Ligament injuries are very common, and they typically afflict the younger population. Ligaments in the knee and foot for instance, withstand forces of up to five times body weight which occur in each of the 1.2 million steps a person takes each year.^{153, 154} While ligaments are notoriously slow healers, the repair and regeneration of the ligaments starts at 48 to 72 hours. Most ligament growth occurs between the third and sixth week after injury. One study found the maximum level of collagen in the ligament itself at six weeks.¹⁵⁵ Even though ligaments heal for a full year after injury, often the strength of the ligament after injury is only 50 to 70% of the original.¹⁵⁶ Other studies found ligaments regained only 30% of normal strength after severe injuries.^157-159

LIGAMENT INJURY AND THE SYMPATHETIC NERVOUS SYSTEM

Ligaments have long been thought of as inert structures whose primary function is to provide stability to a joint. What has not been so appreciated is the sequelae when ligaments are injured, not just on the joint, but on the sympathetic nervous system. Non-healed ligament injuries sensitize their own nociceptors to motion. Recall that nociceptors are specialized sensory neurons (nerve cells) that respond to tissue damage. The detection of noxious chemical, thermal, and mechanical stimuli are mediated by receptors on these cells.¹⁶⁰ There is a high density of both myelinated and unmyelinated nociceptors in the ligaments throughout the body.^161-164 These nociceptor sympathetic nerve fibers in injured ligaments elicit pain when the ligament is under too much tension. The density and distribution of these nociceptors, also known as substance-P nerve fibers, within the ligaments is significantly affected by injury, as well as the time since injury.^{165, 166} Damage done to ligaments may not initially result in a lot of pain, but the damage done to them, along with the degree of irritation on the surrounding nerve endings, may alter the firing pattern from these nerve endings in such a manner so as to cause increased activation of the sympathetic nervous system causing referral pains up and down the extremity.¹⁶⁷ (See Figure 12.) Referral pain patterns from injured ligaments is a well established phenomenon.^168-171 Ligament and other soft tissue injuries have been shown to cause regional and segmental variations in sympathetic activity including cutaneous sudomotor and vasomotor manifestations.

Figure 12. The non-healed ligament injury/CRPS connection. The poor healing of soft tissues, such as ligaments from immobilization, can sensitize nociceptors which ultimately can lead to CRPS.

These can include coldness and clamminess of the skin.^{172, 173} For instance, when hypertonic saline (6% NaCl) is injected into the interspinous ligaments or the periosteum of the spinous processes, the local transient pain was soon followed by a crescendo of deep pain in areas often remote from the site of injection, followed by autonomic nervous system changes in the referral pain sites. The condition whereby a hyperirritable spot (myofascial trigger point) causes referral pain from that location and autonomic phenomena is known as myofascial syndrome. The authors noted that “visceral, circulatory and thermoregulatory functions, controlled by the autonomic nervous system are continually coupled, in highly organized patterns, to musculoskeletal activity and changes in posture.” They go on to say, “In these stressful and, in some cases, painful experimental situations affecting small parts of the musculoskeletal system, the afferent volleys of impulses entering through individual dorsal roots appear to have become so prepotent as to dominate that part (i.e., corresponding and neighboring segments) of the sympathetic nervous system, and to take precedence over vertically organized patterns they ordinarily serve, and even to disrupt them. They do not, therefore, meet any particular functional demand, they are not adaptive and, in many cases, they persist after the provoking insult has ended. The autonomic concomitants of local myofascial irritation, injury, stress or pathology have not received widespread recognition in clinical practice…Whether reflexly or directly provoked, the hyperactivity of isolated portions of the sympathetic outflow serves no obvious adaptive function.”^{174, 175} In summary, these authors found that even a small irritation of the musculoskeletal system can cause such an enormous stimulation of the sympathetic nervous system (SNS) that the pain and overstimulation of the SNS overtakes everything and it serves no useful function.