It is generally assumed that cryo-therapy causes small blood vessels on the body surface to constrict. This effect may help reduce hemorrhage and edema. Edema acts as a negative metabolic factor for cells surrounding the initial injury site because of the longer transport route for oxygen to reach the cells. Edema may cause capillary constriction due to increased extra cellular pressure.  Cold therapy may also slow hematoma formation due to decreased blood flow. Blood vessel constriction is a reflex mechanism aimed at minimizing the loss of heat by the body and is mediated by both the autonomic nervous system and local hormonal control.

Following initial vasoconstriction, vasodilation occurs. This appears to be a protective mechanism to maintain viability of body tissues at low temperatures. When tissue temperature falls below 18° C, the initial reduction in blood flow is followed by a compensatory increase in blood flow. This appears to be due to dilation of muscle blood vessels.  This vasodilatory response varies between different types of tissue and, in humans, appears to be greatest in areas subjected to frostbite.  Reflex vasodilation was not recognized after thirty minutes of cold therapy at 39.2° F .

Anti-inflammatory effects. It is also assumed that cold reduces the inflammatory response after soft tissue injuries by reducing pain and post-injury edema. It is believed that cold reduces inflammation by inhibiting histamine, neutrophil activation, collagenase activity and synovial leukocytes.1

Hypometabolism. The decrease in inflammatory response seen after the application of cold is enhanced due to decreased tissue metabolism, which limits secondary tissue damage due to hypoxia.  Some studies suggest that this hypometabolism is more important than the vascular response in limiting the extent of tissue injury.  For example, enzymatic activity in the knee joints of human patients with rheumatoid arthritis increases four times with an increase in temperature from a normal 33° C to 36° C. Studies have shown that metabolic enzyme activity is decreased by about 50 per cent when the temperature is lowered by 10° C.

Reduced muscle spasm. Cold decreases activity of the muscle spindle, which in turn decreases muscle spasticity.30 Cold also makes muscle tissue stiffer and results in changes in viscosity and plasticity of the various tissues. There seems to be a direct relationship between the cooling temperature and the muscle performance.2

Decreased nerve conduction velocity. Decreased nerve conduction velocity has been documented as a result of the application of cold. This is thought to contribute to the reported analgesic effects of cold (see below).

It is generally thought that cold decreases swelling, however, numerous studies have shown that application of cold actually increases subcutaneous edema. Greater swelling occurred in limbs following application of cold in both injured and uninjured limbs in an experimental model of ligament injury in pigs.   Increased swelling was shown with the application of cold for treatment of postacute ankle sprains in people.  Increased subcutaneous swelling may be due to the fact that cutaneous veins and arteries appear to react differently to cold, with veins staying constricted atlower temperatures.   Increased subcutaneous swelling following application of cold may also be due to increased permeability of superficial lymph vessels.  It should be noted that many clinical studies related to the use of cold in humans do not indicate increased swelling following the application of cold, perhaps because first aid combines cold with compression and elevation.

Cyrotherapy is proposed to help preserve the elastic properties of collagen in soft tissue injuries. Cooling results in enhanced stiffness and stability in injured tissue.  This effect could be potentially detrimental, however. Increased tissue stiffness and analgesic effects could conceivably make tissues less pliable and impede the normal protective mechanisms that pain provides, thus rendering the tissue more susceptible to injury during vigorous exercise. Tissue elasticity is critical to normal tendon function, for example, and anything that would increase tissue stiffness would presumably be contraindicated as it could conceivably predispose to injury.   The use of cryotherapy is considered contraindicated in humans prior to exercise because the increased collagen stiffness results in a decrease in muscle flexibility.

Cold has been frequently shown to have an analgesic effect. Clinical and experimental research on pain and pain threshold indicates that pain reduction occurs after the tissues are cooled to 10°C to 15°C; however the duration of pain relief is uncertain.  The mechanism for pain relief may include breaking the pain-spasm cycle or decreasing nerve conduction velocity. The decrease in nerve conduction velocity appears to be proportional to the decrease in tissue temperature rather than the changes in local circulation. Nerve conduction is continually slowed down when temperatures fall, until finally, nerve fibers cease conducting altogether. The application of cold also appears to act as a counter irritant producing a shower of nerve impulses that makes receptors momentarily refractory to pain impulses. Other proposed mechanisms for cold-induced pain relief include a decreased production of pain-producing substances locally,  interference with gate control pain mechanisms (cold might provide as strong sensory input which "closes the gate" and reduces the transmission of painful stimuli and release of endorphins with a resulting influence on opioid receptors in the central nervous system.

TIME OF APPLICATION  In the treatment of acute injuries, cryotherapy is best initiated as soon as possible after the onset of the injury. In studies on human ankle injuries, cryotherapy initiated on the day of injury (day 0) or on day 1 allowed for an earlier resumption of full activities that did cryotherapy begun on day two.

LENGTH OF APPLICATION  There appears to be a general consensus in human medicine that the optimum duration of cold therapy is from 20 to 30 minutes.  The effects of cold application are seen rather quickly. Investigators using triple-phase technetium-99m scintigraphs (bone scans) were able to show that the topical application of ice for 20 minutes decreased skeletal blood flow in the human knee by an average of 19.3% and soft tissue blood flow by 25.8%.  In another study that attempted to increase blood flow, cold packs were applied to human ankles for 25 minutes and the responses were measured using strain gauge plethysmography. That study found decreased blood flow during the 25 minutes of cold application and for 25 minutes after removal of the ice packs.  In another study, to produce a measurable, albeit small (5.1%) decrease in blood flow and metabolism in the deep tissues of a human knee joint, specifically the bones, only 5 minutes of ice application were necessary. A maximal response was produced within 25 minutes of icing, fourfold greater than that seen at 5 minutes. There was a mean increase in arterial blood flow at 10 minutes, suggesting a possible reflex vasodilation in the arterial blood vessels in response to cooling, with subsequent decreases again noted at 15, 20 and 25 minutes of cooling. 

Clinical studies from human medicine seem to agree that cryotherapy does improve recovery from injuries. It should be noted, however, that many of these studies combine cryotherapy with other therapies such as compression, limb elevation and analgesic therapy. Cold does reduce the temperature of the tissues to which it is applied. In addition, other physiologic processes, such as neuromuscular action, nerve conduction and plasticity of tissues are also affected by cold. It is not clear if it is important to cool injured temperatures to a point near freezing or if more moderate cooling methods are equally effective. Cold may also have negative effects. Increased swelling of the subcutaneous tissues may be seen after application of cold therapy. In experimental situations, cold can increase as well as decrease the inflammatory reaction. Excessive application of cold to tissue has the potential to cause tissue damage or nerve injury.