ABSTRACT
This paper proposes a possible etiology for the increased levels of substance P in the cerebrospinal fluid of fibromyalgia patients. Inadequate regulation of gene transcription by thyroid hormone is the most plausible explanation. Thyroid hormone regulates substance P in discrete nuclei of the brain, in the anterior pituitary, in the lumbar spinal cord, and in the dorsal root ganglia. Most significantly, however, thyroid hormone directly regulates transcription of the preprotachykinin gene, which codes for preprotachyki-nin-A (the precursor of substance P) and the substance P receptor. Studies confirm the negative regulation of substance P by thyroid hormone: increasing the availability of thyroid hormone decreases levels of substance P; decreasing thyroid hormone increases levels of substance P.
Inadequate regulation of gene transcription by thyroid hormone could not only account for high substance P levels, but for all other objective findings and associated symptoms in fibromyalgia. The fact that thyroid hormone negatively regulates substance P, coupled with the finding of a high incidence of hypothyroidism in fibromyalgia patients, should prompt investigation of the possible role of inadequate gene regulation by thyroid hormone in fibromyalgia patients with high substance P levels.