Opioid use disorder and the brain: a clinical perspective

Herlinger, Katherine; Lingford-Hughes, Anne

doi:10.1111/add.15636

Cited by 20 publications

(12 citation statements)

References 98 publications

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“…Yet, following a brief period of abstinence, they had mild but increased signs of withdrawal and worse mental well-being. Both human and rodent model evidence indicates the causal involvement of the mesocorticolimbic circuit in chronic pain [11][12][13][14][15][16] , and this circuit is the main target of opioid exposure leading to OUD 17,18,22 . Thus, the change in ongoing activity and network dynamics observed in CBP+O following abstinence should be cast in the context of similar knowledge in OUD and SUD.…”

Section: Discussionmentioning

confidence: 99%

“…Each imparts a massive societal cost 9,10 , and their combination may impart an even greater cost. Our group has demonstrated that the development of chronic pain involves mesocorticolimbic plasticity, including the limbic amygdala, hippocampus, nucleus accumbens (NAc), and associated cortical circuits: medial prefrontal cortex (mPFC) and posterior cingulate, precuneus cortex [11][12][13][14][15][16] . Interestingly, these same circuits are strongly implicated in OUD, especially the dopaminergic ventral tegmental area (VTA), NAc, and mPFC circuit 17,18 .…”

Section: Mainmentioning

confidence: 99%

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Neuropsychology of chronic back pain managed with long-term opioid use

Baliki,

Vigotsky,

Rached

et al. 2024

Preprint

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Chronic pain is commonly treated with long-term opioids, but the neuropsychological outcomes associated with stable long-duration opioid use remain unclear. Here, we contrasted the psychological profiles, brain activity, and brain structure of 70 chronic back pain patients on opioids (CBP+O, average opioid exposure 6.2 years) with 70 patients managing their pain without opioids. CBP+O exhibited moderately worse psychological profiles and small differences in brain morphology. However, CBP+O had starkly different spontaneous brain activity, dominated by increased mesocorticolimbic and decreased dorsolateral-prefrontal activity, even after controlling for pain intensity and duration. These differences strongly reflected cortical opioid and serotonin receptor densities and mapped to two antagonistic resting-state circuits. The circuits’ dynamics were explained by mesocorticolimbic activity and reflected negative affect. We reassessed a sub-group of CBP+O after they briefly abstained from taking opioids. Network dynamics, but not spontaneous activity, reflected exacerbated signs of withdrawal. Our results have implications for the management and tapering of opioids in chronic pain.

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Section: Discussionmentioning

confidence: 99%

Section: Mainmentioning

confidence: 99%

Neuropsychology of chronic back pain managed with long-term opioid use

Baliki,

Vigotsky,

Rached

et al. 2024

Preprint

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“…The issue of opioid use and the negative impact on neuropsychological functions, including memory, is well known [ 47 ]. In the present study, approximately one-third of patients had complaints about reduced memory.…”

Section: Discussionmentioning

confidence: 99%

Change in self-reported somatic symptoms among patients in opioid maintenance treatment from baseline to 1-year follow-up

Bjørnestad,

Vederhus,

Clausen

2024

BMC Psychiatry

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Background High somatic comorbidity is common among patients in treatment for opioid use disorder (OUD). The present study aims to investigate changes in self-reported somatic health conditions and somatic symptoms among patients entering opioid maintenance treatment (OMT) programs. Methods We used data from the Norwegian Cohort of Patients in OMT and Other Drug Treatment (NorComt) study. Of 283 patients who entered OMT, 176 were included for analysis at a 1-year follow-up. Participants provided self-reported data during structured interviews on somatic conditions, somatic symptoms, substance use severity measures, and mental distress. A multivariable linear regression analysis identified factors associated with changes in the burden of somatic symptoms. Results Patients entering OMT reported a high prevalence of somatic conditions at the beginning of treatment, with 3 of 5 patients reporting at least one. The most prevalent condition was hepatitis C, followed by asthma and high blood pressure. Patients reported experiencing a high number of somatic symptoms. The intensity of these symptoms varied across a wide spectrum, with oral health complaints and reduced memory perceived as the most problematic. Overall, for the entire sample, there was no significant change in somatic symptoms from baseline to 1 year. Further analysis indicated that those who reported a higher burden of somatic symptoms at baseline had the greatest improvement at the 1-year follow-up. A higher number of somatic conditions and higher mental distress at baseline was associated with improvements in somatic symptoms burden at follow-up. Conclusions Patients in OMT report a range of somatic conditions and somatic symptoms. Given the wide range of symptoms reported by patients in OMT, including some at high intensity levels, healthcare providers should take into consideration the somatic healthcare needs of individuals in OMT populations. Clinical trial registration Clinicaltrials.gov no. NCT05182918. Registered 10/01/2022 (the study was retrospectively registered).

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“…Exogenous opioids have been used successfully for clinical management of pain. The ability of such opioids to produce euphoria presents high risk of abuse and likelihood of developing opioid-use disorder (OUD) [4]. However, the need for pain relief is critical with an estimated over 51 million US adults suffering chronic pain symptoms, resulting in problematic prescription opioid rates [5].…”

Section: Introductionmentioning

confidence: 99%

Modulation of endogenous opioid signaling by inhibitors of puromycin sensitive aminopeptidase

Singh,

Jiang,

Williams

et al. 2024

Preprint

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The endogenous opioid system regulates pain through local release of neuropeptides and modulation of their action on opioid receptors. However, the effect of opioid peptides, the enkephalins, is short-lived due to their rapid hydrolysis by enkephalin-degrading enzymes. In turn, an innovative approach to the management of pain would be to increase the local concentration and prolong the stability of enkephalins by preventing their inactivation by neural enkephalinases such as puromycin sensitive aminopeptidase (PSA). Our previous structure-activity relationship studies offered the S-diphenylmethyl cysteinyl derivative of puromycin (20) as a nanomolar inhibitor of PSA. This chemical class, however, suffered from undesirable metabolism to nephrotoxic puromycin aminonucleoside (PAN). To prevent such toxicity, we designed and synthesized 5′-chloro substituted derivatives. The compounds retained the PSA inhibitory potency of the corresponding 5′-hydroxy analogs and had improved selectivity toward PSA. In vivo treatment with the lead compound 19 caused significantly reduced pain response in antinociception assays, alone and in combination with Met-enkephalin. The analgesic effect was reversed by the opioid antagonist naloxone, suggesting the involvement of opioid receptors. Further, PSA inhibition by compound 19 in brain slices caused local increase in endogenous enkephalin levels, corroborating our rationale. Pharmacokinetic assessment of compound 19 showed desirable plasma stability and identified the cysteinyl sulfur as the principal site of metabolic liability. We gained additional insight into inhibitor-PSA interactions by molecular modeling, which underscored the importance of bulky aromatic amino acid in puromycin scaffold. The results of this study strongly support our rationale for the development of PSA inhibitors for effective pain management.

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Opioid use disorder and the brain: a clinical perspective

Cited by 20 publications

References 98 publications

Neuropsychology of chronic back pain managed with long-term opioid use

Neuropsychology of chronic back pain managed with long-term opioid use

Change in self-reported somatic symptoms among patients in opioid maintenance treatment from baseline to 1-year follow-up

Modulation of endogenous opioid signaling by inhibitors of puromycin sensitive aminopeptidase

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