Changes in Central Opioid Receptor Binding in Relation to Inflammation and Pain in Patients With Rheumatoid Arthritis

Jones, Anthony; Cunningham, VJ; Ha-Kawa, Sang Kil; Fujiwara, Tetsuro; Luthra, SK; Silva, S.; Derbyshire, Stuart; Jones, T.S.

doi:10.1093/rheumatology/33.10.909

Cited by 148 publications

(86 citation statements)

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“…Reductions in blood flow to this region, as well as spontaneous neuronal hyperactivity have been reported in both patients and animal models of persistent neuropathic pain, suggesting reduced inhibitory neural activity (Guilbaud et al, 1990;Rinaldi et al, 1991;Iadarola et al, 1995;Paulson et al, 2002). In line with the hypothesis that reduced thalamic inhibition is present in persistent pain states, studies in patients with trigeminal neuropathy have found thalamic gray matter loss, dysregulated thalamocortical connectivity, and reduced concentrations of GABA, a major neurotransmitter mediating fast inhibition, in the thalamus (Gustin et al, 2011;Henderson et al, 2013). Although a considerable amount of severe chronic back pain may be neuropathic, at present it is not known whether these findings can be extended to CNBP (Schmidt et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

“…The reductions in opioid receptor availability in these chronic pain conditions have been interpreted as reflecting persistent endogenous opioid system activation and a downregulation of these receptor sites. Indeed, after successful treatment, recovery of opioid receptor availability has been shown in small samples of chronic pain patients in parallel with improvements in pain report (Jones et al, 1994(Jones et al, , 1999.…”

Section: Introductionmentioning

confidence: 99%

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Alterations in Endogenous Opioid Functional Measures in Chronic Back Pain

et al. 2013

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The absence of consistent end organ abnormalities in many chronic pain syndromes has led to a search for maladaptive CNS mechanisms that may explain their clinical presentations and course. Here, we addressed the role of brain regional -opioid receptor-mediated neurotransmission, one of the best recognized mechanisms of pain regulation, in chronic back pain in human subjects. We compared -opioid receptor availability in vivo at baseline, during pain expectation, and with moderate levels of sustained pain in 16 patients with chronic nonspecific back pain (CNBP) and in 16 age-and gender-matched healthy control subjects, using the -opioid receptor-selective radioligand [ 11 C]carfentanil and positron emission tomography. We found that CNBP patients showed baseline increases in thalamic -opioid receptor availability, contrary to a previously studied sample of patients diagnosed with fibromyalgia. During both pain expectation and sustained pain challenges, CNBP patients showed regional reductions in the capacity to activate this neurotransmitter system compared with their control sample, further associated with clinical pain and affective state ratings. Our results demonstrate heterogeneity in endogenous opioid system functional measures across pain conditions, and alterations in both receptor availability and endogenous opioid function in CNBP that are relevant to the clinical presentation of these patients and the effects of opioid analgesics on -opioid receptors.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Alterations in Endogenous Opioid Functional Measures in Chronic Back Pain

et al. 2013

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“…Two other chronic pain states, rheumatoid arthritis (Jones et al, 1994) and central neuropathic pain following stroke (Jones et al, 2004;Willoch et al, 2004), also display a reduction in opioid receptor BP within the CNS, as measured with the nonselective opioid receptor radiotracer […”

Section: Discussionmentioning

confidence: 99%

Decreased Central μ-Opioid Receptor Availability in Fibromyalgia

Harris¹,

Clauw²,

Scott³

et al. 2007

J. Neurosci.

443

277

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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 -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.

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“…Previous studies in healthy control subjects have demonstrated high uptake of [11C] diprenorphine in diffuse cortical areas known from postmortem studies to have high concentrations of opioid receptors [36], particularly in subcortical (thalamus) and cortical (insula, prefrontal, and ACC) components of the affective pain network [12]. Chronic pain studies have demonstrated decreased [11C]diprenorphine binding potential (BP: the ratio of receptor occupancy [B max ] to affinity [K D ]) in brain regions associated with the affective pain network (insula, ACC and frontal lobe) during pain states when compared to non-pain states [13,15,41]. Decreased [11C]diprenorphine BP is hypothesized to represent increased binding of opioid receptors by endogenous opioids.…”

Section: Discussionmentioning

confidence: 99%

A combined [11C]diprenorphine PET study and fMRI study of acupuncture analgesia

Dougherty

Kong

Webb

et al. 2008

Behavioural Brain Research

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Functional neuroimaging studies suggest that a lateral network in the brain is associated with the sensory aspects of pain perception while a medial network is associated with affective aspects. The highest concentration of opioid receptors is in the medial network. There is significant evidence that endogenous opioids are central to the experience of pain and analgesia. We applied an integrative multimodal imaging approach during acupuncture. We found functional magnetic resonance imaging signal changes in the orbitofrontal cortex, insula, and pons and [11C]diprenorphine positron emission tomography signal changes in the orbitofrontal cortex, medial prefrontal cortex, insula, thalamus, and anterior cingulate cortex. These findings include brain regions within both the lateral and medial pain networks.

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Changes in Central Opioid Receptor Binding in Relation to Inflammation and Pain in Patients With Rheumatoid Arthritis

Cited by 148 publications

References 0 publications

Alterations in Endogenous Opioid Functional Measures in Chronic Back Pain

Alterations in Endogenous Opioid Functional Measures in Chronic Back Pain

Decreased Central μ-Opioid Receptor Availability in Fibromyalgia

A combined [11C]diprenorphine PET study and fMRI study of acupuncture analgesia

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