Dataset Information

Striatal opioid receptor availability is related to acute and chronic pain perception in arthritis: does opioid adaptation increase resilience to chronic pain?

ABSTRACT: The experience of pain in humans is modulated by endogenous opioids, but it is largely unknown how the opioid system adapts to chronic pain states. Animal models of chronic pain point to upregulation of opioid receptors (OpR) in the brain, with unknown functional significance. We sought evidence for a similar relationship between chronic pain and OpR availability in humans. Using positron emission tomography and the radiotracer (11)C-diprenorphine, patients with arthritis pain (n = 17) and healthy controls (n = 9) underwent whole-brain positron emission tomography scanning to calculate parametric maps of OpR availability. Consistent with the upregulation hypothesis, within the arthritis group, greater OpR availability was found in the striatum (including the caudate) of patients reporting higher levels of recent chronic pain, as well as regions of interest in the descending opioidergic pathway including the anterior cingulate cortex, thalamus, and periaqueductal gray. The functional significance of striatal changes were clarified with respect to acute pain thresholds: data across patients and controls revealed that striatal OpR availability was related to reduced pain perception. These findings are consistent with the view that chronic pain may upregulate OpR availability to dampen pain. Finally, patients with arthritis pain, compared with healthy controls, had overall less OpR availability within the striatum specifically, consistent with the greater endogenous opioid binding that would be expected in chronic pain states. Our observational evidence points to the need for further studies to establish the causal relationship between chronic pain states and OpR adaptation.

SUBMITTER: Brown CA

PROVIDER: S-EPMC4933204 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Striatal opioid receptor availability is related to acute and chronic pain perception in arthritis: does opioid adaptation increase resilience to chronic pain?

Brown Christopher A CA Matthews Julian J Fairclough Michael M McMahon Adam A Barnett Elizabeth E Al-Kaysi Ali A El-Deredy Wael W Jones Anthony K P AKP

Pain 20151101 11

The experience of pain in humans is modulated by endogenous opioids, but it is largely unknown how the opioid system adapts to chronic pain states. Animal models of chronic pain point to upregulation of opioid receptors (OpR) in the brain, with unknown functional significance. We sought evidence for a similar relationship between chronic pain and OpR availability in humans. Using positron emission tomography and the radiotracer (11)C-diprenorphine, patients with arthritis pain (n = 17) and healt ...[more]

PMID: 26176892

Similar Datasets

Project description:The parabrachial (PB) complex mediates both ascending nociceptive signaling and descending pain modulatory information in the affective/emotional pain pathway. We have recently reported that chronic pain is associated with amplified activity of PB neurons in a rat model of neuropathic pain. Here we demonstrate that similar activity amplification occurs in mice, and that this is related to suppressed inhibition to lateral parabrachial (LPB) neurons from the CeA in animals of either sex. Animals with pain after chronic constriction injury of the infraorbital nerve (CCI-Pain) displayed higher spontaneous and evoked activity in PB neurons, and a dramatic increase in after-discharges, responses that far outlast the stimulus, compared with controls. LPB neurons in CCI-Pain animals showed a reduction in inhibitory, GABAergic inputs. We show that, in both rats and mice, LPB contains few GABAergic neurons, and that most of its GABAergic inputs arise from CeA. These CeA GABA neurons express dynorphin, somatostatin, and/or corticotropin releasing hormone. We find that the efficacy of this CeA-LPB pathway is suppressed in chronic pain. Further, optogenetically stimulating this pathway suppresses acute pain, and inhibiting it, in naive animals, evokes pain behaviors. These findings demonstrate that the CeA-LPB pathway is critically involved in pain regulation, and in the pathogenesis of chronic pain.SIGNIFICANCE STATEMENT We describe a novel pathway, consisting of inhibition by dynorphin, somatostatin, and corticotropin-releasing hormone-expressing neurons in the CeA that project to the parabrachial nucleus. We show that this pathway regulates the activity of pain-related neurons in parabrachial nucleus, and that, in chronic pain, this inhibitory pathway is suppressed, and that this suppression is causally related to pain perception. We propose that this amygdalo-parabrachial pathway is a key regulator of both chronic and acute pain, and a novel target for pain relief.

Project description:The crisis of prescription opioid (PO) related harms has focused attention toward identifying and treating high-risk populations. This review aims to synthesize systematic reviews on the epidemiology and clinical management of comorbid chronic pain and PO or other substance misuse.A systematic database search was conducted to identify systematic reviews published between 2000 and 2016. Eligible studies were systematic reviews related to chronic non-cancer pain and PO or other substance misuse. Evidence from the included reviews was synthesized according to epidemiology and clinical management themes.Of 1908 identified articles, 18 systematic reviews were eligible for final inclusion. Two meta-analyses estimated the prevalence of chronic non-cancer pain in individuals using POs non-medically to be approximately 48% to 60%, which is substantially higher than the prevalence of chronic non-cancer pain in general population samples (11% to 19%). Five systematic reviews estimated the rates of PO or other opioid use in chronic pain populations with substantial variation in results (0.05% to 81%), likely due to widely varying definitions of dependence, substance use disorder, misuse, addiction, and abuse. Several clinical assessment and treatment approaches were identified, including: standardized assessment instruments; urine drug testing; medication counts; prescription drug monitoring programs; blood level monitoring; treatment agreements; opioid selection; dosing and dispensing strategies; and opioid agonist treatment. However, the reviews commonly noted serious limitations, inconsistencies, and imprecision of studies, and a lack of evidence on effectiveness or clinical utility for the majority of these strategies.Overall, current systematic reviews have found a lack of high-quality evidence or consistent findings on the prevalence, risk factors, and optimal clinical assessment and treatment approaches related to concurrent chronic pain and substance misuse. Given the role of systematic reviews in guiding evidence-based medicine and health policy, there is an urgent need for high-quality primary research to guide future systematic reviews to address the escalating epidemic of harms related to chronic pain and substance misuse.

Dataset Information

Striatal opioid receptor availability is related to acute and chronic pain perception in arthritis: does opioid adaptation increase resilience to chronic pain?

Publications

Striatal opioid receptor availability is related to acute and chronic pain perception in arthritis: does opioid adaptation increase resilience to chronic pain?

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets