Translational research : the journal of laboratory and clinical medicine
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Chronic back and neck pain are highly prevalent conditions that are among the largest drivers of physical disability and cost in the world. Recent clinical practice guidelines recommend use of non-pharmacologic treatments to decrease pain and improve physical function for individuals with back and neck pain. However, delivery of these treatments remains a challenge because common care delivery models for back and neck pain incentivize treatments that are not in the best interests of patients, the overall health system, or society. ⋯ Second, we characterize current use patterns for non-pharmacologic treatments and identify potential barriers to their delivery. Addressing these barriers will require coordinated efforts from multiple stakeholders to prioritize evidence-based non-pharmacologic treatment approaches over low value care for back and neck pain. These stakeholders include patients, health care providers, health care organizations, administrators, payers, policymakers and researchers.
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T-type calcium channels regulate neuronal excitability and are important contributors of pain processing. CaV3.2 channels are the major isoform expressed in nonpeptidergic and peptidergic nociceptive neurons and are emerging as promising targets for pain treatment. ⋯ Targeting the proteins that regulate the trafficking or transcription, and the ones that modify the channels via post-translational modifications are alternative means to regulate expression and function of CaV3.2 channels and hence to develop new drugs to control pain. Here we synthesize data supporting a role for CaV3.2 in numerous pain modalities and then discuss emerging opportunities for the indirect targeting of CaV3.2 channels.
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Opioids are commonly prescribed for the management of patients with chronic noncancer pain. Despite the potential analgesic benefits of opioids, long-term opioid therapy (LTOT) may be accompanied by problems such as opioid misuse and opioid use disorder (OUD). In this review, we begin with a description of opioid misuse and OUD and the patient-specific factors associated with these problems among patients with chronic pain. ⋯ Several psychological factors have been found to be associated with opioid use problems in patients with chronic pain, and evidence indicates that patients presenting with psychological disturbances are particularly at risk of transitioning to long-term opioid use, engaging in opioid misuse behaviors, and developing OUD. The biological factors that might underlie the association between psychological disturbances and opioid use problems in patients with chronic pain have yet to be fully elucidated, but a growing number of studies suggest that dysfunctions in reward, appetitive, autonomic, and neurocognitive systems might be involved. We end with an overview of specific types of psychological interventions that have been put forward to prevent or reduce the occurrence of opioid misuse and OUD in patients with chronic pain who are prescribed LTOT.
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Nociception and opioid antinociception in females are pliable processes, varying qualitatively and quantitatively over the reproductive cycle. Spinal estrogenic signaling via membrane estrogen receptors (mERs), in combination with multiple other signaling molecules [spinal dynorphin, kappa-opioid receptors (KOR), glutamate and metabotropic glutamate receptor 1 (mGluR1)], appears to function as a master coordinator, parsing functionality between pronociception and antinociception. This provides a window into pharmacologically accessing intrinsic opioid analgesic/anti-allodynic systems. ⋯ Aromatase-mERα oligomers are also plentiful, in a central nervous system region-specific fashion. These can be independently regulated and allow estrogens to act intracellularly within the same signaling complex in which they are synthesized, explaining asynchronous relationships between circulating estrogens and central nervous system estrogen functionalities. Observations with EM2 highlight the translational relevance of extensively characterizing exogenous responsiveness to endogenous opioids and the neuronal circuits that mediate them along with the multiplicity of estrogenic systems that concomitantly function in phase and out-of-phase with the reproductive cycle.
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It is essential that safe and effective treatment options be available to patients suffering from chronic pain. The emergence of an opioid epidemic has shaped public opinions and created stigmas surrounding the use of opioids for the management of pain. ⋯ We will also discuss the safety and efficacy of opioid and nonopioid treatment options for chronic pain. Finally, we will review the evidence for adenylyl cyclase type 1 (AC1) as a novel target for the treatment of chronic pain.