used. The anti-inflammatories used for musculoskeletal problems of the horse will be discussed.
The first and possibly most overlooked way to reduce inflammation is hydrotherapy. Cold water helps to restrict blood vessel dilation which slows the inflammatory mediators and reduces the initial swelling that can occur from acute injury. From various studies, the effectiveness of ice baths is greater than just cold water or ice packs alone. Treatment is most effective if done3-4 times a day for no longer than 30 minutes at a time. Cold-water therapy is only beneficial in the first 48 hours after injury. Moist hot packs can then be used to reduce the inflammation by increasing blood flow to the injured area after the initial 48 hours post injury. Heat also increases the metabolism of the cells in that area that helps to increase the lymphatic drainage away from the area, further reducing the swelling. Hydrotherapy is used for injury to tendons, ligaments, joints, and muscles. It will not contain all inflammation, but is a good adjunct to other modalities.
Dimethyl Sulfoxide (DMSO) is a potent anti-inflammatory agent used in the treatment of horses. Medical grade DMSO acts as a solvent that absorbs readily into the skin and can act as a carrier for other anti-inflammatory agents while having its own anti-inflammatory properties. DMSO inhibits one of the enzymes that converts a protein within the inflammation pathway. This inhibition reduces vasodilatation, which reduces the swelling and edema associated with the inflammatory process. DMSO is used for injury to tendons, ligament, joints, and muscles. Caution must be used with DMSO around open wounds, applying it to clean skin only. Also some horses are very sensitive to the heat generated when it is applied.
Non-steroidal anti-inflammatory drugs (NSAID) are the most common type of anti-inflammatory drugs used in veterinary medicine. These drugs are all familiar with the common names phenylbutazone (“bute”), aspirin, and Banamine (flunixin meglumine), just to name a few. These drugs work on the enzyme that changes inflammatory proteins into their active states. The enzyme that these drugs block is cyclooxygenase (COX) and the proteins that they inhibit are prostaglandin and thromboxanes. Both proteins are potent vasodilators. Recently, it has been discovered that there are two COX pathways in the production of prostaglandins, COX-1, and COX-2. COX-1 is primarily associated with normal physiological production of necessary prostaglandins while COX-2 is primarily associated with the inflammatory pathway. The prostaglandins produced via the COX-1 pathway are those that the horse needs to prevent gastric ulcers among others things. The older generation of NSAID works on both COX-1 and COX-2 pathways, so their use has a greater potential for unwanted side effects to occur. On the other hand, there are newer NSAID that have been developed to target just the COX-2 pathway. Examples are Rimadyl (carprofen) used in small animals, Vioxx (rofecoxib) and Celebrex (celecoxib), used in humans. There are currently no COX-2 drugs approved for the horse, although Rimadyl has been used in some cases. Studies are lacking on the current dosage, and safety and the drug is fairly expensive for regular equine use. There is also another NSAID that has been developed to be applied topically. Surpass (1% diclofenac sodium) topical cream is indicated for the control of pain and inflammation associated with osteoarthritis (OA) of the hock, knee, fetlock and pastern joints in horses. This cream is applied directly over the joint to help control inflammation. As an adjunct to a pain-management protocol, it is proven to be safe and effective when administered properly. When used off-label on soft tissue areas, very good results have been seen. Some problems of NSAID are the potential for gastric and colonic ulcers and kidney damage. NSAID are used in all types of injuries of the musclo-skeletal system and are used in conjunction with hydrotherapy and at times, DMSO.
The most potent anti-inflammatory drugs used in veterinary medicine are corticosteroids. These drugs inhibit enzyme production in all phases of the inflammatory process. These very potent drugs have a few serious drawbacks. They are so potent that it is been found that their use during an infectious process will inhibit the body’s own ability to fight off the infection, further risking the animal to succumb to the infectious process. Steroids have also been implicated in the origin of laminitis in horses when given in high doses. Judicious use of steroid has true benefits and can minimize the untoward effects of the inflammatory process. Steroids are used in all injuries of the musculo-skelatal system, especially in the joints of horses with OA and at times in combination with DMSO.
Two other drugs used extensively in the relief of OA in horse that have anti-inflammatory characteristics are hyaluronic acid (HA) and polysulfated glycosaminoglycans (PSGAG). HA is a naturally occurring protein that is associated with the synovial membrane and fluid in the joint. It decreases the movement of white blood cells into the inflamed site and decreases enzyme activities that are associated with inflammation. HA is formulated to be administered within the joint or intravenously. PSGAG are a group of sugar molecules that are the basic building blocks for HA. PSGAG actually stimulates the synthesis of hyaluronic acid in the horse. PSGAG inhibit the effects of various enzyme activities that cause inflammation. The primary route of administration is through intramuscular injections and oral supplementation.
This list is not an inclusive list of anti-inflammatory agents used, but the majority that are in clinical use at Equine Medical Service. These drugs and modalities can be used alone or in combination depending, on the severity of the damage done by the injury, the amount of inflammation present and the cause of the injury.