Articles: opioid.
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The Journal of physiology · Oct 2017
Chronic morphine reduces the readily releasable pool of GABA, a presynaptic mechanism of opioid tolerance.
Chronic treatment with opioids, such as morphine, leads to analgesic tolerance. While postsynaptic opioid tolerance is well documented, the involvement of presynaptic mechanisms remains unclear. We show that chronic morphine reduces the ability of periaqueductal grey (PAG) neurons to maintain GABAergic transmission. This depression of GABAergic transmission was due to a reduction in the effective size of the readily releasable pool. This also led to a reduction in opioid presynaptic inhibition; these presynaptic adaptations need to be considered in the development of strategies to reduce opioid tolerance. ⋯ The midbrain periaqueductal grey (PAG) plays a critical role in tolerance to the analgesic actions of opioids such as morphine. While numerous studies have identified the postsynaptic adaptations induced by chronic morphine treatment in this and other brain regions, the presence of presynaptic adaptations remains uncertain. We examined GABAergic synaptic transmission within rat PAG brain slices from animals which underwent a low dose morphine treatment protocol which produces tolerance, but not withdrawal. Evoked GABAergic IPSCs (inhibitory postsynaptic currents) were less in morphine compared to control saline treated animals. Postsynaptic GABAA receptor mediated currents and desensitization, presynaptic release probability (Pr ), and inhibition by endogenous neurotransmitters were similar in morphine and saline treated animals. By contrast, the effective size of the readily releasable pool (RRP) was smaller in morphine treated animals. While the μ-opioid agonist DAMGO produced a reduction in Pr and RRP size in saline treated animals, it only reduced Pr in morphine treated animals. Consequently, DAMGO-induced inhibition of evoked IPSCs during short burst stimulation was less in morphine, compared to saline treated animals. These results indicate that low dose chronic morphine treatment reduces presynaptic μ-opioid inhibition by reducing the size of the pool of vesicles available for action potential dependent release. This novel presynaptic adaptation may provide important insights into the development of efficacious pain therapies that can circumvent the development of opioid tolerance.
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The CDC Guideline for Prescribing Opioids for Chronic Pain, published last March, provided major steps toward bringing the medical community together to address the opioid epidemic in the U. S. However, the Guideline focuses primarily on treatment of new inductions into opioid therapy for pain. ⋯ Patients already maintained on opioids for chronic pain should not be subjected to abrupt cessation or rapid tapers, and the CDC's Guideline confirms this. Physicians should not balk from treating opioid-dependent patients with chronic pain, and the CDC's recommendations do contain helpful information if one reads through them carefully. This article attempts to distill the major points from the Guideline for the treatment of chronic-pain patients already on long-term opioid therapy.[Full article available at http://rimed.org/rimedicaljournal-2017-10.asp].
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New Rhode Island regulations require physicians and other licensed practitioners to make significant adjustments to comply with new requirements for prescribing narcotics for chronic pain. Responding to the opioid epidemic, the new rules are intended to improve patient safety by changing physicians' prescribing patterns. ⋯ The new regulations call upon physicians to make use of consultation services, which are also of limited availability. Although well intentioned, the new rules may contribute to treatment-access problems, and patients with chronic pain may resort to higher-risk "street" drugs when they are unable to access safe but effective medical treatment. [Full article available at http://rimed.org/rimedicaljournal-2017-10.asp].
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Review Meta Analysis
Association Between Opioid Use and Risk of Erectile Dysfunction: A Systematic Review and Meta-Analysis.
Opioid analgesics have been widely used to relieve chronic pain conditions; however, a connection between opioid analgesic administration and increased susceptibility to erectile dysfunction (ED) has been hypothesized. ⋯ Evidence from the included observational studies indicated that men with opioid use had a significantly increased risk of ED. Further randomized controlled trials are still needed to confirm this relation. Zhao S, Deng T, Luo L, et al. Association Between Opioid Use and Risk of Erectile Dysfunction: A Systematic Review and Meta-Analysis. J Sex Med 2017;14:1209-1219.
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Comment Letter
Reply to: Caution using the new "no pain no gain" approach.