This double issue of the Journal of Musculoskeletal Pain is devoted to the proceedings of MYOPAIN 2007, the International Congress of the International MYOPAIN Society [IMS], held in Washington, DC, August 20–23, 2007. The Congress was particularly exciting this year, as important new insights in the fields of myofascial pain syndrome [MPS] and fibromyalgia syndrome [FMS] were reported. The papers in this issue of the Journal represent major advances in our understanding of these conditions and provide guidance to the further study of muscle pain. Central sensitization, peripheral sensitization, and genetic polymorphisms in muscle disease were central to many of the presentations in this Congress and represent a unifying theme in the understanding of these two syndromes.
Laurence Bradley presents data that supports a genetic contribution to the development of FMS and psychological distress in first-degree relatives of FMS patients. The gender distribution is striking, supporting previous studies showing a sex-linked effect. Most interesting are the possibilities that genetic polypmorphism is associated with FMS and that catechol-O-methyltransferase gene variants may play a role in the development and maintenance of FMS. Brian Cairns and Xudong Dong evaluate glutamate activation of N-methyl-d-aspartate receptors [NR] in myofascial temporomandibular disorders, a localized MPS. They report that elevated interstitial glutamate is found in certain noninflammatory muscle pain syndromes. Glutamate activation of peripheral excitatory amino acid receptors such as NR is likely to be a factor in the generation of muscle pain. Such activation is greater in females than in males, apparently due in part to estrogen-mediated enhancement of peripheral NR expression, providing one explanation for the sex-linked association in certain types of muscle pain that has long been noted. Daniel Clauw develops these ideas into a concept of FMS pathogenesis, showing how the genetic predisposition to FMS involves sensory processing and the development of central sensitization that is seen in FMS, but that is not unique to FMS. Dr. Clauw clearly details the changes in the central nervous system ascending and descending pain modulation systems seen in FMS and other chronic pain states. He then relates the changes in pain processing to potential treatments that might be used in managing FMS, taking us from the laboratory bench to the treatment room. He discusses the two important classes of drugs that are now creating excitement in the treatment of these chronic pain states, the mixed serotonin/norepinephrine reuptake inhibitors that enhance descending spinal inhibition of ascending pain impulses, and the alpha 2 delta ligands that decrease the release of excitatory neurotransmitters such as glutamate and neurokinins.
As important as central hypersensitization is in FMS, and most likely in MPS as well, peripheral nociceptive input remains a major factor in both conditions. Roland Staud describes the role of peripheral nociceptive input in FMS in the development of allodynia and hyperalgesia. He presents data to support the concept that abnormal muscle perfusion results in sensitization of intramuscular [peripheral] nociceptors that provide tonic impulse to central pathways leading to central sensitization. Fibromyalgia syndrome and MPS, so far as we know, are muscle pain states without traditional inflammatory changes within the muscle. Walder and Sluka present studies that demonstrate that the injection of acidic saline produces mechaninal hyperalgesia without peripheral tissue damage. Two injections of acidic saline 5 days apart result in activation of central mechanisms that produce bilateral hyperalgesia. The central responses that are activated include the cAMP pathway in the spinal cord, increases in cyclic AMP responsive element binding protein [CREB], excitatory glutamate receptors, and spinal neurons that transmit nociceptive information and rostral ventromedial medullary descending facilitation of pain transmission. Jay Shah focuses attention on the changes in the local milieu of the trigger point [TrP] that provides the basis for peripheral sensitization. Shah and his colleagues at the National Institutes of Health in Bethesda, Maryland, provide the first detailed description of biochemical, neuropeptide, and cytokine changes in the myofascial TrP region. Their real-time microdialysis data distinguishes the active from the latent TrP and from normal muscle and show that the concentrations of these substances change abruptly following a local twitch response in the active TrP. The rapid decrease toward normal correlates well with the clinical observation of rapid pain reduction after local twitch response is elicited in treatment situations. It is also most interesting that Shah and associates have found that the active TrP point milieu is acidic, to pH 4, given the work from Sluka's lab, reported here, that shows that acidic saline injections can produce pain and activate central sensitization and hyperalgesia without inflammation.
Several speakers address the evaluation of muscle pain syndromes. Thomas Graven-Nielsen and Lars Arendt-Nielsen present a detailed critique of psychosocial assessment of muscle pain. The methodology they present outlines reliable methods for quantitative assessment of muscle hyperalgesia, providing insight into the peripheral and central mechanisms of pain and into the functional adaptations made in response to muscle pain. Philip Mease delves deeply into the rapidly expanding field of outcome assessment of FMS and describes the usefulness and validity of many of the instruments available today. His highly critical analysis is of great value to the clinician and researcher alike.
Harvey Moldofsky, with his colleagues, first brought the relationship of sleep disturbance and the development of pain to the attention of the medical community in 1975. Subsequent studies confirmed that unrefreshing sleep is one of the most common symptoms in FMS and that sleep disturbance is one predictor of chronic widespread pain. Dr. Moldofsky's contribution in this issue reviews the animal and human experimental evidence that implicates sleep disturbances in the development of musculoskeletal pain syndromes and brings up to date the relationship among sleep deprivation, central nervous system neurotransmitters, and chronic pain states and fatigue.
Kawakita, Itoh, and Okada present studies that evaluate local changes in muscle as important in the generation of the TrP. They provide evidence that repeated eccentric exercise induces changes in muscle typical of TrPs and initiate changes that can result in peripheral nociceptor nerve receptor sensitization. They also propose that TrPs can occur in other tissues such as ligaments and periostium. Thus, they attempt to relate mechanical dysfunction with the cascade of events that eventually result in TrP formation.
Two primarily clinical papers are presented by John Jarrell and IMS outgoing President Dieter Pongratz. Dr. Jarrell has amassed a large amount of observational data from women with chronic pelvic pain to demonstrate that prior visceral disease and endometriosis are associated with a significantly higher number of areas of abdominal wall TrPs, establishing a clinically relevant example of a visceral-somatic pain syndrome in which body wall TrPs develop as a result of persistent visceral pain. Moreover, the body wall myofascial syndrome can persist long after the visceral component subsides, and it can mimic the visceral pain syndrome. Inactivation of abdominal wall TrPs reduces pain that appears to be visceral, but that clearly is body wall. Dr. Jarrell's observations have important implications for the treatment of chronic visceral pain syndromes such as endometriosis, interstitial cystitis, and irritable bowel syndrome because symptoms may arise from the abdominal wall muscle triggers and subside with TrP inactivation. Dr. Pongratz reviews the subject of muscle pain that arises from inflammatory myopathies, metabolic myopathies, and the hereditary myopathies, describing their clinical presentation, their pathologies, and their treatment.
Finally, in closing the Congress, I tried to address the enigma of the development of the TrP taut band and explore the mechanisms whereby acetylcholine and the sympathetic nervous system separately modulate the endplate noise characteristic of the taut band in the active TrP. I closed with some thoughts on the role of the Ryanidine calcium channel in modulating cytosolic concentrations of calcium and raised the possibility that channelopathies might play a role in the development of the TrP, in this way trying to point the way to further studies in the pathogenesis of MPS.
There is now a great deal of activity in both mechanistic research at the molecular level and clinical research in defining more clearly the role of MPS and FMS in clinical pain states. I expect that the presentations at the next Congress in Toledo, Spain, in 2010 will greatly extend and expand the work presented at this Congress and will be equally or even more stimulating to the field of muscle pain research and management.