Classically, TOS has been attributed to anomalous cervical ribs, muscles,  fractured clavicles or scar that passes through the nerve bundles squeezing them.

Another important cause for TOS is automobile accidents producing severe stretching or direct compressive trauma of the brachial plexus. Currently, at least in my practice, the overwhelming majority of cases are caused by repetitive work injury due to keyboard use. Characteristically, symptoms appear after an especially intense period of keyboard use due to various time pressures and, since they are initially mild in nature and disappear with rest, are easy to discount or ignore. However, after this initial appearance of symptoms, repetitive or forceful movements at work or normal activities of daily life cause these symptoms to reappear and worsen. Rest produces less relief, and stressful activities bring about pain more quickly and to a more intense degree.

On the one hand, direct injury to the nerves above the collarbone, such as in automobile accidents or fractures, seems to intuitively explain why there is pain. On the other hand, because it is more difficult to understand why light movements with the arms extended (such as when using a keyboard) would cause pain, many physicians discount these activities as causal.

My initial experience with this disorder also caused me a great deal of puzzlement until I began helping a surgeon during his thoracic-outlet dissections. It then became apparent that, in the vast majority of cases, the offending agents that kept these large nerve trunks irritated were coming from inside these nerves and that the surrounding tissues were only secondary, not primary, to the creation and worsening of symptoms. These agents produced scar like adhesions on the surface of the nerve covering, which (when examined under the microscope and with specific immune staining) revealed the presence of pain-causing nerves in these same fibrotic tissues. Once these tissues were removed, the abnormalities in the nerve dramatically decreased.
Barring frank trauma, the primary cause for symptoms and dysfunction is, thus, a localized irritation of the brachial plexus with secondary sources of inflammation (fibrous bands or bulked, edematous, or transformed muscles) promoting a vicious cycle. This inflammation is unusual in that it does not respond to arachidonic cascade inhibitors, such as nonsteroidal anti-inflammatories or corticosteroids, and is largely cell-mediated in nature. This concatenation of observations emphasizes the importance and involvement of immune and supportive (glial) cells, which have been largely overlooked in generating these painful symptoms, swelling, adhesions, and concomitant disability.

Over the last decade, white blood cells, Schwann cells in the periphery, and microglia centrally have been implicated in the development of chronic pain through their reactivity and secretion of neuropeptides and cytokines, some of which I have documented as being present in the adhesions investigated intraoperatively, as mentioned above. These molecules are part of tight, intermeshed networks that control local inflammation and pain, and can be destructive. Their presence and continued secretion in response to minimal stressors brings about a vicious cycle of immune-cell activation, swelling, fibrosis, and various pains and abnormal sensations.
Interestingly, this is not the only disorder in which this sequence of events occurs. Asthma, chronic regional pain syndrome, irritable bowel syndrome, possibly multiple sclerosis (as well as a number of others) are all initiated and maintained by this cascade of abnormal nerve reactivity and inflammation (neurogenic inflammation). In all of these, one finds abnormally reactive nerves, glia, mast cells, macrophages, and activated white blood cells perpetuating a dysfunctional vicious cycle.

What actually happens in the neurons themselves to cause this activation remains puzzling, but current favorite explanations include up-regulation of SNS-2Na voltage-related receptors and the K-Cl transporter KCC2 as underlying mechanisms.

In summary, whether the pain, abnormal sensation, and dysfunction are actually caused by direct trauma or microinjury engendered in repetitive work environments, the central fact of localized inflammation of the nerve, followed by extravasation, fibrosis, and the consequent ingrowth of inflammation-secreting nerves into these adhesive strands, is the central and perpetuating cause for the continued pain and disability, which in turn impinges on all of the adjacent structures in the area above the collarbone, often making them contributory, but secondary, actors in this drama. For more detailed information go to my article "Thoracic Outlet Syndrome as A Disorder of Neurogenic Inflammation".