MECHANISM OF PAIN IN PATIENTS WITH FIBROMYALGIA SYNDROME
Principal Investigator: ROLAND M STAUD
Abstract: DESCRIPTION: Fibromyalgia syndrome (FMS) is a symptom based diagnosis that depends on the presence of chronic widespread pain and decreased mechanical pain threshold at >= 11 well defined tender points. FMS shows wide overlap with other pain syndromes, including chronic fatigue syndrome and irritable bowel syndrome. All these disorders share chronic, unexplained pain as a clinically relevant symptom and several or all of these syndromes often coexist in an individual patient. Therefore, discovery of FMS pain mechanisms may also benefit patients with related pain syndromes. We have recently shown that FMS patients demonstrate abnormal pain processing, including excessive temporal summation of second pain (windup) and central sensitization. With this application, we will expand our detailed investigation of central/peripheral pain mechanism relevant to FMS pain, using forms of repetitive stimulation that reliably evoke perceptions of second pain. Second pain results from impulse conduction in peripheral C (unmyelinated) afferent axons, and temporal summation of second pain has been shown to result from a central NMDA receptor mechanism within the dorsal horn. The proposed experiments will evaluate peripheral influences on FMS pain and abnormal temporal summation of experimental pain, will describe the central patterns of NMDA receptor activation by nociceptive input, and will compare effects of NMDA antagonists on clinical and experimental pain of female FMS patients and male and female control subjects. Aim 1 will focus on the relationship of clinical pain to abnormal windup (WU) in FMS. Since clinical pain intensities reported for different body areas seem to vary widely within and between FMS patients, we will first test the magnitude of WU and clinical pain ratings in all four body quadrants of FMS patients and then statistically determine the strength of their association. Repetitive thermal and mechanical stimuli will be delivered to FMS patients and normal controls (NC). If clinical pain is indeed related to C-afferent mediated mechanisms we expect to find a positive correlation between WU measurements and clinical pain. Using exercise bouts or ischemic muscle compressions alternating with rest periods, we will characterize the role of musculoskeletal nociceptor input on a) local and generalized pain and b) WU abnormalities of FMS patients (Aim2). We expect to find that muscular activity and associated receptor stimulation will enhance clinical pain both locally and generally. We will test the effects of NMDA receptor antagonists on clinical pain, first pain, second pain, and WU (Aim 3). We will compare the psychophysical test results across pain-free NC and FMS patients in order to ascertain the extent to which abnormalities of NMDA mechanisms contribute to FMS pain with a special focus on FMS related differences. We will use functional brain imaging (fMRI) of temporal summation of second pain in NC and FMS patients to characterize the encoding of brief, repetitive, thermal stimuli in cortical and subcortical structures (Aim 4). We posit that the enhanced WU of FMS patients will strongly correlate with greater neural activation as compared to NC. The proposed experiments will answer important questions about peripheral/central mechanisms of chronic pain that are relevant to the diagnosis and treatment of FMS. In addition, our findings may contribute to the understanding of pain mechanisms related to other chronic pain disorders.
Funding Period: 1999-06-10 - 2010-02-28
more information: NIH RePORT
- Overall fibromyalgia pain is predicted by ratings of local pain and pain-related negative affect--possible role of peripheral tissuesR Staud
Department of Medicine, University of Florida, College of Medicine Gainesville, FL 32610 0221, USA
Rheumatology (Oxford) 45:1409-15. 2006..We hypothesized that the overall clinical pain is largely determined by the pain intensity of local body areas. Thus, we assessed the role of local body pains as predictors of overall clinical pain in FM patients...
- Cutaneous C-fiber pain abnormalities of fibromyalgia patients are specifically related to temporal summationRoland Staud
Department of Medicine, University of Florida College of Medicine, Gainesville, FL 32610 0221, USA
Pain 139:315-23. 2008..These findings provide strong support for alterations of central pain sensitivity and not peripheral sensitization or rating bias as responsible for TSSP differences between NC and FM subjects...
- Long-term trials of pregabalin and duloxetine for fibromyalgia symptoms: how study designs can affect placebo factorsRoland Staud
Pain 136:232-4. 2008
- Abnormal pain modulation in patients with spatially distributed chronic pain: fibromyalgiaRoland Staud
Department of Medicine, University of Florida College of Medicine, Gainesville, FL 32610 0221, USA
Rheum Dis Clin North Am 35:263-74. 2009..Long-term prospective studies that could yield insight into the role of heightened pain sensitivity and pain disinhibition for the development of chronic pain disorders like fibromyalgia in the general population are lacking, however...
- Enhanced central pain processing of fibromyalgia patients is maintained by muscle afferent input: a randomized, double-blind, placebo-controlled studyRoland Staud
Department of Medicine, University of Florida, Gainesville, FL 32610, USA
Pain 145:96-104. 2009..02). Neither lidocaine nor saline injections significantly affected clinical FM pain ratings, a result most likely due to the very low dose of lidocaine (50mg) used in this trial...
- Pharmacological treatment of fibromyalgia syndrome: new developmentsRoland Staud
Department of Medicine, University of Florida, College of Medicine, Gainesville, Florida 32610 0221, USA
Drugs 70:1-14. 2010..However, new pharmacological approaches for the treatment of fibromyalgia pain and insomnia using sodium oxybate appear to be promising...
- Do past pain events systematically impact pain ratings of healthy subjects or fibromyalgia patients?Roland Staud
Department of Medicine, University of Florida, Gainesville, FL 32610 0221, USA
J Pain 11:142-8. 2010..These results do not provide support for the strong assertion that pain rating scales are elastic, ie, being used differently depending on the severity of past pain events such as childbirth...
- Pain variability in fibromyalgia is related to activity and rest: role of peripheral tissue impulse inputRoland Staud
Department of Medicine, University of Florida, Gainesville, Florida, USA
J Pain 11:1376-83. 2010..Additionally, FM subjects' pain sensitivity to mechanical pressure decreased after each exercise and rest session...
- Two novel mutations of SCN9A (Nav1.7) are associated with partial congenital insensitivity to painRoland Staud
Department of Medicine, University of Florida, Gainesville, FL 32610, United States
Eur J Pain 15:223-30. 2011..The ability to sense at least some danger signals may be advantageous and ameliorate the otherwise increased morbidity and mortality of some individuals with congenital insensitivity to pain...
- Brain activity associated with slow temporal summation of C-fiber evoked pain in fibromyalgia patients and healthy controlsRoland Staud
Department of Medicine, McKnight Brain Institute, University of Florida, Gainesville, FL 32610, United States
Eur J Pain 12:1078-89. 2008..These results suggest that enhanced neural mechanisms of TSSP in FM are reflected at all pain related brain areas, including posterior thalamus, and are not the result of selective enhancement at cortical levels...
- Advanced continuous-contact heat pulse design for efficient temporal summation of second pain (windup)Roland Staud
Department of Medicine, University of Florida College of Medicine, Gainesville, FL 32610, USA
J Pain 7:575-82. 2006..Thus, specifically designed continuous-contact heat pulses can be used to elicit distinct second pain and robust WU(SP), thereby providing an efficient psychophysical test of this phenomenon...
- Biology and therapy of fibromyalgia: pain in fibromyalgia syndromeRoland Staud
Division of Rheumatology and Clinical Immunology, McKnight Brain Institute, University of Florida, Gainesville, Florida 32610, USA
Arthritis Res Ther 8:208. 2006..Better understanding of these mechanisms and their relationship to central sensitization and clinical pain will provide new approaches for the prevention and treatment of FM and other chronic pain syndromes...
- Brain activity related to temporal summation of C-fiber evoked painRoland Staud
Department of Medicine, McKnight Brain Institute, University of Florida, Gainesville, FL 32610, USA
Pain 129:130-42. 2007....
- Spatial summation of mechanically evoked muscle pain and painful aftersensations in normal subjects and fibromyalgia patientsRoland Staud
Department of Medicine, University of Florida, College of Medicine, Gainesville, FL 32610 0221, USA
Pain 130:177-87. 2007..The important role of MSSP for pain encoding suggests that decreasing pain in some muscle areas by local anesthetics or other means may improve overall clinical pain of FM patients...
- Temporal summation of second pain and its maintenance are useful for characterizing widespread central sensitization of fibromyalgia patientsRoland Staud
Department of Medicine, University of Florida, Gainesville, Florida 32610 0221, USA
J Pain 8:893-901. 2007..These findings demonstrate that central sensitization of FM patients is widespread and similar along the spinal neuroaxis...
- Treatment of fibromyalgia and its symptomsRoland Staud
University of Florida College of Medicine, Department of Medicine, Division of Rheumatology and Clinical Immunology, McKnight Brain Institute, Gainesville, FL 32610 0221, USA
Expert Opin Pharmacother 8:1629-42. 2007..Based on this evidence, a stepwise program emphasizing education, medications, exercise and cognitive therapy can be recommended...
- Characteristics of electronic visual analogue and numerical scales for ratings of experimental pain in healthy subjects and fibromyalgia patientsDonald D Price
Department of Neuroscience, University of Florida, College of Medicine, Gainesville, FL 32610 0221, USA
Pain 140:158-66. 2008..Finally, all three groups (total of 55 subjects) found the scales easy to use after brief instructions, though subjects strongly preferred the use of VAS-N or VAS in comparison to NUM scale...
- Effective connectivity among brain regions associated with slow temporal summation of C-fiber-evoked pain in fibromyalgia patients and healthy controlsJason G Craggs
Department of Clinical and Health Psychology, University of Florida, Gainesville, FL 32610, USA
J Pain 13:390-400. 2012..These results provide evidence for significant overlap of the fundamental brain mechanisms that process sensory and affective information related to TSSP in NC and FM groups...