Decreased Central μ-Opioid Receptor Availability in Fibromyalgia

The underlying neurophysiology of acute pain is fairly well characterized, whereas the central mechanisms operative in chronic pain states are less well understood. Fibromyalgia (FM), a common chronic pain condition characterized by widespread pain, is thought to originate largely from altered central neurotransmission. We compare a sample of 17 FM patients and 17 age- and sex-matched healthy controls, using μ-opioid receptor (MOR) positron emission tomography. We demonstrate that FM patients display reduced MOR binding potential (BP) within several regions known to play a role in pain modulation, including the nucleus accumbens, the amygdala, and the dorsal cingulate. MOR BP in the accumbens of FM patients was negatively correlated with affective pain ratings. Moreover, MOR BP throughout the cingulate and the striatum was also negatively correlated with the relative amount of affective pain (McGill, affective score/sensory score) within these patients. These findings indicate altered endogenous opioid analgesic activity in FM and suggest a possible reason for why exogenous opiates appear to have reduced efficacy in this population.

[1]  B. Vogt.  Pain and emotion interactions in subregions of the cingulate gyrus , 2005, Nature Reviews Neuroscience.

[2]  Frode Willoch,et al.  Central poststroke pain and reduced opioid receptor binding within pain processing circuitries: a [11C]diprenorphine PET study , 2004, Pain.

[3]  D. Clauw,et al.  Cerebrospinal fluid levels of opioid peptides in fibromyalgia and chronic low back pain , 2004, BMC musculoskeletal disorders.

[4]  David A. Williams,et al.  Differences in unpleasantness induced by experimental pressure pain between patients with fibromyalgia and healthy controls , 2005, European journal of pain.

[5]  R. Koeppe,et al.  Regulation of human affective responses by anterior cingulate and limbic mu-opioid neurotransmission. , 2003, Archives of general psychiatry.

[6]  P. Tugwell,et al.  The American College of Rheumatology 1990 Criteria for the Classification of Fibromyalgia. Report of the Multicenter Criteria Committee. , 1990, Arthritis and rheumatism.

[7]  J. García-Sevilla,et al.  Increased density of μ-opioid receptors in the postmortem brain of suicide victims , 1995, Brain Research.

[8]  Pierre Arsenault,et al.  Widespread pain in fibromyalgia is related to a deficit of endogenous pain inhibition , 2005, Pain.

[9]  Daniel J Clauw,et al.  Functional magnetic resonance imaging evidence of augmented pain processing in fibromyalgia. , 2002, Arthritis and rheumatism.

[10]  B. H. Manning.  A Lateralized Deficit in Morphine Antinociception after Unilateral Inactivation of the Central Amygdala , 1998, The Journal of Neuroscience.

[11]  David A. Williams,et al.  Subgrouping of fibromyalgia patients on the basis of pressure-pain thresholds and psychological factors. , 2003, Arthritis and rheumatism.

[12]  B Bromm,et al.  Middle and long latency somatosensory evoked potentials after painful laser stimulation in patients with fibromyalgia syndrome. , 1996, Electroencephalography and clinical neurophysiology.

[13]  Robert A Koeppe,et al.  Dysregulation of endogenous opioid emotion regulation circuitry in major depression in women. , 2006, Archives of general psychiatry.

[14]  G. Chrousos,et al.  Chronic pain and fatigue syndromes: overlapping clinical and neuroendocrine features and potential pathogenic mechanisms. , 1997, Neuroimmunomodulation.

[15]  H. Fields.  State-dependent opioid control of pain , 2004, Nature Reviews Neuroscience.

[16]  B. Vogt,et al.  Localization of Mu and Delta Opioid Receptors to Anterior Cingulate Afferents and Projection Neurons and Input/Output Model of Mu Regulation , 1995, Experimental Neurology.

[17]  Jason Steffener,et al.  Functional imaging of pain in patients with primary fibromyalgia. , 2004, The Journal of rheumatology.

[18]  Anat Biegon,et al.  Regionally selective increases in μ opioid receptor density in the brains of suicide victims , 1990, Brain Research.

[19]  N. Volkow,et al.  Distribution Volume Ratios without Blood Sampling from Graphical Analysis of PET Data , 1996, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[20]  Till Sprenger,et al.  Opioidergic activation in the medial pain system after heat pain , 2006, PAIN.

[21]  M. Bushnell,et al.  Pain affect encoded in human anterior cingulate but not somatosensory cortex. , 1997, Science.

[22]  J. Levine,et al.  Antinociception produced by an ascending spino-supraspinal pathway , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[23]  Karl J. Friston,et al.  Comparing Functional (PET) Images: The Assessment of Significant Change , 1991, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[24]  M. Mintun,et al.  Automated detection of the intercommissural line for stereotactic localization of functional brain images. , 1993, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[25]  Steven Laureys,et al.  Posterior cingulate, precuneal and retrosplenial cortices: cytology and components of the neural network correlates of consciousness. , 2005, Progress in brain research.

[26]  Alan C. Evans,et al.  A Three-Dimensional Statistical Analysis for CBF Activation Studies in Human Brain , 1992, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[27]  H N Wagner,et al.  Radiosynthesis of an opiate receptor binding radiotracer: [11C]carfentanil. , 1985, The International journal of applied radiation and isotopes.

[28]  N. Muilenburg.  Management of fibromyalgia. , 2000, Annals of internal medicine.

[29]  Roland Peyron,et al.  Differential brain opioid receptor availability in central and peripheral neuropathic pain , 2007, Pain.

[30]  J. McDougall,et al.  Chronic arthritis down-regulates peripheral mu-opioid receptor expression with concomitant loss of endomorphin 1 antinociception. , 2005, Arthritis and rheumatism.

[31]  H. Watabe,et al.  Cerebral decreases in opioid receptor binding in patients with central neuropathic pain measured by [11C]diprenorphine binding and PET , 2004, European journal of pain.

[32]  Is fibromyalgia a distinct clinical entity? The disapproving rheumatologist's evidence. , 1999, Bailliere's best practice & research. Clinical rheumatology.

[33]  I. Russell,et al.  Cerebrospinal fluid biogenic amine metabolites in fibromyalgia/fibrositis syndrome and rheumatoid arthritis. , 1992, Arthritis and rheumatism.

[34]  P. Fuchs,et al.  Selective regulation of pain affect following activation of the opioid anterior cingulate cortex system , 2006, Experimental Neurology.

[35]  F. Wolfe,et al.  The prevalence and characteristics of fibromyalgia in the general population. , 1995, Arthritis and rheumatism.

[36]  L. Jan,et al.  Functional Dissociation of μ Opioid Receptor Signaling and Endocytosis Implications for the Biology of Opiate Tolerance and Addiction , 1999, Neuron.

[37]  Joshua A. Bueller,et al.  Regional Mu Opioid Receptor Regulation of Sensory and Affective Dimensions of Pain , 2001, Science.

[38]  D. Jewett.  A simple synthesis of [11C]carfentanil using an extraction disk instead of HPLC. , 2001, Nuclear medicine and biology.

[39]  Ronald Melzack,et al.  The short-form McGill pain questionnaire , 1987, Pain.

[40]  David A. Williams,et al.  The relationship between depression, clinical pain, and experimental pain in a chronic pain cohort. , 2005, Arthritis and rheumatism.

[41]  Daniel J Clauw,et al.  Increased pain sensitivity in fibromyalgia: effects of stimulus type and mode of presentation , 2003, Pain.

[42]  S. Luthra,et al.  Changes in central opioid receptor binding in relation to inflammation and pain in patients with rheumatoid arthritis. , 1994, British journal of rheumatology.

[43]  Clifford J. Woolf,et al.  Pain: Moving from Symptom Control toward Mechanism-Specific Pharmacologic Management , 2004, Annals of Internal Medicine.