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Understanding Links among Opioid Use, Overdose, and Suicide.

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Safety of Opioids in Osteoarthritis: Outcomes of a Systematic Review and Meta-Analysis.

We aimed to assess the safety of opioids in the management of osteoarthritis (OA) in a systematic review and meta-analysis of randomized, placebo-controlled trials.

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Positron emission tomography imaging of endogenous mu-opioid mechanisms during pain and migraine.

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Volatile anaesthetics inhibit the thermosensitive nociceptor ion channel transient receptor potential melastatin 3 (TRPM3).

Volatile anaesthetics (VAs) are the most widely used compounds to induce reversible loss of consciousness and maintain general anaesthesia during surgical interventions. Although the mechanism of their action is not yet fully understood, it is generally believed, that VAs depress central nervous system functions mainly through modulation of ion channels in the neuronal membrane, including 2-pore-domain K+ channels, GABA and NMDA receptors. Recent research also reported their action on nociceptive and thermosensitive TRP channels expressed in the peripheral nervous system, including TRPV1, TRPA1, and TRPM8. Here, we investigated the effect of VAs on TRPM3, a less characterized member of the thermosensitive TRP channels playing a central role in noxious heat sensation.

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How has ziconotide impacted non-cancer pain management?

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The Blockade of CC Chemokine Receptor Type 1 Influences the Level of Nociceptive Factors and Enhances Opioid Analgesic Potency in a Rat Model of Neuropathic Pain.

A growing body of evidence has indicated that the release of nociceptive factors, such as interleukins and chemokines, by activated immune and glial cells has crucial significance for neuropathic pain generation and maintenance. Moreover, changes in the production of nociceptive immune factors are associated with low opioid efficacy in the treatment of neuropathy. Recently, it has been suggested that CC chemokine receptor type 1 (CCR1) signaling is important for nociception. Our study provides evidence that the development of hypersensitivity in rats following chronic constriction injury (CCI) of the sciatic nerve is associated with significant upregulation of endogenous CCR1 ligands, namely, CCL2, CCL3, CCL4, CCL6, CCL7 and CCL9 in the spinal cord and CCL2, CCL6, CCL7 and CCL9 in dorsal root ganglia (DRG). We showed that single and repeated intrathecal administration of J113863 (an antagonist of CCR1) attenuated mechanical and thermal hypersensitivity. Moreover, repeated administration of a CCR1 antagonist enhanced the analgesic properties of morphine and buprenorphine after CCI. Simultaneously, repeated administration of J113863 reduced the protein levels of IBA-1 in the spinal cord and MPO and CD4 in the DRG and, as a consequence, the level of pronociceptive factors, such as IL-1beta, IL-6, and IL-18. The obtained data provide evidence that CCR1 blockade reduces hypersensitivity and increases opioid-induced analgesia through the modulation of neuroimmune interactions.

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Opioid receptors mRNAs expression and opioids agonist-dependent G-protein activation in the rat brain following neuropathy.

Potent opioid-based therapies are often unsuccessful in promoting satisfactory analgesia in neuropathic pain. Moreover, the side-effects associated with opioid therapy are still manifested in neuropathy-like diseases, including tolerance, abuse, addiction and hyperalgesia, although the mechanisms underlying these effects remain unclear. Studies in the spinal cord and periphery indicate that neuropathy alters the expression of mu-[MOR], delta-[DOR] or kappa-[KOR] opioid receptors, interfering with their activity. However, there is no consensus as to the supraspinal opioidergic modulation provoked by neuropathy, the structures where the sensory and affective-related pain components are processed. In this study we explored the effect of chronic constriction of the sciatic nerve over 7 and 30 days (CCI-7d and CCI-30d, respectively) on MOR, DOR and KOR mRNAs expression, using in situ hybridization, and the efficacy of G-protein stimulation by DAMGO, DPDPE and U-69593 (MOR, DOR and KOR specific agonists, respectively), using [35S]GTPγS binding, within opioid-sensitive brain structures. After CCI-7d, CCI-30d or both, opioid receptor mRNAs expression was altered throughout the brain: MOR – in the paracentral/centrolateral thalamic nuclei, ventral posteromedial thalamic nuclei, superior olivary complex, parabrachial nucleus and posterodorsal tegmental nucleus; DOR – in the somatosensory cortex [SSC], ventral tegmental area, caudate putamen [CPu], nucleus accumbens [NAcc], raphe magnus [RMg] and PB; and KOR – in the locus coeruleus. Agonist-stimulated [35S]GTPγS binding was altered following CCI: MOR – CPu and RMg; DOR – prefrontal cortex [PFC], SSC, RMg and NAcc; and KOR -PFC and SSC. Thus, this study shows that several opioidergic circuits in the brain are recruited and modified following neuropathy.

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Vascular safety of erenumab for migraine prevention.

To examine the cardiovascular, cerebrovascular, and peripheral vascular safety of erenumab across migraine prevention studies.

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Chronic Pain and Opioid Use in Older People With HIV.

Chronic pain is common among older people with HIV. Etiologies of chronic pain are multifactorial in this population. A careful and thorough initial assessment of pain is important. Associated conditions that can contribute to pain should be explored and managed as indicated. Special consideration is warranted for some of the unique aspects of pain in people with HIV. Chronic pain management is multimodal; a variety of pharmacologic and nonpharmacologic strategies are effective. Among medications, opioids can be used but carry a risk of significant harms. The use and monitoring of opioids is discussed here, and recommendations are made for the safe prescribing of opioids for chronic pain.

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Mast cell stabilizer ketotifen fumarate reverses inflammatory but not neuropathic-induced mechanical pain in mice.

Mast cell (MC) activation could establish a positive feedback loop that perpetuates inflammation and maintains pain. Stabilizing MCs with ketotifen fumarate (KF) may disrupt this loop and relieve pain.

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