Neuropeptides CRH, SP, HK-1, and Inflammatory Cytokines IL-6 and TNF Are Increased in Serum of Patients with Fibromyalgia Syndrome, Implicating Mast Cells.

Fibromyalgia syndrome (FMS) is a chronic, idiopathic condition of widespread musculoskeletal pain affecting more women than men. Even though clinical studies have provided evidence of altered central pain pathways, the lack of definitive pathogenesis or reliable objective markers has hampered development of effective treatments. Here we report that the neuropeptides corticotropin-releasing hormone (CRH), substance P (SP), and SP-structurally-related hemokinin-1 (HK-1) were significantly (P = 0.026, P < 0.0001, and P = 0.002, respectively) elevated (0.82 ± 0.57 ng/ml, 0.39 ± 0.18 ng/ml, and 7.98 ± 3.12 ng/ml, respectively) in the serum of patients with FMS compared with healthy controls (0.49 ± 0.26 ng/ml, 0.12 ± 0.1 ng/ml, and 5.71 ± 1.08 ng/ml, respectively). Moreover, SP and HK-1 levels were positively correlated (Pearson r = 0.45, P = 0.002) in FMS. The serum concentrations of the inflammatory cytokines interleukin (IL)-6 and tumor necrosis factor (TNF) were also significantly (P = 0.029 and P = 0.006, respectively) higher (2.97 ± 2.35 pg/ml and 0.92 ± 0.31 pg/ml, respectively) in the FMS group compared with healthy subjects (1.79 ± 0.62 pg/ml and 0.69 ± 0.16 pg/ml, respectively). In contrast, serum IL-31 and IL-33 levels were significantly lower (P = 0.0001 and P = 0.044, respectively) in the FMS patients (849.5 ± 1005 pg/ml and 923.2 ± 1284 pg/ml, respectively) in comparison with healthy controls (1281 ± 806.4 pg/ml and 3149 ± 4073 pg/ml, respectively). FMS serum levels of neurotensin were not different from controls. We had previously shown that CRH and SP stimulate IL-6 and TNF release from mast cells (MCs). Our current results indicate that neuropeptides could stimulate MCs to secrete inflammatory cytokines that contribute importantly to the symptoms of FMS. Treatment directed at preventing the secretion or antagonizing these elevated neuroimmune markers, both centrally and peripherally, may prove to be useful in the management of FMS.

An Online Survey of Patients' Experiences Since the Rescheduling of Hydrocodone: The First 100 Days.

OBJECTIVE: To conduct an Internet patient survey through the National Fibromyalgia & Chronic Pain Association on reactions to the first 100 days following the rescheduling of hydrocodone. METHODS: Face-valid survey questions were created with expert consensus along with repurposed questions used on previous NFMCPA surveys covering domains such as demographics and symptoms. The questionnaire was designed to be administered over the Internet. RESULTS: 6,420 responders met screening criteria and completed the survey. Most (5,181, or 82.5%) had been prescribed hydrocodone for more than 1 year. 2,296, (39.0%) reported no changes in access to hydrocodone, while the majority experienced some barriers. Of those who could no longer get hydrocodone, 1,067 (18.1%) borrowed pain medications, 1,007 (17.1%) turned to marijuana, 773 (13.1%) used alcohol, and 135 (2.3%) used illicit drugs. Most respondents had to visit their healthcare providers more often (N = 3,699, 64.2%) and 1,735 (30.3%) reported some type of issue interacting with their pharmacy. Most felt that the rescheduling was neither a fair nor appropriate solution to the abuse of hydrocodone (N = 4,938, 88.3%). For those still working, 801 (46.2%) reported that they had missed work because of the stricter regulations. 1,462 (27.2%) reported having thoughts of suicide since the rescheduling. SIGNIFICANCE: The unintended consequences for people with chronic pain that have been caused by the rescheduling effort to impede hydrocodone abuse are negatively impacting thousands. These consequences include suffering from being placed on less effective drugs, increased cost, inconvenience, and negative influence on physician-patient and pharmacist-patient relationships.

Fibromyalgia syndrome in need of effective treatments.

Fibromyalgia syndrome (FMS) is a chronic, idiopathic condition of widespread musculoskeletal pain, affecting primarily women. It is clinically characterized by chronic, nonarticular pain and a heightened response to pressure along with sleep disturbances, fatigue, bowel and bladder abnormalities, and cognitive dysfunction. The diagnostic criteria have changed repeatedly, and there is neither a definitive pathogenesis nor reliable diagnostic or prognostic biomarkers. Clinical and laboratory studies have provided evidence of altered central pain pathways. Recent evidence suggests the involvement of neuroinflammation with stress peptides triggering the release of neurosenzitizing mediators. The management of FMS requires a multidimensional approach including patient education, behavioral therapy, exercise, and pain management. Here we review recent data on the pathogenesis and propose new directions for research and treatment.