Chronic Pain and Opioid Analgesic Use

IntroductionIn the USA, opioid analgesic use and overdoses have increased dramatically. One rapidly expanding strategy to manage chronic pain in the context of this epidemic is medical cannabis. Cannabis has analgesic effects, but it also has potential adverse effects. Further, its impact on opioid analgesic use is not well studied. Managing pain in people living with HIV is particularly challenging, given the high prevalence of opioid analgesic and cannabis use. This study’s overarching goal is to understand how medical cannabis use affects opioid analgesic use, with attention to Δ9-tetrahydrocannabinol and cannabidiol content, HIV outcomes and adverse events.Methods and analysesWe are conducting a cohort study of 250 adults with and without HIV infection with (a) severe or chronic pain, (b) current opioid use and (c) who are newly certified for medical cannabis in New York. Over 18 months, we collect data via in-person visits every 3 months and web-based questionnaires every 2 weeks. Data sources include: questionnaires; medical, pharmacy and Prescription Monitoring Program records; urine and blood samples; and physical function tests. Using marginal structural models and comparisons within participants’ 2-week time periods (unit of analysis), we will examine how medical cannabis use (primary exposure) affects (1) opioid analgesic use (primary outcome), (2) HIV outcomes (HIV viral load, CD4 count, antiretroviral adherence, HIV risk behaviours) and (3) adverse events (cannabis use disorder, illicit drug use, diversion, overdose/deaths, accidents/injuries, acute care utilisation).Ethics and disseminationThis study is approved by the Montefiore Medical Center/Albert Einstein College of Medicine institutional review board. Findings will be disseminated through conferences, peer-reviewed publications and meetings with medical cannabis stakeholders.Trial registration numberClinicalTrials.gov Registry (NCT03268551); Pre-results.

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Anxiety enhances pain in a model of osteoarthritis and is associated with altered endogenous opioid function and reduced opioid analgesia

10.1101/2020.04.24.057570 ◽

2020 ◽

Author(s):

Amanda Lillywhite ◽

Stephen G. Woodhams ◽

David J. G. Watson ◽

Li Li ◽

James J. Burston ◽

...

Keyword(s):

Chronic Pain ◽

Opioid Analgesic ◽

Opioid Analgesics ◽

Endogenous Opioid System ◽

High Anxiety ◽

Endogenous Opioid ◽

Pain Behaviour ◽

Chronic Pain Patients ◽

Pain Patients ◽

Analgesic Use

AbstractChronic pain states such as osteoarthritis (OA) are often associated with negative affect, including anxiety and depression. This is, in turn, associated with greater opioid analgesic use, potentially contributing to current and future opioid crises. We utilise an animal model to investigate the neurobiological mechanisms underlying increased opioid use associated with high anxiety and chronic pain.Combining a genetic model of negative affect, the Wistar Kyoto (WKY) rat, and intra-articular injection of monosodium iodoacetate (MIA; 1mg), our model of high anxiety and augmented OA-like pain behaviour mirrors the clinical problem. Effects of morphine (0.5-6mg.kg-1) on pain behaviour and spinal nociceptive neuronal activity were determined in WKY rats, and normo-anxiety Wistar rats, 3 weeks after MIA injection. WKY rats developed augmented OA-like pain, and had blunted inhibitory responses to morphine, when compared to Wistar rats. Potential alterations in endogenous opioid function were probed via systemic blockade of opioid receptors with naloxone (0.1-1mg.kg-1), quantification of circulating levels of β-endorphin, and determination of spinal expression of the mu-opioid receptor (MOR). These studies revealed increased opioidergic tone, and increased spinal desensitization of MORs via the master phosphorylation site at serine residue 375, in this model.We demonstrate attenuated MOR function in the absence of previous exogenous opioid ligand exposure in our model of high anxiety and OA-like pain, which may account for reduced analgesic effect of morphine and provide a potential explanation for increased opioid analgesic intake in high anxiety chronic pain patients.Significance StatementChronic pain affects large numbers of people, and pain management often relies on poorly effective opioid analgesics, the iatrogenic effects of which are increasingly recognised. The endogenous opioid system - the target for exogenous opioid analgesics - plays key roles in emotional affective states and pain control, but the complex interplay between anxiety, chronic pain, and endogenous opioid system function is challenging to study in people. Here, we have addressed this using a clinically-relevant experimental model. Anxiety-like behaviour was associated with increased chronic arthritis-like pain behaviour, altered opioid receptor function, and reduced efficacy of opioid analgesics. We provide new evidence, which may explain why chronic pain patients with comorbid high anxiety have higher opioid analgesic use.

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