Changes in morphine reward in a model of neuropathic pain

Cahill, Catherine M.; Xue, Ling; Grenier, Patrick; Magnussen, Claire; Lecour, S.; Olmstead, Mary C.

doi:10.1097/fbp.0b013e3283618ac8

Cited by 48 publications

(36 citation statements)

References 22 publications

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“…Evidence from a number of groups also suggests that the mesolimbic dopamine system modulates the perception of nociceptive information, the efficacy of pain medications, and the affective symptoms of chronic pain (Baliki et al, 2010, Cahill et al, 2013, Terzi et al, 2014). Dennis and Melzack (1983) first demonstrated that dopaminergic agents improve symptoms of pain and promote analgesia.…”

Section: Chronic Pain Modulates the Mesolimbic Circuitrymentioning

confidence: 99%

Modulation of pain, nociception, and analgesia by the brain reward center

2016

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The midbrain dopamine center comprises a key network for reward, salience, motivation, and mood. Evidence from various clinical and preclinical settings points to the midbrain dopamine circuit as an important modulator of pain perception and pain-induced anxiety and depression. This review summarizes recent findings that shed light to the neuroanatomical, electrophysiological and molecular adaptations that chronic pain conditions promote in the mesolimbic dopamine system. Chronic pain states induce changes in neuronal plasticity and functional connectivity in several parts of the brain reward center, including nucleus accumbens, the ventral tegmental area and the prefrontal cortex. Here, we discuss recent findings on the mechanisms involved in the perception of chronic pain, in pain-induced anxiety and depression, as well as in pain-killer addiction vulnerability. Several new studies also show that the mesolimbic dopamine circuit potently modulates responsiveness to opioids and antidepressants used for the treatment of chronic pain. We discuss recent data supporting a role of the brain reward pathway in treatment efficacy and we summarize novel findings on intracellular adaptations in the brain reward circuit under chronic pain states.

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Section: Chronic Pain Modulates the Mesolimbic Circuitrymentioning

confidence: 99%

Modulation of pain, nociception, and analgesia by the brain reward center

2016

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“…In animal models, chronic pain alters the motivation to obtain reward (Cahill et al, 2013;Wade et al, 2013) and leads to preference of larger infrequent rewards (Pais-Vieira et al, 2009). In experimental acute pain in humans, motivation to obtain reward was shown to be increased without affecting the self-reported hedonic response to reward (Gandhi et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Reward responsiveness in patients with chronic pain

Elvemo

Landrø

Borchgrevink

et al. 2015

European Journal of Pain

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Background: It is proposed that changes in reward processing in the brain are involved in the pathophysiology of pain based on experimental studies. The first aim of the present study was to investigate if reward drive and/or reward responsiveness was altered in patients with chronic pain (PCP) compared to controls matched for education, age and sex. The second aim was to investigate the relationship between reward processing and nucleus accumbens volume in PCP and controls. Nucleus accumbens is central in reward processing and its structure has been shown to be affected by chronic pain conditions in previous studies. Methods: Reward drive and responsiveness were assessed with the Behavioral Inhibition Scale/Behavioral Activation Scale, and nucleus accumbens volumes obtained from T1-weighted brain MRIs obtained at 3T in 19 PCP of heterogeneous aetiologies and 20 age-, sex-and education-matched healthy controls. Anhedonia was assessed with Beck's Depression Inventory II. Results: The PCP group had significantly reduced scores on the reward responsiveness, but not reward drive. There was a trend towards smaller nucleus accumbens volume in the PCP compared to control group. There was a significant positive partial correlation between reward responsiveness and nucleus accumbens volume in the PCP group adjusted for anhedonia, which was significantly different from the same relationship in the control group. Conclusions: Reward responsiveness is reduced in chronic pain patients of heterogeneous aetiology, and this reduction was associated with nucleus accumbens volume. Reduced reward responsiveness could be a marker of chronic pain vulnerability, and may indicate reduced opioid function.

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“…As described above, the pathogenesis of neuropathic pain and the effect of the disease on higher brain function have been widely investigated [26][27][28] ; however, the effect of neuropathic pain on peripheral organs remains unclear. We previously demonstrated that increased expression of uridine diphosphate glucuronosyltransferase (UGT)2B in the liver was a major cause of morphine resistance in neuropathic pain.…”

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confidence: 99%

Mechanism for Increased Expression of UGT2B in the Liver of Mice with Neuropathic Pain

Kaneta

Ochiai

Nagae

et al. 2016

Biological & Pharmaceutical Bulletin

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Approximately 30% of patients with cancer pain experience concurrent neuropathic pain. Since these patients are not sufficiently responsive to morphine, the development of an effective method of pain relief is urgently needed. Decreased function of the μ opioid receptor, which binds to the active metabolite of morphine M-6-G in the brain, has been proposed as a mechanism for morphine resistance. Previously, we pharmacokinetically examined morphine resistance in mice with neuropathic pain, and demonstrated that the brain morphine concentration was decreased, expression level of P-glycoprotein (P-gp) in the small intestine was increased, and expression level and activity of uridine diphosphate glucuronosyltransferase (UGT)2B in the liver were increased. In order to clarify the mechanism of the increased expression of UGT2B, we examined the phase of neuropathic pain during which UGT2B expression in the liver begins to increase, and whether this increased expression is nuclear receptor-mediated. The results of this study revealed that the increased expression of UGT2B in the liver occurred during the maintenance phase of neuropathic pain, suggesting that it may be caused by transcriptional regulation which was not accompanied by increased nuclear import of pregnane X receptor (PXR). Key words morphine; neuropathic pain; nuclear receptorIt has been reported that the onset of neuropathic pain is closely associated with the immune response around the damaged nerve. When a nerve is injured, histamine, inflammatory cytokines, and chemokines are released from mast cells located in the damaged nerve, inducing the activation and accumulation of neutrophils and macrophages to the nerve site. Subsequently, inflammatory cytokines and chemokines released from the accumulated cells sensitize the primary sensory nerves, 1,2) increasing the release of pain transmitters from the primary sensory nerve endings, resulting in an unusual enhancement of the effect of the pain transmitters on secondary sensory nerves. 3,4) The effect of pain transmitters on secondary sensory nerves is further augmented by the activation of microglia, 5-9) a type of glia cell, in the spinal cord. This accelerates the release of inflammatory cytokines and other factors. It has also been reported that expression of the ligand-gated ion channel pregnane 2 recepter (P2X) receptor is increased in activated microglia. 8,[10][11][12] This induces the release of brain-derived neurotrophic factor (BDNF) from microglia, which binds to the tyrosine kinase receptor B (TrkB) receptor on secondary sensory nerves, downregulating the expression of K-Cl cotransporter 2 (KCC2). 13,14) The reduced expression of KCC2 disinhibits GABAergic neurons, which suppress the sensation of pain under normal conditions, resulting in pain enhancement.15) The expression of P2X receptor and brain-derived neurotrophic factor is also increased by interferon regulatory factor 8 (IRF8), a transcription factor belonging to the interferon regulatory factor family. 16)A recent report states that t...

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Changes in morphine reward in a model of neuropathic pain

Cited by 48 publications

References 22 publications

Modulation of pain, nociception, and analgesia by the brain reward center

Modulation of pain, nociception, and analgesia by the brain reward center

Reward responsiveness in patients with chronic pain

Mechanism for Increased Expression of UGT2B in the Liver of Mice with Neuropathic Pain

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