Despite substantial clinical evidence and established criteria for the diagnosis of fibromyalgia (FM) we are still puzzled by the mechanisms underlying this debilitating condition. FM is a clinical syndrome characterized by chronic widespread pain and commonly associated with autonomic dysfunction. Numerous clinical investigations showed that patients with FM had a low threshold to pain, experienced a longer duration and a larger area of referral of experimentally induced pain. This suggests a state of disordered sensory processing in FM. Numerous clinical and experimental observations suggest that abnormal synthesis of the nerve growth factor (NGF) could be responsible for the development of hyperalgesia and autonomic dysfunction in different painful posttraumatic or inflammatory disorders. It was suggested that increased concentration of NGF in cerebrospinal fluid of patients with FM might be among the mechanisms involved in its development (Giovengo et al 1999). Spinal cord injury (SCI) associated with increased levels of NGF protein stimulates small-diameter primary afferent fibers sprouting. These afferent fibers contain calcitonin gene-related peptide and their arbors in the dorsal horn were significantly increased after SCI. This coincided with the development of autonomic dysfunction in these animals (Krenz et al 1999). Moreover, we have shown that concurrent with the development of autonomic dysfunction there was a widespread increase in responsiveness of spinal interneurons to the visceral or somatic pain stimulation in these animals (Krassioukov et al 2002). These fibers are unmyelinated afferent C-fibers and lightly myelinated afferent A delta fibers. Moreover, extent of small-diameter afferent sprouting after SCI correlated significantly with the magnitude of autonomic dysfunction. The aberrant sprouting and inappropriate synaptic connections within the spinal cord are probably responsible for the hyperresponsiveness of spinal circuits and widespread pain. Blocking intraspinal NGF with neutralizing antibody prevented not only sprouting of these fibers but also ameliorated autonomic dysfunction in animals with experimental SCI. Our experimental data from animals with SCI provide insight into the pathophysiology of widespread pain, allodynia, and autonomic dysfunction that could be partially involved in the development of these conditions in patients with FM.

National Fibromyalgia Research Association
Neurology and New Treatment Modalities in Fibromyalgia
Symposium - Portland, Oregon – October 2002