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Are Opioids Needed to Treat Chronic Low Back Pain? A Review of Treatment Options and Analgesics in Development.

ABSTRACT: The continued prevalence of chronic low back pain (CLBP) is a testament to our lack of understanding of the potential causes, leading to significant treatment challenges. CLBP is the leading cause of years lived with disability and the fifth leading cause of disability-adjusted life-years. No single non-pharmacologic, pharmacologic, or interventional therapy has proven effective as treatment for the majority of patients with CLBP. Although non-pharmacologic therapies are generally helpful, they are often ineffective as monotherapy and many patients lack adequate access to these treatments. Noninvasive treatment measures supported by evidence include physical and chiropractic therapy, yoga, acupuncture, and non-opioid and opioid pharmacologic therapy; data suggest a moderate benefit, at most, for any of these therapies. Until our understanding of the pathophysiology and treatment of CLBP advances, clinicians must continue to utilize rational multimodal treatment protocols. Recent Centers for Disease Control and Prevention guidelines for opioid prescribing recommend that opioids not be utilized as first-line therapy and to limit the doses when possible for fear of bothersome or dangerous adverse effects. In combination with the current opioid crisis, this has caused providers to minimize or eliminate opioid therapy when treating patients with chronic pain, leaving many patients suffering despite optimal nonopioid therapies. Therefore, there remains an unmet need for effective and tolerable opioid receptor agonists for the treatment of CLBP with improved safety properties over legacy opioids. There are several such agents in development, including opioids and other agents with novel mechanisms of action. This review critiques non-pharmacologic and pharmacologic treatment modalities for CLBP and examines the potential of novel opioids and other analgesics that may be a useful addition to the treatment options for patients with chronic pain.

SUBMITTER: Gudin J

PROVIDER: S-EPMC7234959 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Are Opioids Needed to Treat Chronic Low Back Pain? A Review of Treatment Options and Analgesics in Development.

Gudin Jeffrey J Kaufman Andrew G AG Datta Samyadev S

Journal of pain research 20200514

The continued prevalence of chronic low back pain (CLBP) is a testament to our lack of understanding of the potential causes, leading to significant treatment challenges. CLBP is the leading cause of years lived with disability and the fifth leading cause of disability-adjusted life-years. No single non-pharmacologic, pharmacologic, or interventional therapy has proven effective as treatment for the majority of patients with CLBP. Although non-pharmacologic therapies are generally helpful, they ...[more]

PMID: 32523371

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Project description:We recently showed that patients with different chronic pain conditions (such as chronic low back pain, fibromyalgia, migraine and Gulf War illness) demonstrated elevated brain and/or spinal cord levels of the glial marker 18-kDa translocator protein (TSPO), which suggests that neuroinflammation might be a pervasive phenomenon observable across multiple aetiologically heterogeneous pain disorders. Interestingly, the spatial distribution of this neuroinflammatory signal appears to exhibit a degree of disease specificity (e.g. with respect to the involvement of the primary somatosensory cortex), suggesting that different pain conditions may exhibit distinct 'neuroinflammatory signatures'. To explore this hypothesis further, we tested whether neuroinflammatory signal can characterize putative aetiological subtypes of chronic low back pain patients based on clinical presentation. Specifically, we explored neuroinflammation in patients whose chronic low back pain either did or did not radiate to the leg (i.e. 'radicular' versus 'axial' back pain). Fifty-four patients with chronic low back pain, 26 with axial back pain [43.7 ± 16.6 years old (mean ± SD)] and 28 with radicular back pain (48.3 ± 13.2 years old), underwent PET/MRI with 11C-PBR28, a second-generation radioligand for TSPO. 11C-PBR28 signal was quantified using standardized uptake values ratio (validated against volume of distribution ratio; n = 23). Functional MRI data were collected simultaneously to the 11C-PBR28 data (i) to functionally localize the primary somatosensory cortex back and leg subregions; and (ii) to perform functional connectivity analyses (in order to investigate possible neurophysiological correlations of the neuroinflammatory signal). PET and functional MRI measures were compared across groups, cross-correlated with one another and with the severity of 'fibromyalgianess' (i.e. the degree of pain centralization, or 'nociplastic pain'). Furthermore, statistical mediation models were used to explore possible causal relationships between these three variables. For the primary somatosensory cortex representation of back/leg, 11C-PBR28 PET signal and functional connectivity to the thalamus were: (i) higher in radicular compared to axial back pain patients; (ii) positively correlated with each other; (iii) positively correlated with fibromyalgianess scores, across groups; and finally (iv) fibromyalgianess mediated the association between 11C-PBR28 PET signal and primary somatosensory cortex-thalamus connectivity across groups. Our findings support the existence of 'neuroinflammatory signatures' that are accompanied by neurophysiological changes and correlate with clinical presentation (in particular, with the degree of nociplastic pain) in chronic pain patients. These signatures may contribute to the subtyping of distinct pain syndromes and also provide information about interindividual variability in neuroimmune brain signals, within diagnostic groups, that could eventually serve as targets for mechanism-based precision medicine approaches.

Dataset Information

Are Opioids Needed to Treat Chronic Low Back Pain? A Review of Treatment Options and Analgesics in Development.

Publications

Are Opioids Needed to Treat Chronic Low Back Pain? A Review of Treatment Options and Analgesics in Development.

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