Fibromyalgia Syndrome: New Developments in Pathophysiology and Management

CNS Spectrums ◽  
2008 ◽  
Vol 13 (S5) ◽  
pp. 4-5 ◽  
Author(s):  
I. Jon Russell

Fibromyalgia syndrome (FMS) is a common, chronically painful condition that is still seeking a home among the clinical professions. It is characterized by moderately severe soft-tissue pain and allodynia, which suggests a role for one group of specialists, but its pathogenesis is in the nociceptive machinery of the central nervous system, which defines the territory of other specialties. Comorbidities such as insomnia, cognitive dysfunction, depression, anxiety, recurrent headaches, dizziness, fatigue, morning stiffness, dysesthesia, irritable bowel syndrome, and irritable urethra logically invoke input from practitioners from almost every field of medicine.The precipitating causes of FMS may vary among individuals, but a mechanism underlying the painful symptoms involves central sensitization leading to an amplified perception of pain. As a result, this condition is recognized as the human model for chronic widespread allodynia. Biological abnormalities that are detected in most patients by objective methods include dysfunctional sleep (polysomnography), central sensitization (functional magnetic resonance imaging), temporal summation (windup, second pain), and facilitation of nociception (elevated spinal fluid levels of substance P, deficient biogenic amines that fail to maintain descending inhibition, and, in primary FMS, elevated spinal fluid levels of nerve growth factor).Treatment of FMS is symptomatic and multimodal, including education, physical modalities, and medications that target central neural pathways. Rehabilitation goals include improved physical function, social adaptation, emotional balance, and a better quality of life. Several series of placebo-controlled clinical trials have made available new medications with unique therapeutic mechanisms. Thus, it can be predicted that the next 10 years will see validation of a clinical case definition, more interest in the underlying pathogenesis, a better understanding of how medical care should be adapted to subgroup variations, new medications with specific domain indications, mechanism-directed polypharmacy, characterization of the genetic predisposition, and more emphasis on preventable inciting events.

1999 ◽  
Vol 271 (3) ◽  
pp. 183-186 ◽  
Author(s):  
C Mattei ◽  
J Molgó ◽  
X Joseph ◽  
M Israël ◽  
C Bloy

1994 ◽  
Vol 37 (11) ◽  
pp. 1593-1601 ◽  
Author(s):  
I. Jon Russell ◽  
Malcolm D. Orr ◽  
Bruce Littman ◽  
Gilbert A. Vipraio ◽  
David Alboukrek ◽  
...  

2021 ◽  
Vol 126 (3) ◽  
pp. 946-956
Author(s):  
Roland Staud ◽  
Jeff Boissoneault ◽  
Song Lai ◽  
Marlin S. Mejia ◽  
Riddhi Ramanlal ◽  
...  

“Windup” and its behavioral correlate “temporal-summation-of-second pain” (TSSP) represent spinal cord mechanisms of pain augmentation associated with central sensitization and chronic pain. Fibromyalgia (FM) is a chronic pain disorder, where abnormal TSSP has been demonstrated. We used fMRI to study spinal cord and brainstem activation during TSSP. We characterized the time course of spinal cord and brainstem BOLD activity during TSSP which showed abnormal brainstem activity in patients with FM, possibly due to deficient pain modulation.


2006 ◽  
Vol 28 (9) ◽  
pp. 473-478 ◽  
Author(s):  
S. R. SOUSA-PEREIRA ◽  
A. L. TEIXEIRA ◽  
L. C. S. SILVA ◽  
A. L. S. SOUZA ◽  
C. M. ANTUNES ◽  
...  

Pain ◽  
2001 ◽  
Vol 91 (1) ◽  
pp. 165-175 ◽  
Author(s):  
Roland Staud ◽  
Charles J. Vierck ◽  
Richard L. Cannon ◽  
Andre P. Mauderli ◽  
Donald D. Price

2015 ◽  
Vol 8 (1) ◽  
pp. 51-51
Author(s):  
A. Jonsson ◽  
A.-L. Lind ◽  
M. Hallberg ◽  
F. Nyberg ◽  
T. Gordh

Abstract Aims Neuropathic pain is a complex and painful condition, which is difficult to treat and causes a lot of suffering. The substance P (SP) system is well known to be involved in nociceptive signaling and it has previously been shown that the cerebrospinal fluid (CSF) level of SP is decreased in neuropathic pain. In this study we analyzed CSF from chronic neuropathic pain patients for the levels of SP1–7, an N-terminal fragment of SP with the ability to alleviate thermal as well as mechanical hypersensitivity in different animal models of chronic neuropathic pain, e.g. [1,2]. Methods CSF was collected from 11 neuropathic pain patients, treated with SCS, who had refrained from using their spinal cord stimulator for 48h. Control CSF was collected from 11 patients without any known neurological disorder, who underwent minor surgery under spinal anesthesia. The CSF samples were analyzed for the levels of SP1–7 using radioimmunoassay. Results The results revealed a decrease in the level of SP1–7 compared to controls. We believe that the lower level ofSP1–7 most likely is a consequence of reduced amount of its precursor SP in the neuropathic pain patients. Conclusions Our results indicate that the SP system is changed in patients with neuropathic pain and that SP-related peptides, including SP1–7, might serve as biological markers for the patho-physiology of chronic neuropathic pain.


1999 ◽  
Vol 81 (3) ◽  
pp. 1095-1103 ◽  
Author(s):  
Qing Lin ◽  
Jing Wu ◽  
Yuan Bo Peng ◽  
Minglei Cui ◽  
William D. Willis

Inhibition of primate spinothalamic tract neurons by spinal glycine and GABA is modulated by guanosine 3′,5′-cyclic monophosphate. Our recent work has suggested that the nitric oxide/guanosine 3′,5′-cyclic monophosphate (NO/cGMP) signal transduction system contributes to central sensitization of spinothalamic tract (STT) neurons in part by influencing the descending inhibition of nociception resulting from stimulation in the periaqueductal gray. This study was designed to examine further whether activation of the NO/cGMP cascade reduces the inhibition of the activity of STT neurons mediated by spinal inhibitory amino acid (IAA) receptors. Responses of STT cells to noxious cutaneous stimuli were inhibited by iontophoresis of glycine and GABA agonists in anesthetized monkeys. Administration of 8-bromoguanosine-3′,5′-cyclophosphate sodium (8-bromo-cGMP), a membrane permeable analogue of cGMP, either by microdialysis or by iontophoresis reduced significantly the IAA-induced inhibition of wide dynamic range (WDR) STT cells in the deep layers of the dorsal horn. The reduction in inhibition lasted for up to 1–1.5 h after the cessation of drug infusion. In contrast, IAA-induced inhibition of WDR STT cells in the superficial dorsal horn and high-threshold (HT) cells in superficial or deep layers was not significantly changed during 8-bromo-cGMP infusion. Iontophoresis of 8-bromo-cGMP onto STT cells produced the same actions as produced by microdialysis of this agent, but the effect was not as long-lasting nor as potent. Finally, an attenuation of the IAA receptor–mediated inhibition of STT cells produced by iontophoretic release of a NO donor, 3-morpholinosydnonimine, could be blocked by pretreatment of the spinal cord with a guanylate cyclase inhibitor, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one. These results suggest that an increased spinal cGMP level contributes to the sensitization of WDR STT neurons in the deep dorsal horn in part by down-regulating spinal IAA receptors. However, no evidence is provided in this study that the NO/cGMP cascade regulates IAA receptors on HT and superficial WDR neurons. Combined with the preceding studies, our data support the view that NO and cGMP function in the same signal transduction cascade and play an important role in central sensitization.


2004 ◽  
Vol 101 (6) ◽  
pp. 1400-1408 ◽  
Author(s):  
Hanne Gottrup ◽  
Gitte Juhl ◽  
Anders D. Kristensen ◽  
Robert Lai ◽  
Boris A. Chizh ◽  
...  

Background In chronic pain, increased activity from intact or damaged peripheral nerve endings results in an enhanced response in central pain transmission systems, a mechanism known as central sensitization. Central sensitization can also be invoked in human experimental models. Therefore, these models may be useful to characterize novel analgesics in humans. The anticonvulsant gabapentin has demonstrated efficacy in patients with neuropathic pain, but its mode of action remains unclear. This study examined the effects of gabapentin on signs of central sensitization (brush and pinprick hyperalgesia) in a human model of capsaicin-evoked pain, using a gabapentin dosing regimen similar to that used in the clinic. The aims were to determine whether gabapentin, dosed in a manner similar to that used in the clinic, affected the various components of central sensitization and to assess the utility of this model for characterizing novel analgesics. Methods Intradermal capsaicin (100 microg/20 microl) was administered in the volar forearm of 41 male human volunteers to induce pain and clinical signs of central sensitization. Gabapentin (titrated to 2,400 mg daily) or placebo was given orally for 15 days in a randomized, double-blind, parallel-group design. The capsaicin test was conducted at baseline and after gabapentin or placebo. Endpoints were the size of areas of brush-evoked allodynia (with cotton gauze) and pinprick hyperalgesia (with von Frey filament), and the intensity of ongoing brush- and pinprick-evoked pain. Results Gabapentin significantly reduced the area of brush allodynia compared with placebo (P </= 0.05) and insignificantly attenuated the area of pinprick hyperalgesia. Gabapentin had no significant effect on spontaneous and evoked pain intensity. Conclusion Oral gabapentin, administered to healthy volunteers in a regimen similar to that used in treating chronic neuropathic pain, reduces measures of central sensitization evoked by intradermal capsaicin. This suggests that the pain-relieving effect in chronic neuropathic pain condition is linked to the effect of gabapentin on central sensitization. The ability of the capsaicin model to detect the efficacy of this standard treatment of neuropathic pain suggests that it may have a predictive value for detection of efficacy in human subjects.


2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Kathryn A. Thibert ◽  
Gerald V. Raymond ◽  
Jakub Tolar ◽  
Weston P. Miller ◽  
Paul J. Orchard ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document