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Effect of intrathecal morphine plus patient-controlled analgesia with morphine versus patient-controlled analgesia with morphine alone on total morphine dose 24 hours post-surgery: a systematic review.

The objective of this review was to evaluate the effects of preoperative intrathecal morphine (ITM) in addition to patient-controlled analgesia with morphine (PCAM) versus PCAM without preoperative ITM on total morphine dose in the first 24 hours postoperatively in adult patients undergoing abdominal or thoracic surgery.

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Enhanced mindfulness-based stress reduction in episodic migraine: a randomized clinical trial with magnetic resonance imaging outcomes.

We aimed to evaluate the efficacy of an enhanced mindfulness-based stress reduction (MBSR+) vs stress management for headache (SMH). We performed a randomized, assessor-blind, clinical trial of 98 adults with episodic migraine recruited at a single academic center comparing MBSR+ (n = 50) with SMH (n = 48). MBSR+ and SMH were delivered weekly by group for 8 weeks, then biweekly for another 8 weeks. The primary clinical outcome was reduction in headache days from baseline to 20 weeks. Magnetic resonance imaging (MRI) outcomes included activity of left dorsolateral prefrontal cortex (DLPFC) and cognitive task network during cognitive challenge, resting state connectivity of right dorsal anterior insula to DLPFC and cognitive task network, and gray matter volume of DLPFC, dorsal anterior insula, and anterior midcingulate. Secondary outcomes were headache-related disability, pain severity, response to treatment, migraine days, and MRI whole-brain analyses. Reduction in headache days from baseline to 20 weeks was greater for MBSR+ (7.8 [95% CI, 6.9-8.8] to 4.6 [95% CI, 3.7-5.6]) than for SMH (7.7 [95% CI 6.7-8.7] to 6.0 [95% CI, 4.9-7.0]) (P = 0.04). Fifty-two percent of the MBSR+ group showed a response to treatment (50% reduction in headache days) compared with 23% in the SMH group (P = 0.004). Reduction in headache-related disability was greater for MBSR+ (59.6 [95% CI, 57.9-61.3] to 54.6 [95% CI, 52.9-56.4]) than SMH (59.6 [95% CI, 57.7-61.5] to 57.5 [95% CI, 55.5-59.4]) (P = 0.02). There were no differences in clinical outcomes at 52 weeks or MRI outcomes at 20 weeks, although changes related to cognitive networks with MBSR+ were observed. Enhanced mindfulness-based stress reduction is an effective treatment option for episodic migraine.

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Dorsal Root Ganglion Stimulation Alleviates Pain-related Behaviors in Rats with Nerve Injury and Osteoarthritis.

Dorsal root ganglion field stimulation is an analgesic neuromodulation approach in use clinically, but its mechanism is unknown as there is no validated animal model for this purpose. The authors hypothesized that ganglion stimulation is effective in reducing pain-like behaviors in preclinical chronic pain models.

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Inflammatory cytokine expression in the skin of patients with postherpetic neuralgia.

To assess the expression of inflammatory cytokines in the affected and normal skin of postherpetic neuralgia (PHN) patients.

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Hippocampal glutamatergic synapses impairment mediated novel-object recognition dysfunction in rats with neuropathic pain.

Cognitive impairment is one of the most common complications associated with chronic pain. Almost 20% of chronic pain patients suffer from cognitive impairment, which may substantially influence their quality of life. Levels of major excitatory neurotransmitters in the central nervous system and alterations in the glutamatergic system may influence cognitive function and the pain sensory pathway. In this study, we adopted the spared nerve injury model to establish the progress of chronic pain and investigated the mechanism underlying the cognitive aspect related to it. At behavioral level, using the novel-object recognition test, mechanical hypersensitivity was observed in peripheral nerve-injured rats because they exhibited recognition deficits. We showed a dramatic decrease in hippocampal glutamate concentration using nuclear magnetic resonance and reduced glutamatergic synaptic transmission using whole-cell recordings. These were associated with deficient hippocampal long-term potentiation induced by high-frequency stimulation of the Schaffer collateral afferent. Ultra-high-performance liquid chromatography revealed lower levels of D-serine in the hippocampus of the spared nerve injury rats and that D-serine treatment could restore synaptic plasticity and cognitive dysfunction. The reduction of excitatory synapses was also increased by administering D-serine. These findings suggest that chronic pain has a critical effect on synaptic plasticity linked to cognitive function and may built up a new target for the development of cognitive impairment under chronic pain conditions.

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Altered mesocorticolimbic functional connectivity in chronic low back pain patients at rest and following sad mood induction.

Depressive symptoms are common among individuals with chronic pain. Previous work suggests that chronic pain patients have difficulty regulating emotional responses, which is a risk factor for the development of major depressive disorder (MDD). Function of the mesocorticolimbic system, a neural network associated with reward processing, contributes to emotion regulation. This network's dysfunction has been described in chronic pain and MDD research and potentially underlies the relationship among emotion dysregulation, chronic pain, and MDD development. Given that mood induction paradigms have been used to measure emotion regulation, the present study examined intrinsic mesocorticolimbic functional connectivity (FC) after induced sad mood in individuals with and without chronic low back pain (cLBP). Thirty-three MDD-free individuals (17 cLBP) underwent resting-state scanning before and after sad memory-evoked mood induction. A Group [cLBP, healthy control (HC)] x Mood (Neutral, Sadness) repeated measures ANCOVA was conducted on seed-based FC data using a mesolimbic a priori region of interest. Interaction effects were identified in the orbital frontal cortex and inferior frontal gyrus [F = 21.07, p < .05. h = .5]. Whereas cLBP showed significantly greater FC between these two regions and the mesolimbic seed under neutral mood, FC among these regions increased in HC and decreased in cLBP under sad mood. Exploratory graph theory analyses further describe between-group differences in mesocorticolimbic network properties. Findings support previous literature describing mesocorticolimbic dysfunction in cLBP and demonstrate aberrant function in emotion regulation. Mesocorticolimbic dysfunction during emotion regulation might contribute to the development of certain depressive phenotypes in chronic pain patients.

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Mechanism of Peripheral Nerve Stimulation in Chronic Pain.

With the advancement of technology, peripheral nerve stimulation (PNS) has been increasingly used to treat various chronic pain conditions. Its origin is based on the gate control theory postulated by Wall and Melzack in 1965. However, the exact mechanism behind PNS' analgesic effect is largely unknown. In this article, we performed a comprehensive literature review to overview the PNS mechanism of action.

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Physical disuse contributes to widespread chronic mechanical hyperalgesia, tactile allodynia, and cold allodynia through neurogenic inflammation and spino-parabrachio-amygdaloid pathway activation.

Physical disuse could lead to a state of chronic pain typified by complex regional pain syndrome type I due to fear of pain through movement (kinesiophobia) or inappropriate resting procedures. However, the mechanisms by which physical disuse is associated with acute/chronic pain and other pathological signs remain unresolved. We have previously reported that inflammatory signs, contractures, disuse muscle atrophy, spontaneous pain-like behaviors, and chronic widespread mechanical hyperalgesia based on central plasticity occurred after 2 weeks of cast immobilization in chronic post-cast pain (CPCP) rat model. In this study, we also demonstrated dystrophy-like changes, both peripheral nociceptive signals and activation of the central pain pathway in CPCP rats. This was done by the following methods: (1) vascular permeability (Evans blue dye) and inflammatory- and oxidative stress-related messenger RNA changes (real-time quantitative polymerase chain reaction); (2) immunofluorescence of pERK and/or c-Fos expression in the spino-parabrachio-amygdaloid pathway; and (3) blockade of nociceptive-related signals using sciatic nerve block. Furthermore, we demonstrated tactile allodynia using an optogenetic method in a transgenic rat line (W-TChR2V4), cold allodynia using the acetone test, and activation of dorsal horn neurons in the chronic phase associated with chronic mechanical hyperalgesia using c-Fos immunofluorescence. In addition, we showed that nociceptive signals in the acute phase are involved in chronic pathological pain-like behaviors by studying the effects of sciatic nerve block. Thus, we conclude that physical disuse contributes to dystrophy-like changes, spontaneous pain-like behavior, and chronic widespread pathological pain-like behaviors in CPCP rats after 2 weeks of cast immobilization.

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Assessing discrepancies in outcomes of pain rehabilitation: “these questionnaires don’t measure results that are relevant to me”.

Pain rehabilitation programs are recommended interventions for patients with chronic pain. Average effect sizes are moderate. Physiatrists, based on clinical experience, argue that the present outcome measures underestimate the outcome of pain rehabilitation programs.

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A Systematic Literature Review of Dorsal Root Ganglion Neurostimulation for the Treatment of Pain.

To conduct a systematic literature review of dorsal root ganglion (DRG) stimulation for pain.

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